University of Wisconsin Hematology

Multiple myeloma and other gammopathies; amyloidosis

Myeloma: general

  1. van de Donk et al. Multiple myeloma. Lancet 2021;397:410
  2. Palumbo et al. Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. J Clin Oncol 2015;33:2863
  3. Waxman et al. Racial disparities in incidence and outcome in multiple myeloma: a population-based study. Blood 2010;116:5501(Blacks had twofold higher incidence of myeloma, somewhat better survival than whites)
  4. Boise et al. The Tao of myeloma. Blood 2014;124:1873(The biologic basis for targeted therapy)
  5. Kuehl and Bergsagel. Early Genetic Events Provide the Basis for a Clinical Classification of Multiple Myeloma. Hematology 2005:346-352
  6. González et al. Immunoglobulin gene rearrangements and the pathogenesis of multiple myeloma. Blood 2007;110:3112
  7. Corre et al. Genetics of multiple myeloma: another heterogeneity level? Blood 2015;125:1870
  8. Landgren et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009; 113:5412(Increases in M-spike or free light chains preceded development of myeloma in only about half of cases)
  9. Weiss et al. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 2009;113:5418(Identifies a group with light chain-only “MGUS”)
  10. Terpos et al. Myeloma bone disease: from biology findings to treatment approaches. Blood 2019;133:1534
  11. Westhrin et al. Monoclonal immunoglobulins promote bone loss in multiple myeloma. Blood 2020;136:2656
  12. Tian et al. The Role of the Wnt-Signaling Antagonist DKK1 in the Development of Osteolytic Lesions in Multiple Myeloma. NEJM 2003;349:2483
  13. Nair et al. Clonal Immunoglobulin against Lysolipids in the Origin of Myeloma. NEJM 2016;374:555
  14. Terpos et al. Myeloma bone disease and proteasome inhibition therapies. Blood 2007;110:1098
  15. Hideshima et al. Advances in biology of multiple myeloma: clinical applications. Blood 2004;104:619
  16. Vachon et al. Increased risk of monoclonal gammopathy in first-degree relatives of patients with multiple myeloma or monoclonal gammopathy of undetermined significance. Blood 2009;114:785
  17. Landgren et al. Risk of plasma cell and lymphoproliferative disorders among 14621 first-degree relatives of 4458 patients with monoclonal gammopathy of undetermined significance in Sweden. Blood 2009;114:791(Increased risk of MGUS, myeloma, Waldenstroms and CLL)
  18. Landgren et al. Risk of monoclonal gammopathy of undetermined significance (MGUS) and subsequent multiple myeloma among African American and white veterans in the United States. Blood 2006;107:904(3-fold increased incidence of MGUS among African-Americans, with comparable increased incidence of myeloma)
  19. Brown et al. Risk of multiple myeloma and monoclonal gammopathy of undetermined significance among white and black male United States veterans with prior autoimmune, infectious, inflammatory, and allergic disorders. Blood 2008;111:3388(increased risk of myeloma or MGUS in people with autoimmune or other inflammatory conditions)
  20. Lindqvist et al. Personal and family history of immune-related conditions increase the risk of plasma cell disorders: a population-based study. Blood 2011;118:6284
  21. Rigolin et al. Neoplastic circulating endothelial cells in multiple myeloma with 13q14 deletion. Blood 2006;107:2531    (Evidence that circulating endothelial cells in myeloma may arise from neoplastic clone and contribute to tumor spread)
  22. Epstein et al. Markers of multiple hematopoietic-cell lineages in multiple myeloma. NEJM 1990; 322:664
  23. Bruns et al. Multiple myeloma–related deregulation of bone marrow–derived CD34+ hematopoietic stem and progenitor cells. Blood 2012;120:2620(Myeloma supresses hematopoietic stem cell function via an effect on the marrow microenvironment)
  24. Maia et al. Biological and clinical significance of dysplastic hematopoiesis in patients with newly diagnosed multiple myeloma. Blood 2020;135:2375
  25. Walker et al. Magnetic Resonance Imaging in Multiple Myeloma: Diagnostic and Clinical Implications. J Clin Oncol 2007;25:1121(MRI more sensitive than standard skeletal survey, better prognostic indicator)
  26. Ledergor et al. Single cell dissection of plasma cell heterogeneity in symptomatic and asymptomatic myeloma. Nat Med 2018;24:1867
  27. Fonseca et al.  Clinical and biologic implications of recurrent genomic aberrations in myeloma.  Blood 2003;101:4569(prognostic significance of cytogenetics in myeloma)
  28. Avet-Loiseau et al. Genetic abnormalities and survival in multiple myeloma: the experience of the Intergroupe Francophone du Myélome. Blood 2007;109:3489(t(4;14 and del(17p) are independent adverse risk factors)
  29. Schavgoulidze et al. Biallelic deletion of 1p32 defines ultra-high-risk myeloma, but monoallelic del(1p32) remains a strong prognostic factor. Blood 2023;141:1308
  30. Avet-Loiseau et al. Long-Term Analysis of the IFM 99 Trials for Myeloma: Cytogenetic Abnormalities [t(4;14), del(17p), 1q gains] Play a Major Role in Defining Long-Term Survival. J Clin Oncol 2012;30:1949
  31. Kumar et al. Trisomies in multiple myeloma: impact on survival in patients with high-risk cytogenetics. Blood 2012;119:2100(Trisomy amelorates adverse effects of “high-risk” cytogenetic markers)
  32. Goicoechea et al. Deep MRD profiling defines outcome and unveils different modes of treatment resistance in standard- and high-risk myeloma. Blood 2021;137:49 (Undetectable MRD after treatment predicts excellent prognosis even with high-risk cytogenetics)
  33. Kubicki et al. Mass spectrometry–based assessment of M protein in peripheral blood during maintenance therapy in multiple myeloma. Blood 2024;144:955
  34. Rasche et al. The presence of large focal lesions is a strong independent prognostic factor in multiple myeloma. Blood 2018;132:59
  35. Weber D. Solitary Bone and Extramedullary Plasmacytoma. Hematology 2005:373-376
  36. Yadav et al. Impact of cytogenetic abnormalities on the risk of disease progression in solitary bone plasmacytomas. Blood 2023;142:1871 (High-risk karyotype predicts rapid transition to myeloma)
  37. Ludwig et al. Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group. Blood 2008;111:4039
  38. Wadhera et al. Incidence, clinical course, and prognosis of secondary monoclonal gammopathy of undetermined significance in patients with multiple myeloma. Blood 2011;118:2985
  39. Brioli et al. Serum free immunoglobulin light chain evaluation as a marker of impact from intraclonal heterogeneity on myeloma outcome. Blood 2014;123:3414(New onset production of free light chain at time of relapse a marker for clonal evolution and worse prognosis)
  40. Dejoie et a. Serum free light chains, not urine specimens, should be used to evaluate response in light-chain multiple myeloma. Blood 2016;128:2941
  41. Munshi et al. Consensus recommendations for risk stratification in multiple myeloma: report of the International Myeloma Workshop Consensus Panel 2. Blood 2011; 117:4696
  42. Dimopoulos et al. Consensus recommendations for standard investigative workup: report of the International Myeloma Workshop Consensus Panel 3. Blood 2011;117:4701
  43. Dimopoulos et al. Role of Magnetic Resonance Imaging in the Management of Patients With Multiple Myeloma: A Consensus Statement. J Clin Oncol 2015;33:657(MRI preferred over plain films for early detection of bone disease)
  44. Mailankody et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood 2011;118:4086(11-fold increased risk in MM, 8-fold increase in MGUS)
  45. Zamagni et al. Imaging in multiple myeloma: How? When? Blood 2019;133:644
  46. Charalampous et al. Utility of PET/CT in assessing early treatment response in patients with newly diagnosed multiple myeloma. Blood Adv 2022;6:2763
  47. Bazarbachi et al. IgM-MM is predominantly a pre–germinal center disorder and has a distinct genomic and transcriptomic signature from WM. Blood 2021;138:1980
  48. Chakraborty et al. Abnormal metaphase cytogenetics predicts venous thromboembolism in myeloma: derivation and validation of the PRISM score. Blood 2022;140:2443
  49. Bertamini et al. High Levels of Circulating Tumor Plasma Cells as a Key Hallmark of Aggressive Disease in Transplant-Eligible Patients With Newly Diagnosed Multiple Myeloma. J Clin Oncol 2022;40:3120
  50. Garcés et al. Circulating Tumor Cells for the Staging of Patients With Newly Diagnosed Transplant-Eligible Multiple Myeloma. J Clin Oncol 2022;40:3151

Myeloma: treatment

  1. Perrot A. How I treat frontline transplantation-eligible multiple myeloma. Blood 2022;139:2882
  2. Zamagni et al. How I treat high-risk multiple myeloma.  Blood 2022;139:2889
  3. Facon et al. How I treat multiple myeloma in geriatric patients. Blood 2024;143:224
  4. 015;126:300Pawlyn and Davies. Toward personalized treatment in multiple myeloma based on molecular characteristics. Blood 2019;133:660
  5. Hoyos and Borrello The immunotherapy era of myeloma: monoclonal antibodies, vaccines, and adoptive T-cell therapies. Blood 2016;128:1679
  6. van de Donk et al. CD38 antibodies in multiple myeloma: back to the future. Blood 2018;131:13
  7. Moreau P. How I treat myeloma with new agents. Blood 2017;130:1507
  8. Gandolifi et al. How I treat the young patient with multiple myeloma. Blood 2018;132:1114
  9. Delforge and Ludwig. How I manage the toxicities of myeloma drugs. Blood 2017;129:2359
  10. Sonneveld et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood 2016;127:2955
  11. Banerjee et al. Dexamethasone dose intensity does not impact outcomes in newly diagnosed multiple myeloma: a secondary SWOG analysis. Blood 2025;145:75
  12. Palumbo et al. International Myeloma Working Group Consensus Statement for the Management, Treatment, and Supportive Care of Patients With Myeloma Not Eligible for Standard Autologous Stem-Cell Transplantation. J Clin Oncol 2014;32: 587
  13. Sonneveld et al. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. NEJM 2024;390:301 (2 year PFS increased from 68% to 84% by adding dara. With editorial)
  14. Stewart et al. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood 2015;126:1294(Similar efficacy, but less toxicity with lenalidomide vs thalidomide)
  15. Zweegman et al. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood 2016;127:1109 (Similar response rates; more neuropathy with thalidomide, more myelosuppression with lenalidomide)
  16. Jakubikova et al. Lenalidomide targets clonogenic side population in multiple myeloma: pathophysiologic and clinical implications. Blood 2011;117:4409
  17. Gay et al. Lenalidomide plus dexamethasone versus thalidomide plus dexamethasone in newly diagnosed multiple myeloma: a comparative analysis of 411 patients. Blood 2010; 115:1343 (Len/dex better tolerated and more effective than thal/dex)
  18. Benboubker et al. Lenalidomide and Dexamethasone in Transplant-Ineligible Patients with Myeloma. NEJM 2014;371:906(LD appears superior to MPT)
  19. Chanan-Khan et al. Activity and safety of bortezomib in multiple myeloma patients with advanced renal failure: a multicenter retrospective study. Blood 2007; 109:2604
  20. Rajkumar et al. Combination therapy with lenalidomide plus dexamethasone (Rev/Dex) for newly diagnosed myeloma. Blood 2005;106:4050(91% overall response rate)
  21. Facon et al. Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma. Blood 2018;131:301(Continuous Rev/Dex until disease progression superior to Rev/Dex x 72 weeks)
  22. Zonder et al. Lenalidomide and high-dose dexamethasone compared with dexamethasone as initial therapy for multiple myeloma: a randomized Southwest Oncology Group trial (S0232). Blood 2010;116:5838(Better response rates but more toxicity with lenalidomide; one-year survival not improved)
  23. Kapoor et al. Impact of risk stratification on outcome among patients with multiple myeloma receiving initial therapy with lenalidomide and dexamethasone. Blood 2009; 114:518(hypdiploidy, del[13q], del[17p], t[4;14] or t[14;16] associated with worse outcomes)
  24. Niesvizky et al. Lenalidomide-induced myelosuppression is associated with renal dysfunction: adverse events evaluation of treatment-naïve patients undergoing front-line lenalidomide and dexamethasone therapy. Br J Haematol 2007; 138:640
  25. Niesvizky et al. BiRD (Biaxin [clarithromycin]/Revlimid [lenalidomide]/dexamethasone) combination therapy results in high complete- and overall-response rates in treatment-naive symptomatic multiple myeloma. Blood 2008;111:1101(90% OR, 37% CR)
  26. Rossi et al. BiRd (clarithromycin, lenalidomide, dexamethasone): an update on long-term lenalidomide therapy in previously untreated patients with multiple myeloma. Blood 2013:121:1982(Median PFS 49 mo)
  27. Mulligan et al. Mutation of NRAS but not KRAS significantly reduces myeloma sensitivity to single-agent bortezomib therapy. Blood 2014;123:632
  28. Richardson et al. Single-Agent Bortezomib in Previously Untreated Multiple Myeloma: Efficacy, Characterization of Peripheral Neuropathy, and Molecular Correlations With Response and Neuropathy. J Clin Oncol 2009;27:3518(41% of patients had partial response or better)
  29. Bringhen et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood 2010;116:4745(Less neuropathy, roughly equivalent efficacy vs twice-weekly)
  30. Sonneveld et al. Bortezomib Induction and Maintenance Treatment in Patients With Newly Diagnosed Multiple Myeloma: Results of the Randomized Phase III HOVON-65/ GMMG-HD4 Trial. J Clin Oncol 2012;30:2946
  31. San Miguel et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. NEJM 2008;359:906(71% had PR or better, 30% had CR with improved survival vs controls getting MP only)
  32. San Miguel et al. Persistent Overall Survival Benefit and No Increased Risk of Second Malignancies With Bortezomib-Melphalan-Prednisone Versus Melphalan-Prednisone in Patients With Previously Untreated Multiple Myeloma. J Clin Oncol 2013;31:448
  33. Harousseau et al. Superior outcomes associated with complete response in newly diagnosed multiple myeloma patients treated with nonintensive therapy: analysis of the phase 3 VISTA study of bortezomib plus melphalan-prednisone versus melphalan-prednisone. Blood 2010;116:3743(VMP superior to MP)
  34. Richardson et al. Lenalidomide, bortezomib, and dexamethasone combination therapy in patients with newly diagnosed multiple myeloma. Blood 2010;116:679 (100% overall response rate)
  35. Cavo et al. Bortezomib with thalidomide plus dexamethasone compared with thalidomide plus dexamethasone as induction therapy before, and consolidation therapy after, double autologous stem-cell transplantation in newly diagnosed multiple myeloma: a randomised phase 3 study. Lancet 2010;376:2075
  36. Moreau et al. Bortezomib plus dexamethasone versus reduced-dose bortezomib, thalidomide plus dexamethasone as induction treatment before autologous stem cell transplantation in newly diagnosed multiple myeloma. Blood 2011;118:5752
  37. Rosiñol et al. Superiority of bortezomib, thalidomide, and dexamethasone (VTD) as induction pretransplantation therapy in multiple myeloma: a randomized phase 3 PETHEMA/GEM study. Blood 2012;120:1589
  38. Rosiñol et al. Bortezomib, lenalidomide, and dexamethasone as induction therapy prior to autologous transplant in multiple myeloma. Blood 2019;134:1337
  39. Sonneveld et al. Bortezomib-Based Versus Nonbortezomib-Based Induction Treatment Before Autologous Stem-Cell Transplantation in Patients With Previously Untreated Multiple Myeloma: A Meta-Analysis of Phase III Randomized, Controlled Trials. J Clin Oncol 2013;31:3279(Superior outcome with bortezomib-based regimens)
  40. Durie et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet 2017;389:519
  41. Attal et al. Lenalidomide, Bortezomib, and Dexamethasone with Transplantation for Myeloma. NEJM 2017;376:1311(RVD plus SCT superior to RVD alone; with editorial)
  42. Richardson et al. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. NEJM 2022;387:132 (RVD + ASCT prolonged RFS but not OS vs RVD alone )
  43. Ludwig et al. Randomized Phase II Study of Bortezomib, Thalidomide, and Dexamethasone With or Without Cyclophosphamide As Induction Therapy in Previously Untreated Multiple Myeloma. J Clin Oncol 2013;31:247(Equal efficacy, more toxicity with addting cyclophosphamide)
  44. Kumar et al. Randomized, multicenter, phase 2 study (EVOLUTION) of combinations of bortezomib, dexamethasone, cyclophosphamide, and lenalidomide in previously untreated multiple myeloma. Blood 2012;119:4375
  45. Reece DE. Posttransplantation Maintenance Therapy and Optimal Frontline Therapy in Myeloma. Hematology 2011:197
  46. Holstein et al. Updated analysis of CALGB (Alliance) 100104 assessing lenalidomide versus placebo maintenance after single autologous stem-cell transplantation for multiple myeloma: a randomised, double-blind, phase 3 trial. Lancet Haematol 2017;4:e431(Maintenance Rx improved median time to progression from 29 mo to 57 mo; more 2nd malignancies and cytopenias in lenalidomide group)
  47. Jakubowiak et al. Lenalidomide, bortezomib, pegylated liposomal doxorubicin, and dexamethasone in newly diagnosed multiple myeloma: a phase 1/2 Multiple Myeloma Research Consortium trial. Blood 2011;118:535(OR rate >90%, 29% CR)
  48. Morgan et al. Cyclophosphamide, thalidomide, and dexamethasone (CTD) as initial therapy for patients with multiple myeloma unsuitable for autologous transplantation. Blood 2011;118:1231(Better response rates, similar survival, more toxicity than melphalan/pred)
  49. Moreau et al. VTD is superior to VCD prior to intensive therapy in multiple myeloma: results of the prospective IFM2013-04 trial. Blood 2016;127:2569
  50. Palumbo et al. Bortezomib-Melphalan-Prednisone-Thalidomide Followed by Maintenance With Bortezomib-Thalidomide Compared With Bortezomib-Melphalan-Prednisone for Initial Treatment of Multiple Myeloma: Updated Follow-Up and Improved Survival. J Clin Oncol 2014;32: 634(Better 5 yr OS, more toxicity with addition of bortezomib)
  51. Morabito et al. Safety and efficacy of bortezomib-melphalan-prednisone-thalidomide followed by bortezomib-thalidomide maintenance (VMPT-VT) versus bortezomib-melphalan-prednisone (VMP) in untreated multiple myeloma patients with renal impairment. Blood 2011;118: 5759
  52. Jakubowiak et al. A phase 1/2 study of carfilzomib in combination with lenalidomide and low-dose dexamethasone as a frontline treatment for multiple myeloma. Blood 2012;120:1801
  53. Bringhen et al. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study. Blood 2014;124:63(2-yr PFS 76%)
  54. Sonneveld et al. Phase 2 study of carfilzomib, thalidomide, and dexamethasone as induction/consolidation therapy for newly diagnosed multiple myeloma. Blood 2015;125:449
  55. Jasielec et al. Carfilzomib, lenalidomide, and dexamethasone plus transplant in newly diagnosed multiple myeloma. Blood 2020;136:2513 (Stringent CR in 76%; 5 yr PFS 72%)
  56. Roussel et al. Up-front carfilzomib, lenalidomide, and dexamethasone with transplant for patients with multiple myeloma: the IFM KRd final results. Blood 2021;138:113
  57. Facon et al. Carfilzomib or bortezomib with melphalan-prednisone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood 2019;1953 (PFS similar in two arms)
  58. van de Donk et al. Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma. Blood 2016;127:681
  59. Mateos et a. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. NEJM 2018;378:518 (Adding dara increased 18 mo PFS from 50% to over 70%, increased CR rate from 74% to 91%)
  60. Facon et al. Daratumumab plus Lenalidomide and Dexamethasone for Untreated Myeloma. NEJM 2019;380:2104 (Adding dara increased CR rate from 25% to48% in transplant-ineligible patients; with editorial)
  61. Voorhees et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood 2020;136:936 (Adding dara improved CR rates and MRD negativity rates)
  62. Touzeau et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with tandem transplant for high-risk newly diagnosed myeloma. Blood 2024;143:2029 (Phase 2 study.  30 month PFS 80%)
  63. Yamamoto et al. Daratumumab in first-line therapy is cost-effective in transplant-eligible patients with newly diagnosed myeloma. Blood 2022;140:594
  64. Facon et al. Isatuximab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. NEJM 2024;391:1597
  65. Perrot et al. Measurable Residual Disease–Guided Therapy in Newly Diagnosed Myeloma. NEJM 2025;393:425 (ASCT may not be necessary in MRD-negative patients after quadruplet induction; with editorial)
  66. Chanan-Khan et al. Analysis of Herpes Zoster Events Among Bortezomib-Treated Patients in the Phase III APEX Study. J Clin Oncol 2008;26:4784 (Significant increase in risk of zoster with bortezomib treatment)
  67. Morgan et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 2012;119:7(Maintenance associated with significant improvement in PFS and OS)
  68. Ludwig et al. IMWG consensus on maintenance therapy in multiple myeloma. Blood 2012;119:3003
  69. Morgan et al. First-line treatment with zoledronic acid as compared with clodronic acid in multiple myeloma (MRC Myeloma IX): a randomised controlled trial. Lancet 2010;376:1989(Adding zolendronate to initial therapy improved overall and progression-free survival)
  70. Morgan et al. Effects of induction and maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX Trial. Blood 2012;119:5374(Zolendronate more effective than clodronate)
  71. Larocca et al. The impact of response on bone-directed therapy in patients with multiple myeloma. Blood 2013;122:2974(Patients in CR responded equally well to clodronate and zolendronate)
  72. McLaughlin and Alexanian. Myeloma protein kinetics following chemotherapy. Blood 1982; 60:851
  73. Chee et al. The importance of bone marrow examination in determining complete response to therapy in patients with multiple myeloma. Blood 2009;114:2617

Plasma cell leukemia

  1. van de Donk N. How We Manage Newly Diagnosed Multiple Myeloma With Circulating Tumor Cells. J Clin Oncol 2023;41:1342
  2. Royer et al. Bortezomib, Doxorubicin, Cyclophosphamide, Dexamethasone Induction Followed by Stem Cell Transplantation for Primary Plasma Cell Leukemia: A Prospective Phase II Study of the Intergroupe Francophone du Myélome. J Clin Oncol 2018;34:2125

Treatment of elderly patients

  1. Larocca and Palumbo. How I treat fragile myeloma patients. Blood 2015;126:2179
  2. Gay et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood 2011;117:3025
  3. Facon et al. Dexamethasone-based regimens versus melphalan-prednisone for elderly multiple myeloma patients ineligible for high-dose therapy. Blood 2006;107:1292 (Standard melphalan-prednisone superior to dexamethasone-containing regiments for older patients)
  4. Fayers et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 2011;118:1239(Addition of thalidomide to melphalan/pred extends median survival by about 20%)
  5. Palumbo et al. Oral melphalan, prednisone, and thalidomide in elderly patients with multiple myeloma: updated results of a randomized controlled trial. Blood 2008; 112:3107 (Better progression-free survival with MPT but no benefit for OS, perhaps because of better salvage Rx)
  6. Ludwig et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009;113:3435 (Response rates higher with TD than MP, but toxicity greater and overall survival worse)
  7. Mateos et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006;108:2165
  8. Offidani et al. Thalidomide, dexamethasone, and pegylated liposomal doxorubicin (ThaDD) for patients older than 65 years with newly diagnosed multiple myeloma. Blood 2006;108:2159
  9. Mateos et al. Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase 1/2 study. Blood 2006;108:2165
  10. Magarotto et al. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood 2016;127:1102(Adding cyclophosphamide or melphalan to lenalidomide-dex did not improve outcomes, was more toxic)
  11. Larocca et al. Dose/schedule-adjusted Rd-R vs continuous Rd for elderly, intermediate-fit patients with newly diagnosed multiple myeloma. Blood 2021;137:3027(Stopping steroids & reducing lenalidomide after 9 cycles less toxic, no less effective than continuing standard doses)
  12. Waage et al. Melphalan and prednisone plus thalidomide or placebo in elderly patients with multiple myeloma. Blood 2010;116:1405(Better response rate with thalidomide, but no improvement in PFS or OS)
  13. Palumbo et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. NEJM 2012;366:1759(Lenalidomide with MP, plus lenalidomide maintenance, prolonged PFS in patients 65-75 yo)
  14. Mateos et al. Maintenance therapy with bortezomib plus thalidomide or bortezomib plus prednisone in elderly multiple myeloma patients included in the GEM2005MAS65 trial. Blood 2012;120:2588(Maintenance therapy prolonged progression free survival with acceptable toxicity profile)
  15. Gay et al. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood 2013;122:1376(In patients 65-75 years old)
  16. Mateos et al. GEM2005 trial update comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators? Blood 2014;124:1887(Yes)
  17. Moreau et al. Phase 1/2 study of carfilzomib plus melphalan and prednisone in patients aged over 65 years with newly diagnosed multiple myeloma. Blood 2015;125:3100(Estimated 3 year OS 80%)
  18. Mateos et al. Sequential vs alternating administration of VMP and Rd in elderly patients with newly diagnosed MM. Blood 2016;127:420(High efficacy, “acceptable” toxicity, no difference between sequential and alternating schedules)
  19. Paiva et al. Minimal residual disease monitoring and immune profiling in multiple myeloma in elderly patients. Blood 2016;127:3165
  20. Facon et al. Oral ixazomib, lenalidomide, and dexamethasone for transplant-ineligible patients with newly diagnosed multiple myeloma. Blood 2021;137:3616(Adding ixazomib to Rd produces moderate benefit, no statistical difference in PFS)

Treatment of relapsed and refractory disease

  1. Kastritis et al. How I treat relapsed multiple myeloma. Blood 2022;139:2904
  2. Lee et al. BCMA- or GPRC5D-targeting bispecific antibodies in multiple myeloma: efficacy, safety, and resistance mechanisms. Blood 2024;143:1211
  3. Richardson et al.  A Phase 2 Study of Bortezomib in Relapsed, Refractory Myeloma. NEJM 2003;348:2609
  4. Richardson et al. Bortezomib or High-Dose Dexamethasone for Relapsed Multiple Myeloma.  NEJM 2005;352:2487(Bortezumib superior to dexamethasone)
  5. Richardson et al. Extended follow-up of a phase 3 trial in relapsed multiple myeloma: final time-to-event results of the APEX trial. Blood 2007;110:3557(Long-term results of above trial; extended bortezomib treatment appears beneficial)
  6. Orlowski et al. Randomized Phase III Study of Pegylated Liposomal Doxorubicin Plus Bortezomib Compared With Bortezomib Alone in Relapsed or Refractory Multiple Myeloma: Combination Therapy Improves Time to Progression. J Clin Oncol 2007;25:3892
  7. Glasmacher et al. A systematic review of phase-II trials of thalidomide monotherapy in patients with relapsed or refractory multiple myeloma. Br J Haematol 2006;132:584(30% CR or PR rate)
  8. Richardson et al. Safety and efficacy of single-agent lenalidomide in patients with relapsed and refractory multiple myeloma. Blood 2009;114:772 (26% had CR or PR)
  9. Dimopoulos et al. Lenalidomide plus Dexamethasone for Relapsed or Refractory Multiple Myeloma. NEJM 2007;357:2123
  10. Wang et al. Lenalidomide plus dexamethasone is more effective than dexamethasone alone in patients with relapsed or refractory multiple myeloma regardless of prior thalidomide exposure. Blood 2008;112:4445
  11. Weber et al. Lenalidomide plus Dexamethasone for Relapsed Multiple Myeloma in North America. NEJM 2007;357:2133
  12. Richardson et al. A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood 2014;123:1461
  13. Nijhof et al. Phase 1/2 study of lenalidomide combined with low-dose cyclophosphamide and prednisone in lenalidomide-refractory multiple myeloma. Blood 2016;128:2297(Over 80% had some response, median PFS 12 mo)
  14. Palumbo et al. Bortezomib, melphalan, prednisone, and thalidomide for relapsed multiple myeloma. Blood 2007;109:2767
  15. Reece et al. Phase I-II Trial of Bortezomib Plus Oral Cyclophosphamide and Prednisone in Relapsed and Refractory Multiple Myeloma. J Clin Oncol 2008;26:4777(95% overall response rate, over 50% CR)
  16. Harrison et al. A high rate of durable responses with romidepsin, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma. Blood 2011;118:6274
  17. Vij et al. An open-label, single-arm, phase 2 (PX-171-004) study of single-agent carfilzomib in bortezomib-naive patients with relapsed and/or refractory multiple myeloma. Blood 2012;119:5661
  18. Wang et al. Phase 2 dose-expansion study (PX-171-006) of carfilzomib, lenalidomide, and low-dose dexamethasone in relapsed or progressive multiple myeloma. Blood 2013;122:3122(OR rate 77%)
  19. Berenson et al. CHAMPION-1: a phase 1/2 study of once-weekly carfilzomib and dexamethasone for relapsed or refractory multiple myeloma. Blood 2015;127:3360(OR rate 77%, median PFS 12.6 mo)
  20. Dimopolous et al. Carfilzomib, dexamethasone, and daratumumab versus carfilzomib and dexamethasone for patients with relapsed or refractory multiple myeloma (CANDOR): results from a randomised, multicentre, open-label, phase 3 study. Lancet 2020;396:186
  21. Knop et al. Lenalidomide, adriamycin, and dexamethasone (RAD) in patients with relapsed and refractory multiple myeloma: a report from the German Myeloma Study Group DSMM (Deutsche Studiengruppe Multiples Myelom). Blood 2009;113:4137(73% OR rate)
  22. Alsina et al. Farnesyltransferase inhibitor tipifarnib is well tolerated, induces stabilization of disease, and inhibits farnesylation and oncogenic/tumor survival pathways in patients with advanced multiple myeloma.  Blood 2004;103:3271
  23. Lacy et al. Pomalidomide plus low-dose dexamethasone in myeloma refractory to both bortezomib and lenalidomide: comparison of 2 dosing strategies in dual-refractory disease. Blood 2011;118:2970
  24. Richardson et al. Phase 1 study of pomalidomide MTD, safety, and efficacy in patients with refractory multiple myeloma who have received lenalidomide and bortezomib. Blood 2013;121:1961
  25. Leleu et al. Pomalidomide plus low-dose dexamethasone is active and well tolerated in bortezomib and lenalidomide–refractory multiple myeloma: Intergroupe Francophone du Myélome 2009-02. Blood 2013;121:1968
  26. Dimopoulos et al. Safety and efficacy of pomalidomide plus low-dose dexamethasone in STRATUS (MM-010): a phase 3b study in refractory multiple myeloma. Blood 2016;128:497
  27. Leleu et al. Pomalidomide plus low-dose dexamethasone in multiple myeloma with deletion 17p and/or translocation (4;14): IFM 2010-02 trial results. Blood 2015;125:1411
  28. Larocca et al. Pomalidomide, cyclophosphamide, and prednisone for relapsed/refractory multiple myeloma: a multicenter phase 1/2 open-label study. Blood 2013;122:2799
  29. Richardson et al. Pomalidomide alone or in combination with low-dose dexamethasone in relapsed and refractory multiple myeloma: a randomized phase 2 study. Blood 2014;123:1826
  30. Baz et al. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood 2016;127:2561(This regimen superior to Pom/dex in lenalidomide-refractory disease)
  31. Garderet et al. Pomalidomide, cyclophosphamide, and dexamethasone for relapsed multiple myeloma. Blood 2018;132:2555
  32. Paludo et al. Pomalidomide, bortezomib, and dexamethasone for patients with relapsed lenalidomide-refractory multiple myeloma. Blood 2017;130:1198(86% OR rate)
  33. Lentzsch et al. Combination of bendamustine, lenalidomide, and dexamethasone (BLD) in patients with relapsed or refractory multiple myeloma is feasible and highly effective: results of phase 1/2 open-label, dose escalation study. Blood 2012;119:4608 (75% had PR, 93% OS at 1 yr)
  34. Ludwig et al. Bendamustine-bortezomib-dexamethasone is an active and well-tolerated regimen in patients with relapsed or refractory multiple myeloma. Blood 2014;123:985
  35. Siegel et al. A phase 2 study of single-agent carfilzomib (PX-171-003-A1) in patients with relapsed and refractory multiple myeloma. Blood 2012;120:2817
  36. Lonial et al. Elotuzumab in Combination With Lenalidomide and Low-Dose Dexamethasone in Relapsed or Refractory Multiple Myeloma. J Clin Oncol 2012;30:1953
  37. Jakubowiak et al. Phase I Trial of Anti-CS1 Monoclonal Antibody Elotuzumab in Combination With Bortezomib in the Treatment of Relapsed/Refractory Multiple Myeloma. J Clin Oncol 2012;30:1960
  38. Lonial et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. NEJM 2015;373:621(Adding elotuzumab to len/dex decreased risk of progression or death by 30% at 2 yr)
  39. Jakubowiak et al. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood 2016;127:2833(Adding elotuzumab prolongs median PFS from 6.9 mo to 9.7 mo with minimal toxicity)
  40. Dimopoulos et al. Elotuzumab plus Pomalidomide and Dexamethasone for Multiple Myeloma. NEJM 2018;379:1811(ELO doubled response rate and increased median PFS from 4.7 mo to 10.3 mo)
  41. Stewart et al. Carfilzomib, Lenalidomide, and Dexamethasone for Relapsed Multiple Myeloma. NEJM 2015;372:142(Improved OS and OR rates with addition of carfilzomib to Rev/Dex)
  42. Siegel et al. Improvement in Overall Survival With Carfilzomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol 2018;36:728(Adding carfilzomib to LD improved median OS from 40 to 48 mo)
  43. Shah et al. Carfilzomib, pomalidomide, and dexamethasone for relapsed or refractory myeloma. Blood 2015;126:2284(50% overall response rate in this group of lenalidomide-resistant patients; regimen “well-tolerated”)
  44. Avet-Loiseau et al. Carfilzomib significantly improves the progression-free survival of high-risk patients in multiple myeloma. Blood 2016;128:1174(KRd vs Rd for relapsed disease; markedly better outcomes with KRd)
  45. Dimopoulos et al. Carfilzomib vs bortezomib in patients with multiple myeloma and renal failure: a subgroup analysis of ENDEAVOR. Blood 2019;133:147(Better PFS and OS with carfilzomib/dex vs Vd)
  46. Moreau et al. Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. NEJM 2016;374:1621(Addition of ixazomib to LD prolonged PFS by about 50%)
  47. Richardson et al. Final Overall Survival Analysis of the TOURMALINE-MM1 Phase III Trial of Ixazomib, Lenalidomide, and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma. J Clin Oncol 2021;39:2430 (Adding ixazomib did not improve OS in above trial)
  48. Kumar et al. Randomized phase 2 trial of ixazomib and dexamethasone in relapsed multiple myeloma not refractory to bortezomib. Blood 2016;128:2415
  49. Avet-Loiseau et al. Ixazomib significantly prolongs progression-free survival in high-risk relapsed/refractory myeloma patients. Blood 2017;130:2610
  50. Moreau et a. Promising efficacy and acceptable safety of venetoclax plus bortezomib and dexamethasone in relapsed/refractory MM. Blood 2017;130:2392
  51. Kumar et al. Efficacy of venetoclax as targeted therapy for relapsed/refractory t(11;14) multiple myeloma. Blood 2017;130:2401
  52. Richardson et al. Phase 1 study of marizomib in relapsed or relapsed and refractory multiple myeloma: NPI-0052-101 Part 1. Blood 2016;127:2693
  53. Richardson et al. Panobinostat plus bortezomib and dexamethasone in previously treated multiple myeloma: outcomes by prior treatment. Blood 2016;127:713
  54. Kumar et al. Dinaciclib, a novel CDK inhibitor, demonstrates encouraging single-agent activity in patients with relapsed multiple myeloma. Blood 2015;125:443
  55. Lokhorst et al. Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma. NEJM 2015;373:1207(with editorial)
  56. Usmani et al. Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma. Blood 2016;128:37(31% response rate, some deep/durable responses)
  57. Lonial et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet 2016;387:1551(30% OR rate)
  58. Usmani et al Subcutaneous delivery of daratumumab in relapsed or refractory multiple myeloma. Blood 2019;134:668
  59. Dimopoulos et al. Daratumumab, Lenalidomide, and Dexamethasone for Multiple Myeloma. NEJM 2016;375:1319(12 mo PFS 83% vs 60%, CR 43% vs 19% favoring dara group)
  60. Palumbo et al. Daratumumab, Bortezomib, and Dexamethasone for Multiple Myeloma. NEJM 2016;375:754(Adding daratumumab improved 12 mo PFS from 27% to 61%)
  61. Plesner et al. Phase 1/2 study of daratumumab, lenalidomide, and dexamethasone for relapsed multiple myeloma. Blood 2016;128:1821(OR rate 81%, CR rate 25%, 18 mo PFS 72%)
  62. Chari et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood 2017;130:974
  63. Chari et al. Daratumumab plus carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma. Blood 2019;134:421(ORR 84%, 12 mo PFS 74%)
  64. Chapuy et al. Resolving the daratumumab interference with blood compatibility testing. Transfusion 2015;33:1545
  65. Martin et al. A phase 1b study of isatuximab plus lenalidomide and dexamethasone for relapsed/refractory multiple myeloma. Blood 2017;129:3294
  66. Dimopoulos et al. Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma. Blood 2021;137:1154
  67. Attal et al. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet 2019;394:2096
  68. Moreau et al. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet 2021;397:2361
  69. Badros et al. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood 2017;130:1189
  70. Vogl et al. Selective Inhibition of Nuclear Export With Oral Selinexor for Treatment of Relapsed or Refractory Multiple Myeloma. J Clin Oncol 2018;36:859
  71. Chen et al. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. Blood 2018;131:855
  72. Bahlis et al. Selinexor plus low-dose bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma. Blood 2018;132:2546
  73. Grosicki et al. Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial. Lancet 2020;396:1563
  74. Richardson et al. Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. NEJM 2023;379:1009 (With editorial)
  75. Moreau et al. Teclistamab in Relapsed or Refractory Multiple Myeloma. NEJM 2022;387:495 (40% CR rate, 27% MRD-negative; with editorial)
  76. Usmani et al. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet 2021;398:665
  77. Touzeau et al. Efficacy and safety of teclistamab in patients with relapsed/refractory multiple myeloma after BCMA-targeting therapies. Blood 2024;144:2375
  78. Ailawadhi et al. Ide-cel vs standard regimens in triple-class–exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses. Blood 2024;144:2389 (Teclistamab)
  79. Chari et al. Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. NEJM 2022;387:2232 (> 60% response rate)
  80. Cohen et al. Talquetamab plus Teclistamab in Relapsed or Refractory Multiple Myeloma. NEJM 2025;392:138
  81. Bahlis et al. Elranatamab in relapsed or refractory multiple myeloma: the MagnetisMM-1 phase 1 trial. Nat Med 2023;29:2570
  82. Trudel et al. Belantamab mafodotin, pomalidomide and dexamethasone in refractory multiple myeloma: a phase 1/2 trial. Nat Med 2024;30:543
  83. Hungria et al. Belantamab Mafodotin, Bortezomib, and Dexamethasone for Multiple Myeloma. NEJM 2024;391:393 (With editorial)
  84. Dimopoulos et al. Belantamab Mafodotin, Pomalidomide, and Dexamethasone in Multiple Myeloma. NEJM 2024;391:408 (With editorial)
  85. Vogt et al. Targeted interferon therapy with modakafusp alfa for relapsed or refractory multiple myeloma. Blood 2025;145:944

CAR T-cells in myeloma

  1. Garfall et al. Chimeric Antigen Receptor T Cells against CD19 for Multiple Myeloma. NEJM 2015;373:1040(Single case report; patient received CAR cells after auto-HSCT, had durable CR despite very low level of CD19 expression on myeloma cells)
  2. Ali et al. T cells expressing an anti–B-cell maturation antigen chimeric antigen receptor cause remissions of multiple myeloma. Blood 2016;128:1688
  3. Mikkilineni and Kochenderfer. Chimeric antigen receptor T-cell therapies for multiple myeloma. Blood 2017;130:2594
  4. Raje et al. Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma. NEJM 2019;380:1726
  5. Munshi et al. Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. NEJM 2021;384:705(Median PFS 8.8 mo, 26% became MRD-negative)
  6. Mailankody et al. GPRC5D-Targeted CAR T Cells for Myeloma. NEJM 2022;387:1196
  7. Rodriguez-Otero et al. Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma. NEJM 2023;388:1002 (39% CR rate vs 5% with standard care, PFS rate 13.3 mo vs 4 mo)
  8. Standard-of-care idecabtagene vicleucel for relapsed/refractory multiple myeloma. Blood 2025;146:167
  9. San-Miguel et al. Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. NEJM 2023;389:335 (73% CR vs 22% with standard care; moderately toxic)
  10. Cohen et al. Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents. Blood 2023;141:219
  11. Berdeja et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet 2021;398:314
  12. Sidana et al. Safety and efficacy of standard-of-care ciltacabtagene autoleucel for relapsed/refractory multiple myeloma. Blood 2025;145:85
  13. Tuazon et al. A phase 1 trial of fully human BCMA CAR-T therapy for relapsed/refractory multiple myeloma with 5-year follow-up. Blood 2025;146:535

Myeloma: marrow and stem cell transplantation

Myeloma: complications and supportive care

  1. Berenson et al. Efficacy of pamidronate in reducing skeletal events in patients with advanced multiple myeloma. NEJM 1996;334:488
  2. Terpos et al. Optimal use of bisphosphonates in patients with multiple myeloma. Blood 2013;121:3325
  3. Mehrotra and Ruggiero. Bisphosphonate Complications Including Osteonecrosis of the Jaw. Hematology 2006;356
  4. Woo et al. Systematic Review: Bisphosphonates and Osteonecrosis of the Jaws. Ann Intern Med 2006;10:753
  5. Ludwig et al. Erythropoietin treatment of anemia associated with multiple myeloma. NEJM 1990; 322:1693
  6. Chapel et al. Randomized trial of intravenous immunoglobulin as prophylaxis against infection in plateau-phase multiple myeloma. Lancet 1994;343:1059
  7. Heher et al. Kidney disease associated with plasma cell dyscrasias. Blood 2010;116:1397
  8. Clark et al. Plasma Exchange When Myeloma Presents as Acute Renal Failure. A Randomized, Controlled Trial. Ann Intern Med 2005;143:777 (No apparent benefit from plasma exchange)
  9. Burnette et al. Renal Improvement in Myeloma with Bortezomib plus Plasma Exchange (letter). NEJM 2011;364:2365(86% CR or PR rate)
  10. Ludwig et al. Light Chain–Induced Acute Renal Failure Can Be Reversed by Bortezomib-Doxorubicin-Dexamethasone in Multiple Myeloma: Results of a Phase II Study. J Clin Oncol 210;28:4635
  11. Royal et al. Clinicopathologic predictors of renal outcomes in light chain cast nephropathy: a multicenter retrospective study. Blood 2020;135:1833
  12. Li et al. Cardiovascular complications of novel multiple myeloma treatments. Circulation 2016;133:908
  13. Eby C. Bleeding and thrombosis risks in plasma cell dyscrasias. Hematology 2007:158
  14. Carrier et al. Rates of venous thromboembolism in multiple myeloma patients undergoing immunomodulatory therapy with thalidomide or lenalidomide: a systematic review and meta-analysis. J Thromb Haemost 2011;9:653(Therapeutic dose of warfarin most effective in VTE prevention)
  15. Leleu et al. MELISSE, a large multicentric observational study to determine risk factors of venous thromboembolism in patients with multiple myeloma treated with immunomodulatory drugs. Thromb Haemost 2013;110:844(VTE occurred in 7% on ASA, 3% on LWMH, 0% on VKA)
  16. Libourel et al. High incidence of arterial thrombosis in young patients treated for multiple myeloma: results of a prospective cohort study. Blood 2010;116:22(Smoking, hypertension, and high factor VIII levels associated with higher risk. Highest incidence during induction Rx)
  17. Kristinsson et al. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 2008;112:3582(risk of DVT 3-fold higher than normal in MGUS and 9-fold higher in myeloma)
  18. Kristinsson et al. Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population-based study. Blood 2010;115:4991 (Risk of venous events greater than risk of arterial events in both conditions)
  19. Larocca et al. Aspirin or enoxaparin thromboprophylaxis for patients with newly diagnosed multiple myeloma treated with lenalidomide. Blood 2012;119:933(VTE rates 2.3% with ASA vs 1.2% with LMWH)
  20. Palumbo et al. Aspirin, Warfarin, or Enoxaparin Thromboprophylaxis in Patients With Multiple Myeloma Treated With Thalidomide: A Phase III, Open-Label, Randomized Trial. J Clin Oncol 2011;29:986(All three drugs had similar efficacy)
  21. Bradbury et al. Thrombosis in patients with myeloma treated in the Myeloma IX and Myeloma XI phase 3 randomized controlled trials. Blood 2020;136:1091(Thrombotic risk high with immunomodulatory therapy, prophylaxis not very effective)
  22. Argyriou et al. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood 2008; 112:1593
  23. Thomas et al. Second malignancies after multiple myeloma: from 1960s to 2010s. Blood 2012;119:2731
  24. Usmani et al. Risk factors for MDS and acute leukemia following total therapy 2 and 3 for multiple myeloma. Blood 2013;121:4753
  25. Dimopoulos et al. A review of second primary malignancy in patients with relapsed or refractory multiple myeloma treated with lenalidomide. Blood 2012;119:2764 (Incidence rate of invasive cancer 2 per 100 patient-years)

MGUS & Smoldering myeloma

  1. Mouhieddine et al. Monoclonal gammopathy of undetermined significance. Blood 2019;133:2484
  2. El-Khoury et al. Prevalence of monoclonal gammopathies and clinical outcomes in a high-risk US population screened by mass spectrometry: a multicentre cohort study.  Lancet Haematol 2022;9:e340 (Mass spec found MG in 43% of a high risk population, vs 6% with SPEP/iFix)
  3. Bertamini et al. Serum free light chains in a racially diverse population including African Americans and populations from South Africa. Blood 2025;145:840 (Conventional FLC ratios over-diagnose MGUS in Black individuals)
  4. Go and Rajkumar. How I manage monoclonal gammopathy of undetermined significance. Blood 2018;131:163
  5. Kyle et al. Long-Term Follow-up of Monoclonal Gammopathy of Undetermined Significance. NEJM 2018;378:241(Risk of progression about 1%/yr; skewed free light chain ratio and larger M-spike associated with higher progression risk)
  6. Korde et al. Monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM): novel biological insights and development of early treatment strategies. Blood 2011;117:5573
  7. Weinhold et al. Inherited genetic susceptibility to monoclonal gammopathy of unkown significance. Blood 2014;123:2513
  8. Rajkumar et al. Advances in the Diagnosis, Classification, Risk Stratification, and Management of Monoclonal Gammopathy of Undetermined Significance: Implications for Recategorizing Disease Entities in the Presence of Evolving Scientific Evidence. Mayo Clin Proc 2010;85:945
  9. Visram et al. Comparison of progression risk of monoclonal gammopathy of undetermined significance by method of detection. Blood 2025;145:325 (Routine screening for MGUS does not improve outcomes)
  10. Eythorsson et al. Development of a Multivariable Model to Predict the Need for Bone Marrow Sampling in Persons With Monoclonal Gammopathy of Undetermined Significance: A Cohort Study Nested in a Clinical Trial. Ann Intern Med 2024;177:449
  11. Campbell et al. Response comparison of multiple myeloma and monoclonal gammopathy of undetermined significance to the same anti-myeloma therapy: a retrospective cohort study. Lancet Haematol 2017;4:e584(Suggests that MGUS clones tend to be less responsive to chemotherapy than myeloma clones)
  12. Bianchi et al. Impact of optimal follow-up of monoclonal gammopathy of undetermined significance on early diagnosis and prevention of myeloma-related complications. Blood 2010;116:2019(“Routine annual follow-up may not be required in low-risk MGUS”)
  13. Sigurdardottir et al. The Role of Diagnosis and Clinical Follow-up of Monoclonal Gammopathy of Undetermined Significance on Survival in Multiple Myeloma. JAMA Oncol 2015;1:168(Prior MGUS diagnosis associated with better survival; due to regular monitoring and earlier detecton? With editorial)
  14. Landgren et al. Association of Immune Marker Changes With Progression of Monoclonal Gammopathy of Undetermined Significance to Multiple Myeloma. JAMA Oncol 2019;5:1293
  15. Kyle et al. Prevalence of monoclonal gammopathy of undetermined significance.  NEJM 2006;354:1362 (MGUS found in 3.2% of those 50 or older, and in 5.3% of those 70 or older)
  16. Wadhera and Rajkumar. Prevalence of Monoclonal Gammopathy of Undetermined Significance: A Systematic Review. Mayo Clin Proc 2010;85:933
  17. Turesson et al. Monoclonal gammopathy of undetermined significance and risk of lymphoid and myeloid malignancies: 728 cases followed up to 30 years in Sweden. Blood 2014;123:338(0.5%/yr incidence of myeloma; M-spike > 1.5 g/dL, skewed free light chain ratio, suppression of normal Ig production predicted myeloma development)
  18. Greenberg et al. Familial monoclonal gammopathy of undetermined significance and multiple myeloma: epidemiology, risk factors, and biological characteristics. Blood 2012;119;5359
  19. Iwanaga et al. Relationship between monoclonal gammopathy of undetermined significance and radiation exposure in Nagasaki atomic bomb survivors. Blood 2009;113:1639
  20. Landgren et al. Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study. Blood 2009;113:6386(prevalence of MGUS doubled after working with pesticides)
  21. Landgren et al. Monoclonal gammopathy of undetermined significance (MGUS) consistently precedes multiple myeloma: a prospective study. Blood 2009; 113:5412(Increases in M-spike or free light chains preceded development of myeloma in only about half of cases)
  22. Weiss et al. A monoclonal gammopathy precedes multiple myeloma in most patients. Blood 2009;113:5418(Identifies a group with light chain-only “MGUS”)
  23. Kyle et al. A long-term study of prognosis in monoclonal gammopathy of undetermined significance. NEJM 2002;346:564
  24. Baldini et al. Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy. Blood 1996;87:912
  25. Avet-Loiseau and Bahlis. Smoldering multiple myeloma: taking the narrow over the wide path?. Blood 2024;143:2025 (Advocates against treating SMM)
  26. Vaxman and Gertz. How I approach smoldering multiple myeloma. Blood 2022;140:828
  27. Rajkumar et al. Smoldering multiple myeloma. Blood 2015;125:3069
  28. Dispenzieri et al. Immunoglobulin free light chain ratio is an independent risk factor for progression of smoldering (asymptomatic) multiple myeloma. Blood 2008;111:785
  29. Kyle et al. Clinical course and prognosis of smoldering (asymptomatic) multiple myeloma. NEJM 2007;356:2582
  30. Barlogie et al. Seven-year median time to progression with thalidomide for smoldering myeloma: partial response identifies subset requiring earlier salvage therapy for symptomatic disease. Blood 2008;112;3122
  31. Neben et al. Progression in Smoldering Myeloma Is Independently Determined by the Chromosomal Abnormalities del(17p), t(4;14), Gain 1q, Hyperdiploidy, and Tumor Load . J Clin Oncol 2013; 31:4325
  32. Dimopoulos et al. Daratumumab or Active Monitoring for High-Risk Smoldering Multiple Myeloma. NEJM 2025;392:1777 (Modest improvement in overall survival with daratumumab; with editorial)
  33. Landgren et al. Efficacy and safety of daratumumab in intermediate/high-risk smoldering multiple myeloma: final analysis of CENTAURUS. Blood 2025;145:1658
  34. Mateos et al. Lenalidomide plus dexamethasone for high-risk smoldering multiple myeloma. NEJM 2013;369:438
  35. Dispenzieri et al. Smoldering multiple myeloma requiring treatment: time for a new definition? Blood 2013;122:4172
  36. Paiva et al. Immune status of high-risk smoldering multiple myeloma patients and its therapeutic modulation under LenDex: a longitudinal analysis. Blood 2016;127:1151(LenDex appeared to improve immune function in SM)
  37. Ng et al. Bone microstructural changes revealed by high-resolution peripheral quantitative computed tomography imaging and elevated DKK1 and MIP-1α levels in patients with MGUS. Blood 2011;118:6529(Cytokine-mediated altered bone microstructure in MGUS)
  38. Farr et al. Altered cortical microarchitecture in patients with monoclonal gammopathy of undetermined significance. Blood 2014;123:647(May explain increased fracture risk in this condition)
  39. Kristinsson et al. Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study. Blood 2010;116:2651(Increased fracture risk in axial bones)
  40. Kristinsson et al. Deep vein thrombosis after monoclonal gammopathy of undetermined significance and multiple myeloma. Blood 2008;112:3582(risk of DVT 3-fold higher than normal in MGUS and 9-fold higher in myeloma)
  41. Fermand et al. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood 2018;132:1478(Reviews various conditions associated with monoclonal gammopathy that cause organ damage or other disease)
  42. Sverrisdottir et al. Association Between Autoimmune Diseases and Monoclonal Gammopathy of Undetermined Significance: An Analysis From a Population-Based Screening Study. Ann Intern Med 2024;177:711 (No association found)
  43. Mailankody et al. Risk of acute myeloid leukemia and myelodysplastic syndromes after multiple myeloma and its precursor disease (MGUS). Blood 2011;118:4086(11-fold increased risk in MM, 8-fold increase in MGUS)
  44. Jónsdóttir et al. Approaching hypercalcemia in monoclonal gammopathy of undetermined significance: insights from the iStopMM screening study. Blood 2025;145:970 (Hypercalcemia in the absence of other indicators of progression is usually not due to myeloma)

Waldenstrom’s macroglobulinemia/IgM gammopathy

  1. Kapoor et al. Diagnosis and Management of Waldenström Macroglobulinemia Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines 2016. JAMA Oncol 2017;3:1257
  2. Dimopoulos and Kastritis. How I treat Waldenström macroglobulinemia. Blood 2019;134:2022
  3. Gertz M. Waldenstrom Macroglobulinemia: Tailoring Therapy for the Individual. J Clin Oncol 2022;40:2600
  4. Treon et al. How I use genomics and BTK inhibitors in the treatment of Waldenström macroglobulinemia. Blood 2024;143:1702
  5. Castillo et al. Recommendations for the diagnosis and initial evaluation of patients with Waldenström Macroglobulinaemia: A Task Force from the 8th International Workshop on Waldenström Macroglobulinaemia. Br J Haem 2016;175:77
  6. Leblond et al. Treatment recommendations from the Eighth International Workshop on Waldenström’s Macroglobulinemia. Blood 2016;128:1321
  7. Ansell et al. Diagnosis and Management of Waldenström Macroglobulinemia: Mayo Stratification of Macroglobulinemia and Risk-Adapted Therapy (mSMART) Guidelines. Mayo Clin Proc 2010;85:824
  8. Morel et al. International prognostic scoring system for Waldenström macroglobulinemia. Blood 2009;113:4163(Risk factors = age > 65, anemia, thrombocytopenia, high B2M, > 7 grams IgM)
  9. Paiva et al. The cellular origin and malignant transformation of Waldenström macroglobulinemia. Blood 2015;125:2370
  10. Treon et al. Somatic mutations in MYD88 and CXCR4 are determinants of clinical presentation and overall survival in Waldenström macroglobulinemia. Blood 2014;123:2791
  11. Dhodapkar et al. Long-term survival in Waldenstrom macroglobulinemia: 10-year follow-up of Southwest Oncology Group–directed intergroup trial S9003. Blood 2009;113:793(Only 20% of patients with smoldering disease not requiring initial treatment need treatment within 10 years)
  12. Kyle et al. Progression in smoldering Waldenström macroglobulinemia: long-term results. Blood 2012;119:4462(59% progressed to symptomatic disease within 5 yrs)
  13. Chng et al. Gene-expression profiling of Waldenström macroglobulinemia reveals a phenotype more similar to chronic lymphocytic leukemia than multiple myeloma. Blood 2006;108:2755
  14. Treon et al. MYD88 L265P Somatic Mutation in Waldenström’s Macroglobulinemia. NEJM 2012;367:826(>90% of patients had this NF-kB-activating mutation)
  15. Varettoni et al. Prevalence and clinical significance of the MYD88 (L265P) somatic mutation in Waldenström’s macroglobulinemia and related lymphoid neoplasms. Blood 2013;121:2522(Mutation associated with greater disease burden and higher risk of disease progression)
  16. Roos-Weil et al. Identification of 2 DNA methylation subtypes of Waldenström macroglobulinemia with plasma and memory B-cell features. Blood 2020;136:585
  17. Hivert et al. Clinical and prognostic implications of low or high level of von Willebrand factor in patients with Waldenström macroglobulinemia. Blood 2012;120:3214(High VWF levels associated with worse prognosis)
  18. Hultcrantz et al. Elevated risk of venous but not arterial thrombosis in Waldenström macroglobulinemia/lymphoplasmacytic lymphoma. J Thromb Haemost 2014;12:1816
  19. Kristinsson et al. Risk of lymphoproliferative disorders among first-degree relatives of lymphoplasmacytic lymphoma/Waldenström macroglobulinemia patients: a population-based study in Sweden. Blood 2008;112:3052(20-fold increased risk of WM, and increased risk of other lymphoproliferative disorders, in first degree relatives)
  20. Leblond et al. Results of a Randomized Trial of Chlorambucil Versus Fludarabine for Patients With Untreated Waldenström Macroglobulinemia, Marginal Zone Lymphoma, or Lymphoplasmacytic Lymphoma. J Clin Oncol 2013;31:301 (Better PFS and OS with fludarabine; more 2nd malignancies with chlorambucil)
  21. Dimopoulos et al. Primary Treatment of Waldenström Macroglobulinemia With Dexamethasone, Rituximab, and Cyclophosphamide. J Clin Oncol 2007;25:3344(7% CR, 67% PR, 67% 2-yr PFS)
  22. Buske et al. Bortezomib-Dexamethasone, Rituximab, and Cyclophosphamide as First-Line Treatment for Waldenström’s Macroglobulinemia: A Prospectively Randomized Trial of the European Consortium for Waldenström’s Macroglobulinemia. J Clin Oncol 2023;41:2607
  23. Treon et al. Long-term outcomes to fludarabine and rituximab in Waldenström macroglobulinemia. Blood 2009;113:3673 (OR rate 95%, major response rate 86%, median time to progression 51 mo)
  24. Lazlo et al. Rituximab and Subcutaneous 2-Chloro-2′-Deoxyadenosine Combination Treatment for Patients With Waldenström Macroglobulinemia: Clinical and Biologic Results of a Phase II Multicenter Study. J Clin Oncol 2010;28:2233(OR rate 90%, CR rate 24%)
  25. Treon et al. Primary Therapy of Waldenström Macroglobulinemia With Bortezomib, Dexamethasone, and Rituximab: WMCTG Clinical Trial 05-180. J Clin Oncol 2009; 27:3830 (OR rate 96%)
  26. Dimopoulos et al. Primary therapy of Waldenström macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN). Blood 2013;122:3276(OR rate 85%)
  27. Gavriatopoulou et al. BDR in newly diagnosed patients with WM: final analysis of a phase 2 study after a minimum follow-up of 6 years. Blood 2017;129:456(Median PFS 43 mo, low toxicity, good response to re-treatment with rituximab-based regimens)
  28. Treon et al. Carfilzomib, rituximab, and dexamethasone (CaRD) treatment offers a neuropathy-sparing approach for treating Waldenström’s macroglobulinemia. Blood 2014;124:503
  29. Ghobrial et al. Results of a phase 2 trial of the single-agent histone deacetylase inhibitor panobinostat in patients with relapsed/refractory Waldenström macroglobulinemia. Blood 2013;121:1296(47% had at least some improvement, no patient progressed on therapy)
  30. Treon et al. Long-term follow-up of symptomatic patients with lymphoplasmacytic lymphoma/Waldenström macroglobulinemia treated with the anti-CD52 monoclonal antibody alemtuzumab. Blood 2011;118:276(Late-onset ITP and CMV reactivation relatively common)
  31. Treon et al. Ibrutinib in Previously Treated Waldenström’s Macroglobulinemia. NEJM 2015;372:1430(90% OS, 73% “major response”; treatment well-tolerated)
  32. Treon et al. Ibrutinib Monotherapy in Symptomatic, Treatment-Naïve Patients With Waldenström Macroglobulinemia. J Clin Oncol 2018;36:2755(With editorial)
  33. Treon et al. Long-Term Follow-Up of Ibrutinib Monotherapy in Symptomatic, Previously Treated Patients With Waldenström Macroglobulinemia. J Clin Oncol 2021;39:565
  34. Dimopoulos et al. Phase 3 Trial of Ibrutinib plus Rituximab in Waldenström’s Macroglobulinemia. NEJM 2018;378:2399(82% PFS at 30 months, vs 28% with rituximab alone)
  35. Buske et al. Ibrutinib Plus Rituximab Versus Placebo Plus Rituximab for Waldenström’s Macroglobulinemia: Final Analysis From the Randomized Phase III iNNOVATE Study. J Clin Oncol 2022;40:52
  36. Castillo et al. Ibrutinib and venetoclax as primary therapy in symptomatic, treatment-naïve Waldenström macroglobulinemia. Blood 2024;143:582 (Treatment effective, but 9% of patients had ventricular arrhythmias, some fatal)
  37. Castillo et al. Ibrutinib for the treatment of Bing-Neel syndrome: a multicenter study. Blood 2019;133:299(2-year EFS 81%, 5-yr OS 86%)
  38. Trotman et al. Zanubrutinib for the treatment of patients with Waldenström macroglobulinemia: 3 years of follow-up. Blood 2020;136:2027
  39. Tam et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood 2020;136:2038(Somewhat higher response rate, less toxicity with zanubrutinib)
  40. Furman et al. Once-weekly ofatumumab in untreated or relapsed Waldenström’s macroglobulinaemia: an open-label, single-arm, phase 2 study. Lancet Haematol 2017;4:e24(59% overall response rate)
  41. Chen et al. Safety and efficacy of selinexor in relapsed or refractory multiple myeloma and Waldenstrom macroglobulinemia. Blood 2018;131:855
  42. Leleu et al. Increased Incidence of Transformation and Myelodysplasia/Acute Leukemia in Patients With Waldenström Macroglobulinemia Treated With Nucleoside Analogs. J Clin Oncol 2009;27:250
  43. Treon et al. Phase 1 study of ibrutinib and the CXCR4 antagonist ulocuplumab in CXCR4-mutated Waldenström macroglobulinemia. Blood 2021;138:1535
  44. Kyle et al.  Long-term follow-up of IgM monoclonal gammopathy of undetermined significance. Blood 2003;102:3759
  45. Elessa et al. Inflammatory Waldenström’s macroglobulinaemia: A French monocentric retrospective study of 67 patients. Br J Haem 2022;197;728
  46. Debureaux et al. Inflammatory Waldenström macroglobulinemia is associated with clonal hematopoiesis: a multicentric cohort. Blood 2025;145:450
  47. Vos et al. Renal disease related to Waldenström macroglobulinaemia: incidence, pathology and clinical outcomes. Br J Haem 2016;175:623
  48. Rowczenio et al. Molecular genetic investigation, clinical features, and response to treatment in 21 patients with Schnitzler syndrome. Blood 2018;131:974(Treatment with IL-1 antagonists such as anakinra produces “dramatic” benefit)

Amyloidosis and related conditions – general

  1. D’Sousa A. Amyloid consults do not have to be vexing. Hematology Am Soc Hematol Educ Program (2023): 407
  2. Falk et al. The systemic amyloidoses. NEJM 1997;337:898
  3. Sanchorawala V. Systemic Light Chain Amyloidosis. NEJM 2024:390:2295
  4. Leung et al. How I treat amyloidosis: the importance of accurate diagnosis and amyloid typing. Blood 2012;120:3206
  5. Wechalekar et al. AL amyloidosis associated with IgM paraproteinemia: clinical profile and treatment outcome. Blood 2008;112:4009
  6. Merlini and Bellotti.   Molecular mechanisms of amyloidosis.  NEJM 2003;349:583
  7. Kourelis et al. Clarifying immunoglobulin gene usage in systemic and localized immunoglobulin light-chain amyloidosis by mass spectrometry. Blood 2017;129:299 (Organ tropism is partially explained by light chain gene usage)
  8. Kumar et al. Revised Prognostic Staging System for Light Chain Amyloidosis Incorporating Cardiac Biomarkers and Serum Free Light Chain Measurements. J Clin Oncol 2012;30:989
  9. Lilleness et al. Development and validation of a survival staging system incorporating BNP in patients with light chain amyloidosis. Blood 2019;133:215
  10. Vrana et al. Classification of amyloidosis by laser microdissection and mass spectrometry–based proteomic analysis in clinical biopsy specimens. Blood 2009;114:4957
  11. Brambilla et al. Reliable typing of systemic amyloidoses through proteomic analysis of subcutaneous adipose tissue. Blood 2012;119:1844
  12. Schönland et al. Immunohistochemistry in the classification of systemic forms of amyloidosis: a systematic investigation of 117 patients. Blood 2012;119:488
  13. Paiva et al. The clinical utility and prognostic value of multiparameter flow cytometry immunophenotyping in light-chain amyloidosis. Blood 2011;117:3613 (More monoclonal plasma cells in marrow associated with worse prognosis)
  14. Kourelis et al. Coexistent Multiple Myeloma or Increased Bone Marrow Plasma Cells Define Equally High-Risk Populations in Patients With Immunoglobulin Light Chain Amyloidosis. J Clin Oncol 2013;31:4319(>10% marrow plasma cells = high risk similar to that with frank myeloma)
  15. Milani et al. Patients with light-chain amyloidosis and low free light-chain burden have distinct clinical features and outcome. Blood 2017;130:625(Less cardiac involvement, better survival)
  16. Dittrich et al. AL amyloidosis patients with low amyloidogenic free light chain levels at first diagnosis have an excellent prognosis. Blood 2017;130:632(Low light chain defined as less than 50 mg/L difference between involved and uninvolved light chain levels)
  17. Kourelis et al. Presentation and Outcomes of Localized Immunoglobulin Light Chain Amyloidosis. The Mayo Clinic Experience. Mayo Clin Proc 2017;92:908(Urothelial tissue and larynx most common sites; local recurrence common, systemic progression did not occur, outcomes generally excellent)
  18. Benson et al. Hereditary systemic immunoglobulin light-chain amyloidosis. Blood 2015;125:3281(Amyloidogenic mutation in constant region of Ig kappa light chain)
  19. Kumar et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood 2010;116:5126(Light chain type impacts pattern of organ involvement; free light chain burden correlates with survival)
  20. Basset et al. Nonlymphoplasmacytic lymphomas associated with light-chain amyloidosis. Blood 2020;135:293(2% of patients with systemic AL amyloid and 5% of those with localized amyloid had non-lymphoplasmacytic lymphomas)
  21. Hammarström P. The bloody path of amyloids and prions. J Thromb Haemost 2007;5:1136(Hemostatic abnormalities in amyloidosis)

Treatment of AL amyloidosis

  1. Gertz MA. Immunoglobulin light chain amyloidosis: 2024 update on diagnosis, prognosis, and treatment. Am J Hematol 2024;99:324
  2. Palladini and Merlini. How I treat AL amyloidosis. Blood 2022;139:2918
  3. Palladini and Merlini. What is new in diagnosis and management of light chain amyloidosis? Blood 2016;128:159
  4. Bomsztyk et al. Complete responses in AL amyloidosis are unequal: the impact of free light chain mass spectrometry in AL amyloidosis. Blood 2024;143:1259 (Persistence of serum light chain by mass spec predicts relapse)
  5. Muchtar et al. Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death. Blood 2017;129:2111
  6. Wechalekar et al. Guidelines on the management of AL amyloidosis. Br J Haematol 2015;168:186
  7. Dispenzieri et al. Treatment of Immunoglobulin Light Chain Amyloidosis. Mayo Stratification of Myeloma and Risk-Adapted Therapy (mSMART) Consensus Statement. Mayo Clin Proc 2015;90:1054
  8. Weiss et al. Beyond the plasma cell: emerging therapies for immunoglobulin light chain amyloidosis. Blood 2016;127:2275
  9. Gertz et al. Birtamimab plus standard of care in light-chain amyloidosis: the phase 3 randomized placebo-controlled VITAL trial. Blood 2023;142:1208 (MoAb to neutralize light chain aggregates, enhance clearance of amyloid.  Possible survival benefit in highest risk patients)
  10. Palladini et al. New Criteria for Response to Treatment in Immunoglobulin Light Chain Amyloidosis Based on Free Light Chain Measurement and Cardiac Biomarkers: Impact on Survival Outcomes. J Clin Oncol 2012;30:4541(“Changes in FLC and NT-proBNP predicted survival as early as 3 mo”)
  11. Pinney et al. Outcome in renal AL amyloidosis after chemotherapy. J Clin Oncol 2011;29:674(FLC measurements correlate with clinical outcome)
  12. Palladini et al. A staging system for renal outcome and early markers of renal response to chemotherapy in AL amyloidosis. Blood 2014;124:2325
  13. Kastritis et al. Bortezomib, Melphalan, and Dexamethasone for Light-Chain Amyloidosis. J Clin Oncol 2020;38:3252 (Superior outcomes with BMDex vs MDex)
  14. Reece et al. Weekly and twice-weekly bortezomib in patients with systemic AL amyloidosis: results of a phase 1 dose-escalation study. Blood 2009;114:1489(50% OR rate, 20% CR; acceptable toxicity with both regimens)
  15. Kastritis et al. Bortezomib With or Without Dexamethasone in Primary Systemic (Light Chain) Amyloidosis. J Clin Oncol 2010;28:1031
  16. Reece et al. Long-term follow-up from a phase 1/2 study of single-agent bortezomib in relapsed systemic AL amyloidosis. Blood 2014;124:2498(Durable hematologic responses and “promising OS”; once weekly administration less toxic, equally effective)
  17. Manwani et al. A prospective observational study of 915 patients with systemic AL amyloidosis treated with upfront bortezomib. Blood 2019;134:2271
  18. Venner et al. Cyclophosphamide, bortezomib, and dexamethasone therapy in AL amyloidosis is associated with high clonal response rates and prolonged progression-free survival. Blood 2012;119:4387(66% 2-yr PFS, 98% OS in previously untreated pts)
  19. Mikhael et al. Cyclophosphamide-bortezomib-dexamethasone (CyBorD) produces rapid and complete hematologic response in patients with AL amyloidosis. Blood 2012;119:4391
  20. Dispenzieri et al. The activity of lenalidomide with or without dexamethasone in patients with primary systemic amyloidosis. Blood 2007;109:465 (Improved response rates when dexamethasone added)
  21. Sanchorawala et al. Lenalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 2 trial. Blood 2007; 109:492 (67% OR)
  22. Moreau et al. Lenalidomide in combination with melphalan and dexamethasone in patients with newly diagnosed AL amyloidosis: a multicenter phase 1/2 dose-escalation study Blood 2010;116:4777
  23. Kumar et al. Lenalidomide, cyclophosphamide, and dexamethasone (CRd) for light-chain amyloidosis: long-term results from a phase 2 trial. Blood 2012;119:4860(PR or better in 60%, median OS 38 mo)
  24. Kastritis et al. A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis. Blood 2012;119:5384
  25. Dispenzieri et al. Activity of pomalidomide in patients with immunoglobulin light-chain amyloidosis. Blood 2012;119:5397
  26. Sanchorawala et al. Pomalidomide and dexamethasone in the treatment of AL amyloidosis: results of a phase 1 and 2 trial. Blood 2016;128:1059
  27. Palladini et al. A phase 2 trial of pomalidomide and dexamethasone rescue treatment in patients with AL amyloidosis. Blood 2017;129:2120
  28. Reece et al. Efficacy and safety of once-weekly and twice-weekly bortezomib in patients with relapsed systemic AL amyloidosis: results of a phase 1/2 study. Blood 2011;118:865
  29. Wechalekar et al. Safety and efficacy of risk-adapted cyclophosphamide, thalidomide, and dexamethasone in systemic AL amyloidosis. Blood 2007;109:457(74% OR)
  30. Palladini et al. A European collaborative study of cyclophosphamide, bortezomib, and dexamethasone in upfront treatment of systemic AL amyloidosis. Blood 2015;126:612(60% OR)
  31. Kaufman et al. Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis. Blood 2017;130:900
  32. Kimmich et al. Daratumumab for systemic AL amyloidosis: prognostic factors and adverse outcome with nephrotic-range albuminuria. Blood 2020;135:1517
  33. Sanchorawala et al. Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study. Blood 2020;135:1541
  34. Palladini et al. Daratumumab plus CyBorD for patients with newly diagnosed AL amyloidosis: safety run-in results of ANDROMEDA. Blood 2020;136:71
  35. Kastritis et al. Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis. NEJM 2021;385:46(ANDROMEDA trial; Dara+CyBorD superior to CyBorD alone)
  36. Richards et al. Therapeutic Clearance of Amyloid by Antibodies to Serum Amyloid P Component. NEJM 2015;373:1106
  37. Wechalekar and Sanchorawala. Daratumumab in AL amyloidosis. Blood 2022;140:2317
  38. Sher et al. First report of safety and efficacy of daratumumab in 2 cases of advanced immunoglobulin light chain amyloidosis (letter). Blood 2016;128:1987
  39. Sanchorawala et al. A phase 1/2 study of the oral proteasome inhibitor ixazomib in relapsed or refractory AL amyloidosis. Blood 2017;130:597(Over 50% of patients responded, treatment well-tolerated)
  40. Palladini et al. Presentation and outcome with second-line treatment in AL amyloidosis previously sensitive to nontransplant therapies. Blood 2018;131:525
  41. Manwani et al. Treatment of IgM-associated immunoglobulin light-chain amyloidosis with rituximab-bendamustine. Blood 2018;132:761
  42. Milani et al.Treatment of AL amyloidosis with bendamustine: a study of 122 patients. Blood 2018;132:1988
  43. Sachchithanantham. European Collaborative Study Defining Clinical Profile Outcomes and Novel Prognostic Criteria in Monoclonal Immunoglobulin M–Related Light Chain Amyloidosis. J Clin Oncol. 2016;34:2037
  44. Edwards et al. Phase 1a/b study of monoclonal antibody CAEL-101 (11-1F4) in patients with AL amyloidosis. Blood 2021;138:2632(Anti-light chain Ab reverses organ toxicity)
  45. Forgeard et al. Teclistamab in relapsed or refractory AL amyloidosis: a multinational retrospective case series. Blood 2024;143:734

Cardiac amyloidosis

  1. Bloom and Gorevic.  Cardiac Amyloidosis.  Ann Intern Med 2023;176:ITC33
  2. Diomede et al. A Caenorhabditis elegans–based assay recognizes immunoglobulin light chains causing heart amyloidosis. Blood 2014;123:3543
  3. Dietrich et al. Treatment with intravenous melphalan and dexamethasone is not able to overcome the poor prognosis of patients with newly diagnosed systemic light chain amyloidosis and severe cardiac involvement. Blood 2010;116:522
  4. Sher et al. First report of safety and efficacy of daratumumab in 2 cases of advanced immunoglobulin light chain amyloidosis (letter). Blood 2016;128:1987
  5. Feng et al. Intracardiac thrombosis and embolism in patients with cardiac amyloidosis. Circulation 2007;116:2420
  6. Lee et al. Cardiac amyloidosis without increased left ventricular wall thickness. Mayo Clin Proc 2014;89:781(One third of patients with AL cardiac amyloid did not have increased wall thickness)
  7. Palladini et al. Circulating amyloidogenic free light chains and serum N-terminal natriuretic peptide type B decrease simultaneously in association with improvement of survival in AL. Blood 2006;107:3854   (Decreased circulating free light chains after treatment associated with better cardiac function even though echocardiogram showed no change in amount of amyloid)
  8. Kristen et al. Assessment of disease severity and outcome in patients with systemic light-chain amyloidosis by the high-sensitivity troponin T assay. Blood 2010;116:2455
  9. Fontana et al. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. Circulation 2015;132:1570
  10. Wechalekar et al. A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis. Blood 2013;121:3420
  11. Gillmore et al. Nonbiopsy diagnosis of cardiac transthyretin amyloidosis. Circulation 2016;133:2404(Using bone scintigraphy)
  12. Parcha et al. Association of Transthyretin Val122Ile Variant With Incident Heart Failure Among Black Individuals. JAMA 2022;327:1368 (3.1% of population are carriers; carriers  had 2-fold higher risk of heart failure)
  13. Connors et al. Heart Failure Resulting From Age-Related Cardiac Amyloid Disease Associated With Wild-Type Transthyretin. A Prospective, Observational Cohort Study. Circulation 2016;133:282(“Senile” cardiac amyloid; may affect patients in their 60s and up; 10% had incidental finding of monoclonal gammopathy)
  14. Tana et al. Thromboembolic and bleeding risk in cardiac amyloidosis. J Thromb Haemost 2024:22:2381

Non-AL amyloidosis

  1. Lachmann et al. Natural History and Outcome in Systemic AA Amyloidosis. NEJM 2007;356:2361
  2. Stangou et al. Hereditary fibrinogen A α-chain amyloidosis: phenotypic characterization of a systemic disease and the role of liver transplantation. Blood 2010;115:2998
  3. Adams et al. Hereditary transthyretin amyloidosis in the era of RNA interference, antisense oligonucleotide, and CRISPR-Cas9 treatments. Blood 2023;142:1600
  4. Ando et al. Guideline of transthyretin-related hereditary amyloidosis for clinicians. Orphanet J Rare Dis 2013;8:31
  5. Lane et al. Natural History, Quality of Life, and Outcome in Cardiac Transthyretin Amyloidosis. Circulation 2019;140:16
  6. Coelho et al. Safety and Efficacy of RNAi Therapy for Transthyretin Amyloidosis. NEJM 2013;369:819
  7. Berk et al. Repurposing Diflunisal for Familial Amyloid Polyneuropathy. A Randomized Clinical Trial. JAMA 2013;310:2658
  8. Mereuta et al. Leukocyte cell-derived chemotaxin 2 (LECT2)–associated amyloidosis is a frequent cause of hepatic amyloidosis in the United States. Blood 2014;123:1479
  9. Quarta et al. The Amyloidogenic V122I Transthyretin Variant in Elderly Black Americans. NEJM 2015;372:21(No increase in mortality but increased risk of heart failure in carriers of this common TTR variant)
  10. Geller et al. Prevalence of Monoclonal Gammopathy in Wild-Type Transthyretin Amyloidosis. Mayo Clin Proc 2017;92:1800(23% of patients with “senile” amyloidosis have monoclonal gammopathy)
  11. Adams et al. Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis. NEJM 2018;379:11(With editorial)
  12. Maurer et al. Patisiran Treatment in Patients with Transthyretin Cardiac Amyloidosis. NEJM 2023;389:1553 (With editorial)
  13. Benson et al. Inotersen Treatment for Patients with Hereditary Transthyretin Amyloidosis. NEJM 2018;379:22(Drug caused neurologic improvement but caused thrombocytopenia and kidney injury; with editorial)
  14. Maurer et al. Tafamidis Treatment for Patients with Transthyretin Amyloid Cardiomyopathy. NEJM 2018;379:1007(with editorial)
  15. Gillmore et al. CRISPR-Cas9 In Vivo Gene Editing for Transthyretin Amyloidosis. NEJM 2021;385:493(with editorial)
  16. Solomon et al. Effects of Patisiran, an RNA Interference Therapeutic, on Cardiac Parameters in Patients With Hereditary Transthyretin-Mediated Amyloidosis. Circulation 2019;139:431
  17. Fontana et al. Vutrisiran in Patients with Transthyretin Amyloidosis with Cardiomyopathy. NEJM 2025;392:33 (With editorial)
  18. Gillmore et al. Efficacy and Safety of Acoramidis in Transthyretin Amyloid Cardiomyopathy. NEJM 2024;390:132
  19. Garcia-Pavia et al. Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid. NEJM 2023;389:239

Amyloidosis: Stem Cell Transplantation

Complications of monoclonal gammopathies

  1. Castillo et al. The evaluation and management of monoclonal gammopathy of renal significance and monoclonal gammopathy of neurological significance. Am J Hematol 2021;96:846
  2. Merlini and Stone. Dangerous small B-cell clones. Blood 2006;108:2520(Review of monoclonal gammopathy-related disorders)
  3. Fermand et al. Monoclonal gammopathy of clinical significance: a novel concept with therapeutic implications. Blood 2018;132:1478(Reviews various conditions associated with monoclonal gammopathy that cause organ damage or other disease)
  4. Ropper and Gorson. Neuropathies associated with paraproteinemia. NEJM 1998;338:1601
  5. Dispenzieri A. POEMS syndrome: Update on diagnosis, risk-stratification, and management. Am J Hematol 2023;98:1934
  6. Dao et al.Bone marrow histopathology in POEMS syndrome: a distinctive combination of plasma cell, lymphoid, and myeloid findings in 87 patients. Blood 2011;117:6438
  7. D’Souza et al. The utility of plasma vascular endothelial growth factor levels in the diagnosis and follow-up of patients with POEMS syndrome. Blood 2011;118:4663
  8. Allam et al. Pulmonary manifestations in patients with POEMS syndrome. A retrospective review of 137 patients. Chest 2008;133:969
  9. Badros et al. Bevacizumab therapy for POEMS syndrome. Blood 2005;106:1135
  10. Li et al. Combination of melphalan and dexamethasone for patients with newly diagnosed POEMS syndrome. Blood 2011;117:6445(81% response rate)
  11. Humeniuk et al. Outcomes of patients with POEMS syndrome treated initially with radiation. Blood 2013;122(“Durable, meaningful responses” in selected pts)
  12. Gertz MA. Acute hyperviscosity: syndromes and mamagement. Blood 2018;132:1379
  13. Stone and Bogen. Evidence-based focused review of management of hyperviscosity syndrome. Blood 2012;119:2205
  14. Corcos et al. B-cell receptors and heavy chain diseases: guilty by association? Blood 2011;117:6991
  15. Giannelli et al.  Effect of antiviral treatment in patients with chronic HCV infection and t(14;18) translocation.  Blood 2003;102:1196
  16. Druey and Greipp. Narrative review: the systemic capillary leak syndrome. Ann Intern Med 2010; 153:90
  17. Gousseff et al. The Systemic Capillary Leak Syndrome: A Case Series of 28 Patients From a European Registry. Ann Intern Med 2011;154:464
  18. Xie et al. Vascular endothelial hyperpermeability induces the clinical symptoms of Clarkson disease (the systemic capillary leak syndrome). Blood 2012;119:4321(Non-immunoglobulin humoral factors contribute to transient endothelial dysfunction)
  19. Szalat et al. Pathogenesis and treatment of xanthomatosis associated with monoclonal gammopathy. Blood 2011;118:3777
  20. Sykes et al. The TEMPI Syndrome — A Novel Multisystem Disease. NEJM 2011;365:475 (Erythrocytosis, elevated EPO, telangiectasias, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting)
  21. Sykes et al. The TEMPI syndrome. Blood 2020;135:1199
  22. Sykes and Schroyens. Complete Responses in the TEMPI Syndrome after Treatment with Daratumumab. NEJM 2018;378:2240
  23. Sykes and Schroyens. Teclistamab as Successful Treatment of Relapsed TEMPI Syndrome. NEJM 2024;391:2173  (Same patient as above?)
  24. Camus et al. Proteomic evidence of specific IGKV1-8 association with cystic lung light chain deposition disease. Blood 2019;133:2741
  25. Mahévas et al. Plasma cell–directed therapies in monoclonal gammopathy–associated scleromyxedema. Blood 2020;135:1101
  26. Le Cann et al. CANOMAD: a neurological monoclonal gammopathy of clinical significance that benefits from B-cell–targeted therapies. Blood 2020;136:2428(IgM gammopathy, chronic ataxic neuropathy, opthalmoplegia, cold agglutinins and disialosyl antibodies)
  27. Kanack et al. Monoclonal gammopathy of thrombotic/thrombocytopenic significance. Blood 2023;141:1772 (HIT-like disorder, monoclonal Ab reacting with heparin-PF4 complex)
  28. Wang et al. VITT-like Monoclonal Gammopathy of Thrombotic Significance. NEJM 2025;392:995
  29. Salmasi et al. Myeloma Therapy for Monoclonal Gammopathy of Thrombotic Significance. NEJM 2024;391:570

Monoclonal gammopathy of renal significance

  1. Leung et al. The evaluation of monoclonal gammopathy of renal significance: a consensus report of the International Kidney and Monoclonal Gammopathy Research Group. Nat Rev Nephrol 2019;15:45
  2. Leung et al. Monoclonal gammopathy of renal significance. NEJM 2021;384:1931
  3. Sayed et al. Natural history and outcome of light chain deposition disease. Blood 2015;126:2805(Aggressive chemotherapy and auto-SCT appears to benefit many patients)
  4. Leung et al. Monoclonal gammopathy of renal significance: when MGUS is no longer undetermined or insignificant. Blood 2012;120:4292
  5. Sethi and Rajkumar. Monoclonal gammopathy-associated proliferative glomerulonephritis. Mayo Clin Proc 2013;88:1284
  6. Bhutani et al. Hematologic Characteristics of Proliferative Glomerulonephritides With Nonorganized Monoclonal Immunoglobulin Deposits. Mayo Clin Proc 2015;90:587
  7. Chauvet et al. Treatment of B-cell disorder improves renal outcome of patients with monoclonal gammopathy–associated C3 glomerulopathy. Blood 2017;129:1437(With editorial)
  8. Ma et al. Acquired Fanconi syndrome is an indolent disorder in the absence of overt multiple myeloma. Blood 2004;104:40
  9. Joly et al. Randall-type monoclonal immunoglobulin deposition disease: novel insights from a nationwide cohort study. Blood 2019;133:576

Cryoglobulinemia

  1. Cacoub et al. Cryoglobulinemia — One Name for Two Diseases. NEJM 2024;391:1426
  2. Muchtar et al. How I treat cryoglobulinemia. Blood 2017;129:289
  3. Morra E. Cryoglobulinemia. Hematology 2005:368-372
  4. Beddhu et al. The clinical and morphological spectrum of renal cryoglobulinemia. Medicine 2002;81:398
  5. Terrier et al. Management of noninfectious mixed cryoglobulinemia vasculitis; data from 242 cases included in the CryoVas survey. Blood 2012;119:5996(Rituximab plus corticosteroids most effective therapy)
  6. Saadoun et al. Increased Risks of Lymphoma and Death Among Patients With Non–Hepatitis C Virus–Related Mixed Cryoglobulinemia. Arch Intern Med 2006;166:2101
  7. Monti et al. Incidence and Characteristics of Non-Hodgkin Lymphomas in a Multicenter Case File of Patients With Hepatitis C Virus–Related Symptomatic Mixed Cryoglobulinemias. Arch Intern Med 2005; 165:101
  8. Zignego et al. Prevalence of bcl-2 rearrangement in patients with hepatitis C virus-related mixed cryoglobulinemia with or without B-cell lymphoma. Ann Intern Med 2002;137:571
  9. Saadoun D. Restoration of peripheral immune homeostasis after rituximab in mixed cryoglobulinemia vasculitis. Blood 2008;111:5334
  10. Saadoun et al. Rituximab plus Peg-interferon-/ribavirin compared with Peg-interferon-/ribavirin in hepatitis C–related mixed cryoglobulinemia. Blood 2010;116: 326
  11. Petrarca et al. Safety and efficacy of rituximab in patients with hepatitis C virus–related mixed cryoglobulinemia and severe liver disease. Blood 2010;116:335
  12. Dammacco et al. Pegylated interferon-, ribavirin, and rituximab combined therapy of hepatitis C virus–related mixed cryoglobulinemia: a long-term study. Blood 2010;116:343
  13. Saadoun et al. Regulatory T-Cell Responses to Low-Dose Interleukin-2 in HCV-Induced Vasculitis. NEJM 2011;365:2067
  14. Dammacco and Sansonno. Therapy for hepatitis C virus-related cryoglobulinemic vasculitits. NEJM 2013;369:1035

Polyclonal hypergammaglobulinemia

  1. Zhao et al. Polyclonal hypergammaglobulinaemia: assessment, clinical interpretation, and management. Lancet Haematol 2021;8:e365