University of Wisconsin Hematology

Pharmacology of antineoplastic agents (drugs & biologicals)

  1. Dawson et al. Targeting epigenetic readers in cancer. NEJM 2012;367:647
  2. Mohammad et al. Targeting epigenetic modifications in cancer therapy: erasing the roadmap to cancer. Nat Med 2019;25:403
  3. McLorman et al. Applying Synthetic Lethality for the Selective Targeting of Cancer. NEJM 2014;371:1725
  4. Hijiya et al. Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia. Blood 2006;108:3997(Concludes that drug doses should be calculated on basis of actual rather than ideal body surface area)
  5. Bolufer et al. Profile of polymorphisms of drug-metabolising enzymes and the risk of therapy-related leukaemia. Br J Haematol 2007;136:590
  6. Hartford et al. Population-specific genetic variants important in susceptibility to cytarabine arabinoside cytotoxicity. Blood 2009;113:2145
  7. Reed and Pellecchia. Apoptosis-based therapies for hematologic malignancies. Blood 2005;106:408
  8. Saven and Piro. 2-Chlorodeoxyadenosine: a newer purine analog active in the treatment of indolent lymphoid malignancies. Ann Intern Med 1994;120:784
  9. Sigal et al. Beyond hairy cell: the activity of cladribine in other hematologic malignancies. Blood 2010;116:2884
  10. Moreau et al. Proteasome inhibitors in multiple myeloma: 10 years later. Blood 2012;120:947
  11. Rhen and Cidlowski.  Antiinflammatory action of glucocorticoids – new mechanisms for old drugs. NEJM 2005;353:1711
  12. Boumpas et al. Glucocorticoid therapy for immune-mediated diseases: basic and clinical correlates. Ann Intern Med 1993;119:1198
  13. Schlaghecke et al. The effect of long-term glucocorticoid therapy on pituitary-adrenal responses to exogenous corticotropin-releasing hormone. NEJM 1992; 326:226
  14. Weinstein RS. Glucocorticoid-induced bone disease. NEJM 2011;365:62
  15. Aldoss and Douerl. How I treat the toxicities of pegasparaginase in adults with acute lymphoblastic leukemia. Blood 2020;135:987
  16. Gupta et al. Glucarpidase for treatment of high-dose methotrexate toxicity. Blood 2025;145:1858
  17. Knight et al; Rajkumar and Blood.  Lenalidomide and venous thrombosis in multiple myeloma [letters].  NEJM 2006;354:2079
  18. Lacy and McCurdy. Pomalidomide. Blood 2013;122:2305
  19. Krönke et al. Lenalidomide Causes Selective Degradation of IKZF1 and IKZF3 in Multiple Myeloma Cells. Science 2014;343:301(see also editorial “How thalidomide works against cancer”)
  20. Lu et al. The myeloma drug lenalidomide promotes the cereblon-dependent destruction of Ikaros proteins. Science 2014;343:305 (see also editorial “How thalidomide works against cancer”)
  21. Fink and Ebert. The novel mechanism of lenalidomide activity. Blood 2015;126:2366
  22. Eichner et al. Immunomodulatory drugs disrupt the cereblon–CD147–MCT1 axis to exert antitumor activity and teratogenicity. Nat Med 2016;22:735
  23. Kater et al. How does lenalidomide target the chronic lymphocytic leukemia microenvironment? Blood 2014;124:2184
  24. Kritharis et al. Lenalidomide in non-Hodgkin lymphoma: biological perspectives and therapeutic opportunities. Blood 2015;125:2471
  25. Sperling et al. Lenalidomide promotes the development of TP53-mutated therapy-related myeloid neoplasms. Blood 2022;140:1753
  26. Saleem et al. Second primary malignancies in patients with haematological cancers treated with lenalidomide: a systematic review and meta-analysis. Lancet Haematol 2022;9:e906 (2nd malignancies “exclusively in patients with multiple myeloma”)
  27. Argyriou et al. Bortezomib-induced peripheral neuropathy in multiple myeloma: a comprehensive review of the literature. Blood 2008; 112:1593
  28. Cornell et al. Prospective Study of Cardiac Events During Proteasome Inhibitor Therapy for Relapsed Multiple Myeloma. J Clin Oncol 2019;37:1946
  29. Lancet and Karp. Farnesyltransferase inhibitors in hematologic malignancies: new horizons in therapy.  Blood 2003;102:3880.
  30. Cunha and Pietras. ALK1 as an emerging target for antiangiogenic therapy of cancer. Blood 2011; 117:6999
  31. Cardinale et al. Early Detection of Anthracycline Cardiotoxicity and Improvement With Heart Failure Therapy. Circulation 2015;131:1981(With editorial)
  32. Garcia-Pavia et al. Genetic Variants Associated With Cancer Therapy–Induced Cardiomyopathy. Circulation 2019;140:31 (Titin-truncating variants increase cardiomyopathy risk)
  33. Vano-Galvan and Jaen. Extravasation of epirubicin. NEJM 2009;360:2117
  34. Berman et al. Altered Bone and Mineral Metabolism in Patients Receiving Imatinib Mesylate. NEJM 2006;354:2006
  35. Veltmaat and Cortes. Arterio-occlusive events among patients with chronic myeloid leukemia on tyrosine kinase inhibitors. Blood 2024;143:858
  36. Wadleigh et al. After chronic myelogenous leukemia: tyrosine kinase inhibitors in other hematologic malignancies. Blood 2005;105:22
  37. Douer et al. Pharmacodynamics and safety of intravenous pegaspargase during remission induction in adults aged 55 years or younger with newly diagnosed acute lymphoblastic leukemia. Blood 2007;109:2744
  38. Rosenbeck ande Kiel. Palmar-plantar rash with cytarabine therapy. NEJM 2011;364:e5
  39. Kiladjian et al. The renaissance of interferon therapy for the treatment of myeloid malignancies. Blood 2011;117:4706
  40. Amos et al. Autoimmunity associated with immunotherapy of cancer. Blood 2011;118:499
  41. Roberts et al. BCL2 and MCL1 inhibitors for hematologic malignancies. Blood 2021;138:1120
  42. Stephens and Byrd. Resistance to Bruton tyrosine kinase inhibitors: the Achilles heel of their success story in lymphoid malignancies. Blood 2021;138:1099
  43. Woyach et al. Resistance mechanisms for the Bruton’s tyrosine kinase inhibitor ibruitnib. NEJM 2014;370:2286
  44. Abdel-Qadir et al. Cardiovascular Risk Associated With Ibrutinib Use in Chronic Lymphocytic Leukemia: A Population-Based Cohort Study. J Clin Oncol 2021;39:3453
  45. Barr et al. Impact of ibrutinib dose adherence on therapeutic efficacy in patients with previously treated CLL/SLL. Blood 2017;129:2612(Poor adherence or stopping drug > 1 week associated with adverse events)
  46. Levade et al. Ibrutinib treatment affects collagen and von Willebrand factor-dependent platelet functions. Blood 2014;124:3991(Bleeding occurs in up to 50% of treated pts. Platelet transfusion helpful)
  47. Shatzel et al. Ibrutinib-associated bleeding: pathogenesis, management and risk reduction strategies. J Thromb Haemost 2017;15:835(Fatal bleeding rare; post-procedure bleeding common)
  48. Busygina et al. Oral Bruton tyrosine kinase inhibitors selectively block atherosclerotic plaque–triggered thrombus formation in humans. Blood 2018;131:2605 (Low dose Btk inhibitors block platelet thrombus formation on atherosclerotic plaque, but spare normal hemostasis)
  49. Dickerson et al. Hypertension and incident cardiovascular events following ibrutinib initiation. Blood 2019;134:1919 (72% incidence of new HTN in lymphoma pts, 2x higher risk of other cardiac events)
  50. Bhat et al. Ventricular arrhythmias and sudden death events following acalabrutinib initiation. Blood 2022;140:2142
  51. Ghez et al. Early-onset invasive aspergillosis and other fungal infections in patients treated with ibrutinib. Blood 2018;131:1955
  52. Thompson et al. Atrial fibrillation in CLL patients treated with ibrutinib. An international retrospective study. Br J Haem 2016;175:462
  53. Thompson and Tam. Pirtobrutinib: a new hope for patients with BTK inhibitor–refractory lymphoproliferative disorders. Blood 2023;141L3137
  54. Gomez et al. Preclinical characterization of pirtobrutinib, a highly selective, noncovalent (reversible) BTK inhibitor.  Blood 2023;142:62
  55. Spencer et al. The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma. Blood 2014;124:2190 (Drug has activity against a variety of heme malignancies)
  56. Yoda et al. Mutations in G protein β subunits promote transformation and kinase inhibitor resistance. Nat Med 2015;21:71
  57. Roboz et al. Prevalence, Management, and Clinical Consequences of QT Interval Prolongation During Treatment With Arsenic Trioxide. J Clin Oncol 2014;32:3723(QT prolongation common, clinically significant events rare)
  58. Cheah and Fowler. Idelalisib in the management of lymphoma. Blood 2016;128:331
  59. Xu  et al. Targeting B-cell receptor and PI3K signaling in diffuse large B-cell lymphoma. Blood 2021;138:1110
  60. Perl AE. Availability of FLT3 inhibitors: how do we use them? Blood 2019;134:741
  61. Valentin et al. The rise of apoptosis: targeting apoptosis in hematologic malignancies. Blood 2018;132:1248
  62. Casan and Seymour. Degraders upgraded: the rise of PROTACs in hematological malignancies. Blood 2024;143:1218
  63. Davids MS. Targeting BCL-2 in B-cell lymphomas. Blood 2017;130:1081
  64. Machlus et al. Selinexor-induced thrombocytopenia results from inhibition of thrombopoietin signaling in early megakaryopoiesis. Blood 2017;130:1132
  65. Curtis et al. Patients treated with oxaliplatin are at risk for thrombocytopenia caused by multiple drug-dependent antibodies. Blood 2018;131:1486
  66. Tullemans et al. Acquired platelet antagonism: off‐target antiplatelet effects of malignancy treatment with tyrosine kinase inhibitors. J Thromb Haemost 2018;16:1686
  67. Nalluri et al. Risk of Venous Thromboembolism With the Angiogenesis Inhibitor Bevacizumab in Cancer Patients. A Meta-analysis. JAMA 2008;300:19
  68. Watson and Al-Samkari. Thrombotic and bleeding risk of angiogenesis inhibitors in patients with and without malignancy. J Thromb Haemost 2021;19:1852
  69. Olson et al. Cyclin-Dependent Kinase Inhibitor–Associated Thromboembolism. JAMA Oncol 2019;5:141
  70. Watson et al. Cyclin-dependent kinase 4/6 inhibitor-associated thromboembolism: a critical evaluation of the current evidence. J Thromb Haemost 2023;21:758 (Palcociclib, ribociclib, and abemaciclib)
  71. Russo et al. Adaptive mutability of colorectal cancers in response to targeted therapies. Science 2019;366:1473 (Targeted therapies enhance cancer cell mutation rates and promote therapy resistance)
  72. Blomberg et al. Clonal hematopoiesis, myeloid disorders and BAX-mutated myelopoiesis in patients receiving venetoclax for CLL. Blood 2022;139:1198
  73. Geocadin R. Posterior Reversible Encephalopathy Syndrome. NEJM 2023;388:2171

Monoclonal antibodies, immunoconjugates and immunotherapy

  1. Palanca-Wessels and Press. Advances in the treatment of hematologic malignancies using immunoconjugates. Blood 2014;123:2293
  2. Beers et al. Influence of immunoglobulin isotype on therapeutic antibody function. Blood 2016;127:1097
  3. Maloney D. Anti-CD20 antibody therapy for B-cell lymphomas. NEJM 2012;366:2008
  4. Alduaij and Illidge. The future of anti-CD20 monoclonal antibodies: are we making progress? Blood 2011;117:2993
  5. Cartron et al. Therapeutic activity of humanized anti-CD20 monoclonal antibody and polymorphism in IgG FcRIIIa gene. Blood 2002;99:754
  6. Thaunat et al. Am”B”valent: anti-CD20 antibodies unravel the dual role of B cells in immunopathogenesis. Blood 2010;116:515
  7. Friedberg J. Unique Toxicities and Resistance Mechanisms Associated with Monoclonal Antibody Therapy.  Hematology 2005:329-334
  8. Müller et al. The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood 2012;119:3276(Men clear rituximab faster than women)
  9. Nazi et al. The effect of rituximab on vaccine responses in patients with immune thrombocytopenia. Blood 2013;122:1946(Ab response to vaccination decreased for at least 6 mo after rituximab treatment)
  10. Sehn et al. Rapid infusion rituximab in combination with corticosteroid-containing chemotherapy or as maintenance therapy is well tolerated and can safely be delivered in the community setting. Blood 2007; 109:4171
  11. Tout et al. Rituximab exposure is influenced by baseline metabolic tumor volume and predicts outcome of DLBCL patients: a Lymphoma Study Association report. Blood 2017;129:2616(Suggests higher rituximab dose needed if metabolic tumor volume, determined by PET, is high)
  12. Niitsu et al. Prospective analysis of hepatitis B virus reactivation in patients with diffuse large B-cell lymphoma after rituximab combination chemotherapy. J Clin Oncol 2010;28:5097(12% of patients with evidence of prior HBV infection relapsed during or after rituximab treatment)
  13. Zurawska et al. Hepatitis B virus screening before chemotherapy for lymphoma: a cost-effectivness analysis. J Clin Oncol 2012;30:3167(Most cosf-effective to screen everyone; 10-fold decrease in HBV reactivation rate)
  14. Seto et al. Hepatitis B Reactivation in Patients With Previous Hepatitis B Virus Exposure Undergoing Rituximab-Containing Chemotherapy for Lymphoma: A Prospective Study. J Clin Oncol 2014;32:3736(41% reactivation rate in 2 yrs in anti-HBc positive patients with undetactable serum HBV DNA)
  15. Carson et al. Progressive multifocal leukoencephalopathy after rituximab therapy in HIV-negative patients: a report of 57 cases from the Research on Adverse Drug Events and Reports project. Blood 2009;113:4834
  16. Chakravarty et al. Pregnancy outcomes after maternal exposure to rituximab. Blood 2011;117:1499
  17. Yri et al. Rituximab blocks protective serologic response to influenza A (H1N1) 2009 vaccination in lymphoma patients during or within 6 months after treatment. Blood 2011;118:6769
  18. Sehn et al. A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies. Blood 2012;119:5118(GA101)
  19. Salles et al. Phase 1 study results of the type II glycoengineered humanized anti-CD20 monoclonal antibody obinutuzumab (GA101) in B-cell lymphoma patients. Blood 2012;119:5126
  20. Cartron and Watier. Obinutuzumab: what is there to learn from clinical trials? Blood 2017;130:581
  21. Crombie et al. Consensus recommendations on the management of toxicity associated with CD3×CD20 bispecific antibody therapy. Blood 2024;143:1565
  22. Teachey et al. Cytokine release syndrome after blinatumomab treatment related to abnormal macrophage activation and ameliorated with cytokine-directed therapy. Blood 2013;121:5154
  23. Velasquez et al. Redirecting T cells to hematological malignancies with bispecific antibodies. Blood 2018;131:30
  24. van de Donk et al. T-cell-engaging bispecific antibodies in cancer. Lancet 2023;402:142
  25. Rowe and Löwenberg. Gemtuzumab ozogamicin in acute myeloid leukemia: a remarkable saga about an active drug. Blood 2013;121:4838
  26. Appelbaum and Bernstein. Gemtuzumab ozogamicin for acute myeloid leukemia. Blood 2017;130:2373
  27. Ansell SM. Brentuximab vedotin. Blood 2014;124:3197
  28. Gandhi et al. Pancreatitis in patients treated with brentuximab vedotin: a previously unrecognized serious adverse event. Blood 2014;123:2895
  29. Wayne et al. Immunotoxins for leukemia. Blood 2014;123:2470
  30. Taylor and Lindorfer. Antibody-drug conjugate adverse effects can be understood and addressed based on immune complex clearance mechanisms. Blood 2024;144:137
  31. Taylor and Lindorfer. Fcγ-receptor–mediated trogocytosis impacts mAb-based therapies: historical precedence and recent developments. Blood 2015;125:762
  32. Handgretinger et al. Exploitation of natural killer cells for the treatment of acute leukemia. Blood 2016;127:3341
  33. de Mooij et al. Targeting the interleukin-1 pathway in patients with hematological disorders. Blood 2017;129:3155

CAR T-cells

  1. June and Sadelain. Chimeric Antigen Receptor Therapy. NEJM 2018;379:64
  2. Mause et al. Antibody-modified T cells: CARs take the front seat for hematologic malignancies. Blood 2014;123:2625
  3. Rosenberg and Restifo. Adoptive cell transfer as personalized immunotherapy for human cancer. Science 2015;348:62
  4. Morris and Stauss. Optimizing T-cell receptor gene therapy for hematologic malignancies. Blood 2016;127:3305
  5. Park et al. CD19-targeted CAR T-cell therapeutics for hematologic malignancies: interpreting clinical outcomes to date. Blood 2016;127:3312
  6. Ying et al. A safe and potent anti-CD19 CAR T cell therapy. Nat Med 2019;25:947 (Good anti-lymphoma activity, no neurotoxicity or severe CRS)
  7. Wang et al. Efficacy and safety of CAR19/22 T-cell cocktail therapy in patients with refractory/relapsed B-cell malignancies. Blood 2020;135:17(Dual-targeting to reduce antigen-escape relapse)
  8. Hill et al. Infectious complications of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy. Blood 2018;131:121(Incidence of infection similar to that after other salvage therapies; ALL, higher cell dose, severe CRS increased risk)
  9. Brudno and Kochenderfer. Toxicities of chimeric antigen receptor T cells: recognition and management. Blood 2016;127:3321
  10. Karschnia et al. Clinical presentation, management, and biomarkers of neurotoxicity after adoptive immunotherapy with CAR T cells. Blood 2019;133:2212
  11. Bhoj et al. Persistence of long-lived plasma cells and humoral immunity in individuals responding to CD19-directed CAR T-cell therapy. Blood 2016;128:360
  12. Lee et al. Current concepts in the diagnosis and management of cytokine release syndrome. Blood 2014;124:188
  13. Jain et al. How I treat refractory CRS and ICANS after CAR T-cell therapy. Blood 2023;141:2430
  14. Frigault et al. Itacitinib for the prevention of IEC therapy–associated CRS: results from the 2-part phase 2 INCB 39110-211 study. Blood 2025;146:422
  15. Wang et al. Coagulation Disorders after CAR T Cell Therapy: Analysis of 100 Patients with R/R Hematologic Malignancies. Biol Blood Bone Marrow Transplant 2019 (Epub)
  16. Peng et al. Coagulation abnormalities associated with CAR-T-cell therapy in haematological malignancies: A review. Br J Haematol 2024 (Epub)
  17. Lichtenstein et al. Characterization of HLH-like manifestations as a CRS variant in patients receiving CD22 CAR T cells. Blood 2021;138:2409
  18. Ganatra et al. Chimeric Antigen Receptor T-Cell Therapy–Associated Cardiomyopathy in Patients With Refractory or Relapsed Non-Hodgkin Lymphoma. Circulation 2020;142:1687
  19. Stefffin et al. Long-term follow-up for the development of subsequent malignancies in patients treated with genetically modified IECs. Blood 2022;140:16 (No evidence that these products cause second cancers)
  20. Deschênes-Simard et al. Clinical features, pathophysiology, and management of acute myelopathy following CAR T-cell therapy. Blood 2024;144:2083
  21. Jain et al. How I treat cytopenias after CAR T-cell therapy. Blood 2023;141:2460
  22. Guiterrez et al. How I approach optimization of patients at risk of cardiac and pulmonary complications after CAR T-cell therapy. Blood 2023;141:2452
  23. Santomasso et al. How I treat unique and difficult-to-manage cases of CAR T-cell therapy–associated neurotoxicity. Blood 2023;141:2443
  24. Rejeski et al. Immune effector cell–associated hematotoxicity: EHA/EBMT consensus grading and best practice recommendations. Blood 2023;142:865
  25. Hu and Dunbar. T-cell lymphomas in recipients of CAR-T cells: assessing risks and causalities. Blood 2024;144:2473
  26. Hamilton et al. Risk of Second Tumors and T-Cell Lymphoma after CAR T-Cell Therapy. NEJM 2024;390:2047 (With editorial)
  27. Ozdimirli et al. Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy. NEJM 2024;390:2074 (With editorial)
  28. Harrison et al. CAR+ T-Cell Lymphoma after Cilta-cel Therapy for Relapsed or Refractory Myeloma. NEJM 2025;392:677
  29. Perica et al. CD4+ T-Cell Lymphoma Harboring a Chimeric Antigen Receptor Integration in TP53. NEJM 2025;392:577

Immune checkpoint therapy

  1. Sharma and Allison. The future of immune checkpoint therapy. Science 2015;348:56
  2. Xu-Monette et al. PD-1 expression and clinical PD-1 blockade in B-cell lymphomas. Blood 2018;131:68
  3. Armand P. Immune checkpoint blockade in hematologic malignancies. Blood 2015;125:3393
  4. Keenan et al. Genomic correlates of response to immune checkpoint blockade. Nat Med 2019;25:389
  5. Sun et al. Utilizing cell-based therapeutics to overcome immune evasion in hematologic malignancies. Blood 2016;127:3350
  6. Vétizou et al. Anticancer immunotherapy by CTLA-4 blockade relies on the gut microbiota. Science 2015;350:1079(with editorial)
  7. Sivan et al. Commensal Bifidobacterium promotes antitumor immunity and facilitates anti–PD-L1 efficacy. Science 2015;350:1084(with editorial)
  8. Wang et al. Fatal Toxic Effects Associated With Immune Checkpoint Inhibitors. A Systematic Review and Meta-analysis. JAMA Oncol 2018;4:1721
  9. Wang et al. Fecal microbiota transplantation for refractory immune checkpoint inhibitor-associated colitis. Nat Med 2018;24:2018
  10. Ding and Chen. Predicting tumor response to PD-1 blockade. NEJM 2019;381:477
  11. Moik et al. Incidence, risk factors, and outcomes of venous and arterial thromboembolism in immune checkpoint inhibitor therapy. Blood 2021;137:1669
  12. Kroll et al. Hematologic complications of immune checkpoint inhibitors. Blood 2022;139:3594