Vol 12, No 3-4 (2021)
Review paper
Published online: 2022-02-18

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Adverse events of monoclonal antibodies use in therapy of hematological malignancies

Marcela Maksymowicz1, Monika Podhorecka2
Hematology in Clinical Practice 2021;12(3-4):121-131.

Abstract

Monoclonal antibodies given as monotherapy or combination therapy have emerged as effective treatment options for hematologic malignancies. By prolonging survival, mAbs reduced mortality and improved the clinical prognosis for patients with these diseases. However, despite the effective anticancer activity of mAbs, they induce adverse events. The most common side effects are infusion related reactions (IRR), associated with cytokine release within the first few hours after administration. IRR are usually mild to moderate and manifest in rash, fever, nausea, vomiting, dizziness, headache, hypotension or tachycardia. Other, common toxicities are cytopenias, increasing the risk of infections and bleeding. Most preventive strategies involve the use of glucocorticosteroids, acetaminophen, antihistamines, screening for antibodies against microorganisms and prophylaxis for infections. Cytokine release syndrome, cardiac, pulmonary, neurologic adverse effects occur less frequently. In cases of grade 1–2 toxicity, symptomatic management is recommended, but in more severe symptoms temporary or permanent discontinuation of therapy and use of glucocorticosteroids are recommended. In an effort to limit the incidence and severity of adverse events clinicians should know how to early recognize, precisely assess and timely manage.

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References

  1. Shah M, Rajha E, DiNardo C, et al. Adverse events of novel therapies for hematologic malignancies: what emergency physicians should know. Ann Emerg Med. 2020; 75(2): 264–286.
  2. Golay J, Taylor RP. The role of complement in the mechanism of action of therapeutic anti-cancer mAbs. Antibodies (Basel). 2020; 9(4).
  3. Constantinescu C, Pasca S, Zimta AA, et al. Overview of the side-effects of FDA- and/or EMA-approved targeted therapies for the treatment of hematological malignancies. J Clin Med. 2020; 9(9).
  4. Salles G, Barrett M, Foà R, et al. Rituximab in B-cell hematologic malignancies: a review of 20 years of clinical experience. Adv Ther. 2017; 34(10): 2232–2273.
  5. Yelvington BJ. Subcutaneous rituximab in follicular lymphoma, chronic lymphocytic leukemia, and diffuse large B-cell lymphoma. J Adv Pract Oncol. 2018; 9(5): 530–534.
  6. Ruiz-Camps I, Aguilar-Company J. Risk of infection associated with targeted therapies for solid organ and hematological malignancies. Ther Adv Infect Dis. 2021; 8: 2049936121989548.
  7. Varma P, Falconer J, Aga A, et al. Rituximab-induced Crohn's disease. Scand J Gastroenterol. 2017; 52(5): 606–608.
  8. Urru SAM, Spila Alegiani S, Guella A, et al. Safety of switching between rituximab biosimilars in onco-hematology. Sci Rep. 2021; 11(1): 5956.
  9. Freeman CL, Sehn LH. A tale of two antibodies: obinutuzumab versus rituximab. Br J Haematol. 2018; 182(1): 29–45.
  10. Amitai I, Gafter-Gvili A, Shargian-Alon L, et al. Obinutuzumab-related adverse events: a systematic review and meta-analysis. Hematol Oncol. 2021; 39(2): 215–221.
  11. Samuels C, Abbott D, Niemiec S, et al. Evaluation and associated risk factors for neutropenia with venetoclax and obinutuzumab in the treatment of chronic lymphocytic leukemia. Cancer Rep (Hoboken). 2021 [Epub ahead of print]: e1505.
  12. Gao S, Zhang M, Wu K, et al. Risk of adverse events in lymphoma patients treated with brentuximab vedotin: a systematic review and meta-analysis. Expert Opin Drug Saf. 2020; 19(5): 617–623.
  13. Fargeot G, Dupel-Pottier C, Stephant M, et al. Brentuximab vedotin treatment associated with acute and chronic inflammatory demyelinating polyradiculoneuropathies. J Neurol Neurosurg Psychiatry. 2020; 91(7): 786–788.
  14. Makita S, Maruyama D, Tobinai K. Safety and efficacy of brentuximab vedotin in the treatment of classic Hodgkin lymphoma. Onco Targets Ther. 2020; 13: 5993–6009.
  15. Moskowitz AJ. Optimizing the role of brentuximab vedotin in classical Hodgkin lymphoma therapy. Hematology Am Soc Hematol Educ Program. 2018; 2018(1): 207–212.
  16. Cheson BD, Bartlett NL, LaPlant B, et al. Brentuximab vedotin plus nivolumab as first-line therapy in older or chemotherapy-ineligible patients with Hodgkin lymphoma (ACCRU): a multicentre, single-arm, phase 2 trial. Lancet Haematol. 2020; 7(11): e808–e815.
  17. Conde-Royo D, Juárez-Salcedo LM, Dalia S. Management of adverse effects of new monoclonal antibody treatments in acute lymphoblastic leukemia. Drugs Context. 2020; 9.
  18. Sigmund AM, Sahasrabudhe KD, Bhatnagar B. Evaluating blinatumomab for the treatment of relapsed/refractory ALL: design, development, and place in therapy. Blood Lymphat Cancer. 2020; 10: 7–20.
  19. Gavralidis A, Brunner AM. Novel therapies in the treatment of adult acute lymphoblastic leukemia. Curr Hematol Malig Rep. 2020; 15(4): 294–304.
  20. Topp MS, Stein AS, Gökbuget N, et al. Blinatumomab as first salvage versus second or later salvage in adults with relapsed/refractory B-cell precursor acute lymphoblastic leukemia: Results of a pooled analysis. Cancer Med. 2021; 10(8): 2601–2610.
  21. Li X, Zhou M, Qi J, et al. Efficacy and safety of inotuzumab ozogamicin (CMC-544) for the treatment of relapsed/refractory acute lymphoblastic leukemia and non-Hodgkin lymphoma: a systematic review and meta-analysis. Clin Lymphoma Myeloma Leuk. 2021; 21(3): e227–e247.
  22. Corbacioglu S, Jabbour EJ, Mohty M. Risk factors for development of and progression of hepatic veno-occlusive disease/sinusoidal obstruction syndrome. Biol Blood Marrow Transplant. 2019; 25(7): 1271–1280.
  23. Aujla A, Aujla R, Liu D. Inotuzumab ozogamicin in clinical development for acute lymphoblastic leukemia and non-Hodgkin lymphoma. Biomark Res. 2019; 7: 9.
  24. Muhamad NA, Mohd Dali NS, Mohd Yacob A, et al. Effect and safety of gemtuzumab ozogamicin for the treatment of patients with acute myeloid leukaemia: a systematic review protocol. BMJ Open. 2020; 10(6): e032503.
  25. Pautas C, Raffoux E, Lambert J, et al. Fractionated doses of gemtuzumab ozogamicin with escalated doses of daunorubicin and cytarabine as first acute myeloid leukemia salvage in patients aged 50-70-year old: a phase 1/2 study of the acute leukemia French association. Am J Hematol. 2012; 87(1): 62–65.
  26. Molica M, Perrone S, Mazzone C, et al. CD33 Expression and gentuzumab ozogamicin in acute myeloid leukemia: two sides of the same coin. Cancers (Basel). 2021; 13(13).
  27. Cortes JE, de Lima M, Dombret H, et al. Prevention, recognition, and management of adverse events associated with gemtuzumab ozogamicin use in acute myeloid leukemia. J Hematol Oncol. 2020; 13(1): 137.
  28. Vollmar BS, Frantz C, Schutten MM, et al. Calicheamicin antibody-drug conjugates with improved properties. Mol Cancer Ther. 2021; 20(6): 1112–1120.
  29. Dima D, Dower J, Comenzo RL, et al. Evaluating daratumumab in the treatment of multiple myeloma: safety, efficacy and place in therapy. Cancer Manag Res. 2020; 12: 7891–7903.
  30. Offidani M, Corvatta L, Morè S, et al. Daratumumab for the management of newly diagnosed and relapsed/refractory multiple myeloma: current and emerging treatments. Front Oncol. 2020; 10: 624661.
  31. Morè S, Petrucci MT, Corvatta L, et al. Monoclonal antibodies: leading actors in the relapsed/refractory multiple myeloma treatment. Pharmaceuticals (Basel). 2020; 13(12).
  32. Zhang T, Wang S, Lin T, et al. Systematic review and meta-analysis of the efficacy and safety of novel monoclonal antibodies for treatment of relapsed/refractory multiple myeloma. Oncotarget. 2017; 8(20): 34001–34017.
  33. Dimopoulos MA, Lonial S, Betts KA, et al. Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 4-year follow-up and analysis of relative progression-free survival from the randomized ELOQUENT-2 trial. Cancer. 2018; 124(20): 4032–4043.
  34. Ransohoff JD, Kwong BY. Cutaneous adverse events of targeted therapies for hematolymphoid malignancies. Clin Lymphoma Myeloma Leuk. 2017; 17(12): 834–851.
  35. Sharma K, Janik JE, O'Mahony D, et al. Phase II study of alemtuzumab (CAMPATH-1) in patients with HTLV-1-associated adult T-cell leukemia/lymphoma. Clin Cancer Res. 2017; 23(1): 35–42.
  36. Alpdogan O, Kartan S, Johnson W, et al. Allogeneic hematopoietic stem cell transplantation in advanced stage mycosis fungoides and Sézary syndrome: a concise review. Chin Clin Oncol. 2019; 8(1): 12.
  37. Wulf GG, Altmann B, Ziepert M, et al. ACT-2 study investigators. Alemtuzumab plus CHOP versus CHOP in elderly patients with peripheral T-cell lymphoma: the DSHNHL2006-1B/ACT-2 trial. Leukemia. 2021; 35(1): 143–155.
  38. Lenihan DJ, Alencar AJ, Yang D, et al. Cardiac toxicity of alemtuzumab in patients with mycosis fungoides/Sézary syndrome. Blood. 2004; 104(3): 655–658.
  39. Lloyd R, Nikolousis E, Kishore B, et al. Autoimmune cytopenias developing late post alemtuzumab-based allogeneic stem cell transplantation: presentation of short case series from a transplant center. Cell Transplant. 2020; 29: 963689720950641.
  40. Ollila TA, Sahin I, Olszewski AJ. Mogamulizumab: a new tool for management of cutaneous T-cell lymphoma. Onco Targets Ther. 2019; 12: 1085–1094.
  41. Blackmon AL, Pinter-Brown L. Spotlight on mogamulizumab-Kpkc for use in adults with relapsed or refractory mycosis fungoides or Sézary syndrome: efficacy, safety, and patient selection. Drug Des Devel Ther. 2020; 14: 3747–3754.
  42. Moore DC, Elmes JB, Shibu PA, et al. Mogamulizumab: sn snti-CC chemokine receptor 4 antibody for T-cell lymphomas. Ann Pharmacother. 2020; 54(4): 371–379.
  43. Alatrash G, Daver N, Mittendorf EA. Targeting immune checkpoints in hematologic malignancies. Pharmacol Rev. 2016; 68(4): 1014–1025.
  44. Matsuki E, Younes A. Checkpoint inhibitors and other immune therapies for Hodgkin and non-Hodgkin lymphoma. Curr Treat Options Oncol. 2016; 17(6): 31.
  45. Hradska K, Hajek R, Jelinek T. Toxicity of immune-checkpoint inhibitors in hematological malignancies. Front Pharmacol. 2021; 12: 733890.
  46. Bewersdorf JP, Stahl M, Zeidan AM. Immune checkpoint-based therapy in myeloid malignancies: a promise yet to be fulfilled. Expert Rev Anticancer Ther. 2019; 19(5): 393–404.
  47. Stahl M, Goldberg AD. Immune checkpoint inhibitors in acute myeloid leukemia: novel combinations and therapeutic targets. Curr Oncol Rep. 2019; 21(4): 37.
  48. Usmani SZ, Schjesvold F, Oriol A, et al. KEYNOTE-185 Investigators. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019; 6(9): e448–e458.



Hematology in Clinical Practice