Vol 14 (2023): Continuous Publishing
Review paper
Published online: 2023-04-28

open access

Page views 2438
Article views/downloads 1749
Get Citation

Connect on Social Media

Connect on Social Media

How do I manage the myelotoxicity of venetoclax and azacitidine in patients with newly diagnosed acute myeloid leukemia?

Aleksander Salomon-Perzyński1, Bożena Katarzyna Budziszewska1
Hematology in Clinical Practice 2023;14:6-10.

Abstract

The introduction of venetoclax in combination with azacitidine (venAZA) represents a turning point in the treatment of patients with newly diagnosed acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy due to age, performance status and/or significant comorbidities. Conducting venAZA treatment in routine clinical practice, however, can present significant difficulties, due to both the substantial myelotoxicity (severe hematological side effects during venAZA are experienced by the majority of patients) and the clinical characteristics of AML patients not eligible for intensive chemotherapy. Thus, for optimal treatment outcomes, appropriate patient qualification for treatment and robust management of venAZA hematological toxicity are crucial. Retrospective data indicate that modification of venetoclax and azacitidine dosing during treatment is associated with longer treatment duration and translates favourably into longer overall survival. Here, the authors outline the management of patients with newly diagnosed AML in whom treatment with venAZA is complicated by profound myelosuppression.

Article available in PDF format

View PDF Download PDF file

References

  1. Herold T, Rothenberg-Thurley M, Grunwald VV, et al. Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia. Leukemia. 2020; 34(12): 3161–3172.
  2. Kantarjian HM, Thomas XG, Dmoszynska A, et al. Multicenter, randomized, open-label, phase III trial of decitabine versus patient choice, with physician advice, of either supportive care or low-dose cytarabine for the treatment of older patients with newly diagnosed acute myeloid leukemia. J Clin Oncol. 2012; 30(21): 2670–2677.
  3. Dombret H, Seymour JF, Butrym A, et al. International phase 3 study of azacitidine vs conventional care regimens in older patients with newly diagnosed AML with >30% blasts. Blood. 2015; 126(3): 291–299.
  4. Budziszewska BK, Salomon-Perzyński A, Pruszczyk K, et al. Cladribine combined with low-dose cytarabine as frontline treatment for unfit elderly acute myeloid leukemia patients: results from a prospective multicenter study of Polish Adult Leukemia Group (PALG). Cancers (Basel). 2021; 13(16).
  5. Kadia TM, Cortes J, Ravandi F, et al. Cladribine and low-dose cytarabine alternating with decitabine as front-line therapy for elderly patients with acute myeloid leukaemia: a phase 2 single-arm trial. Lancet Haematol. 2018; 5(9): e411–e421.
  6. DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020; 383(7): 617–629.
  7. Pratz KW, Jonas BA, Pullarkat VA, et al. Long-term follow-up of the phase 3 viale — a clinical trial of venetoclax plus azacitidine for patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Blood. 2022; 140(Suppl 1): 529–531.
  8. Pratz KW, DiNardo CD, Selleslag D, et al. Postremission cytopenia management in patients with acute myeloid leukemia treated with venetoclax and azacitidine in VIALE-A. Am J Hematol. 2022; 97(11): E416–E419.
  9. DiNardo CD, Wei AH. How I treat acute myeloid leukemia in the era of new drugs. Blood. 2020; 135(2): 85–96.
  10. Döhner H, Wei AH, Appelbaum FR, et al. Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN. Blood. 2022; 140(12): 1345–1377.
  11. On S, Rath CG, Lan M, et al. Characterisation of infections in patients with acute myeloid leukaemia receiving venetoclax and a hypomethylating agent. Br J Haematol. 2022; 197(1): 63–70.
  12. Arora S, Zainaldin C, Bathini S, et al. Tumor lysis syndrome and infectious complications during treatment with venetoclax combined with azacitidine or decitabine in patients with acute myeloid leukemia. Leuk Res. 2022; 117: 106844.
  13. Zhang A, Johnson T, Abbott D, et al. Incidence of invasive fungal infections in patients with previously untreated acute myeloid leukemia receiving venetoclax and azacitidine. Open Forum Infect Dis. 2022; 9(10): ofac486.
  14. Chen EC, Liu Y, Harris CE, et al. Outcomes of antifungal prophylaxis for newly diagnosed AML patients treated with a hypomethylating agent and venetoclax. Leuk Lymphoma. 2022; 63(8): 1934–1941.
  15. Wang ST, Chou CH, Chen TT, et al. High rate of invasive fungal infections during early cycles of azacitidine for patients with acute myeloid leukemia. Front Cell Infect Microbiol. 2022; 12: 1012334.
  16. Stemler J, de Jonge N, Skoetz N, et al. Antifungal prophylaxis in adult patients with acute myeloid leukaemia treated with novel targeted therapies: a systematic review and expert consensus recommendation from the European Hematology Association. Lancet Haematol. 2022; 9(5): e361–e373.
  17. Venclyxto. European Medicines Agency. https://www.ema.europa.eu/en/medicines/human/EPAR/venclyxto (February 12, 2023).
  18. Rausch CR, DiNardo CD, Maiti A, et al. Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia. Cancer. 2021; 127(14): 2489–2499.
  19. Willekens C, Chraibi S, Decroocq J, et al. Reduced venetoclax exposition to seven days of azacitidine is efficient in treatment-naïve patients with acute myeloid leukemia. Blood. 2022; 140(Suppl 1): 537–538.
  20. Vachhani P, Flahavan EM, Xu T, et al. Venetoclax and hypomethylating agents as first-line treatment in newly diagnosed patients with AML in a predominately community setting in the US. Oncologist. 2022; 27(11): 907–918.
  21. Aiba M, Shigematsu A, Suzuki T, et al. Shorter duration of venetoclax administration to 14 days has same efficacy and better safety profile in treatment of acute myeloid leukemia. Ann Hematol. 2023; 102(3): 541–546.
  22. Kang KW, Kim DS, Lee SeR, et al. Effect of granulocyte colony-stimulating factor on outcomes in patients with non-M3 acute myelogenous leukemia treated with anthracycline-based induction (7+3 regimen) chemotherapies. Leuk Res. 2017; 57: 1–8.
  23. DiNardo C, Pratz K, Panayiotidis P, et al. AML-119 the impact of post-remission granulocyte colony-stimulating factor (G-CSF) use (G-CSFu) in the phase 3 studies of venetoclax (Ven) combination treatments in patients (Pts) with newly diagnosed acute myeloid leukemia (AML). Clin Lymphoma Myeloma Leuk. 2022; 22: S214.