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Real-life data of azacitidine-venetoclax combination in acute myeloid leukemia patients: a single center experience

Year 2023, Volume: 6 Issue: 6, 1237 - 1243, 29.10.2023
https://doi.org/10.32322/jhsm.1359253

Abstract

Aims: To evaluate real-life data on the efficacy and safety of Venetoclax (Ven) therapy used in combination with hypomethylating agent (HMA) in patients with acute myeloid leukemia (AML).
Methods: The records of newly diagnosed, relapsed or refractory (RR) AML patients over 18 years of age who were planned to be treated with Azacitidine (AZA) combined with Ven because they were not suitable for intensive chemotherapy and patients who received AZA combined with Ven maintenance therapy after achieving remission were retrospectively analyzed. The standard protocol for patients is subcutaneous or intravenous AZA 75 mg/m2 on days 1-7/ every 28 days + oral Ven treatment 100-400 mg/day for 28 days. The treatment response rates, survival times, and side effect profiles of 18 newly diagnosed patients, 12 RR patients, and 4 patients receiving AZA+Ven as maintenance treatment between January 2021 and March 2022 were evaluated.
Results: It was found that 8 of the 34 patients (23.5%) who were examined in the present study died before the first response could be evaluated. When the response rates were evaluated, complete response (CR) or complete remission with incomplete blood count recovery (CRi) (CR+CRi) was found to be 61% in the group receiving AZA+Ven in the first line, and CR+CRi was 50% in the group receiving AZA+Ven because of RR AML. In the group receiving AZA+Ven in the first line, the average Overall Survival (OS) was 8.00 months (95% CI: 1.58-14.41), and 7.00 months in the RR group (95% CI: 1.78-12, 21). All patients in the group receiving AZA+Ven for maintenance purposes were alive and the median follow-up period was 12.50±6.02 months in this group (Mean±SD). The most common side effect was neutropenia, and the most common cause of death was disease progression.
Conclusion: In AML patients ineligible for intensive treatment due to advanced age or comorbidities, real-life data of AZA+Ven therapy with effective CR+CRi rates and a manageable spectrum of side effects promise hope.

Ethical Statement

Ethical approval by the Scientific Ethics Committee of Gülhane University of Health Sciences , Faculty of Medicine (date of ethics committee: 27.06.2022 decision number: 2022-249)

Supporting Institution

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References

  • Cavalcanti IDL, Soares JCS, Cavalcanti IDL, Soares JCS. Conventional Chemotherapy Versus Targeted Therapy. Advances in Cancer Treatment: From Systemic Chemotherapy to Targeted Therapy. 2021:79-89.
  • Sharma P, Pollyea DA. Shutting down acute myeloid leukemia and myelodysplastic syndrome with BCL-2 family protein inhibition. Curr Hematol Malig Rep. 2018;13(4):256-264.
  • Miranda-Filho A, Piñeros M, Ferlay J, Soerjomataram I, Monnereau A, Bray F. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol. 2018;5(1):e14-e24.
  • Dinardo CD. Hypomethylating agents and venetoclax in acute myeloid leukemia. Clin Adv Hematol Oncol. 2021;19(2):82-83.
  • Vasu S, Kohlschmidt J, Mrózek K, et al. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood Adv. 2018;2(13):1645-1650.
  • Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov. 2016;6(10):1106-1117.
  • Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24):4642-4649.
  • Clemmons A, Gandhi A, Clarke A, Jimenez S, Le T, Ajebo G. Premedications for cancer therapies: a primer for the hematology/oncology provider. J Adv Pract Oncol. 2021;12(8):810-832
  • DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17.
  • Maiti A, Rausch CR, Cortes JE, et al. Outcomes of relapsed or refractory acute myeloid leukemia after front-line hypomethylating agent and venetoclax regimens. Haematologica. 2021;106(3):894.
  • Yamamoto K, Shinagawa A, DiNardo CD, et al. Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Japan J Clin Oncol. 2022;52(1):29-38.
  • Brancati S, Gozzo L, Romano GL, et al. Venetoclax in relapsed/refractory acute myeloid leukemia: Are supporting evidences enough? Cancers. 2021;14(1):22.
  • 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.
  • 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.
  • Winters AC, Gutman JA, Purev E, et al. Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia. Blood Adv. 2019;3(20):2911-2919.
  • Jonas BA, Pollyea DA. How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia. Leukemia. 2019;33(12):2795-2804.
  • Jalbut MM, Chen EC, Hobbs GS, et al. The Impact of antimicrobial prophylaxis during induction chemotherapy for acute myeloid leukemia in the current era. Blood. 2017;130:2586.
  • Lee R, Cho S-Y, Lee D-G, et al. Infections of venetoclax-based chemotherapy in acute myeloid leukemia: rationale for proper antimicrobial prophylaxis. Cancers. 2021;13(24):6285.
  • DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19(2):216-228.
  • Pomares H, Arnan M, Sánchez‐Ortega I, Sureda A, Duarte RF. Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis? Mycoses. 2016;59(8):516-519.
  • Epstein DJ, Seo SK, Huang Y-T, et al. Micafungin versus posaconazole prophylaxis in acute leukemia or myelodysplastic syndrome: a randomized study. J Infect. 2018;77(3):227-234.
  • Agarwal SK, DiNardo CD, Potluri J, et al. Management of venetoclax-posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments. Clin Ther. 2017;39(2):359-367.
  • Azanza JR, Mensa J, Barberán J, et al. Recommendations on the use of azole antifungals in hematology-oncology patients. Revista Española de Quimioterapia. 2023;36(3):236.
  • Pollyea DA, Pratz KW, Jonas BA, et al. Venetoclax in combination with hypomethylating agents induces rapid, deep, and durable responses in patients with AML ineligible for intensive therapy. Blood. 2018;132:285.
Year 2023, Volume: 6 Issue: 6, 1237 - 1243, 29.10.2023
https://doi.org/10.32322/jhsm.1359253

Abstract

References

  • Cavalcanti IDL, Soares JCS, Cavalcanti IDL, Soares JCS. Conventional Chemotherapy Versus Targeted Therapy. Advances in Cancer Treatment: From Systemic Chemotherapy to Targeted Therapy. 2021:79-89.
  • Sharma P, Pollyea DA. Shutting down acute myeloid leukemia and myelodysplastic syndrome with BCL-2 family protein inhibition. Curr Hematol Malig Rep. 2018;13(4):256-264.
  • Miranda-Filho A, Piñeros M, Ferlay J, Soerjomataram I, Monnereau A, Bray F. Epidemiological patterns of leukaemia in 184 countries: a population-based study. Lancet Haematol. 2018;5(1):e14-e24.
  • Dinardo CD. Hypomethylating agents and venetoclax in acute myeloid leukemia. Clin Adv Hematol Oncol. 2021;19(2):82-83.
  • Vasu S, Kohlschmidt J, Mrózek K, et al. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood Adv. 2018;2(13):1645-1650.
  • Konopleva M, Pollyea DA, Potluri J, et al. Efficacy and biological correlates of response in a phase II study of venetoclax monotherapy in patients with acute myelogenous leukemia. Cancer Discov. 2016;6(10):1106-1117.
  • Cheson BD, Bennett JM, Kopecky KJ, et al. Revised recommendations of the international working group for diagnosis, standardization of response criteria, treatment outcomes, and reporting standards for therapeutic trials in acute myeloid leukemia. J Clin Oncol. 2003;21(24):4642-4649.
  • Clemmons A, Gandhi A, Clarke A, Jimenez S, Le T, Ajebo G. Premedications for cancer therapies: a primer for the hematology/oncology provider. J Adv Pract Oncol. 2021;12(8):810-832
  • DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17.
  • Maiti A, Rausch CR, Cortes JE, et al. Outcomes of relapsed or refractory acute myeloid leukemia after front-line hypomethylating agent and venetoclax regimens. Haematologica. 2021;106(3):894.
  • Yamamoto K, Shinagawa A, DiNardo CD, et al. Venetoclax plus azacitidine in Japanese patients with untreated acute myeloid leukemia ineligible for intensive chemotherapy. Japan J Clin Oncol. 2022;52(1):29-38.
  • Brancati S, Gozzo L, Romano GL, et al. Venetoclax in relapsed/refractory acute myeloid leukemia: Are supporting evidences enough? Cancers. 2021;14(1):22.
  • 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.
  • 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.
  • Winters AC, Gutman JA, Purev E, et al. Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia. Blood Adv. 2019;3(20):2911-2919.
  • Jonas BA, Pollyea DA. How we use venetoclax with hypomethylating agents for the treatment of newly diagnosed patients with acute myeloid leukemia. Leukemia. 2019;33(12):2795-2804.
  • Jalbut MM, Chen EC, Hobbs GS, et al. The Impact of antimicrobial prophylaxis during induction chemotherapy for acute myeloid leukemia in the current era. Blood. 2017;130:2586.
  • Lee R, Cho S-Y, Lee D-G, et al. Infections of venetoclax-based chemotherapy in acute myeloid leukemia: rationale for proper antimicrobial prophylaxis. Cancers. 2021;13(24):6285.
  • DiNardo CD, Pratz KW, Letai A, et al. Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study. Lancet Oncol. 2018;19(2):216-228.
  • Pomares H, Arnan M, Sánchez‐Ortega I, Sureda A, Duarte RF. Invasive fungal infections in AML/MDS patients treated with azacitidine: a risk worth considering antifungal prophylaxis? Mycoses. 2016;59(8):516-519.
  • Epstein DJ, Seo SK, Huang Y-T, et al. Micafungin versus posaconazole prophylaxis in acute leukemia or myelodysplastic syndrome: a randomized study. J Infect. 2018;77(3):227-234.
  • Agarwal SK, DiNardo CD, Potluri J, et al. Management of venetoclax-posaconazole interaction in acute myeloid leukemia patients: evaluation of dose adjustments. Clin Ther. 2017;39(2):359-367.
  • Azanza JR, Mensa J, Barberán J, et al. Recommendations on the use of azole antifungals in hematology-oncology patients. Revista Española de Quimioterapia. 2023;36(3):236.
  • Pollyea DA, Pratz KW, Jonas BA, et al. Venetoclax in combination with hypomethylating agents induces rapid, deep, and durable responses in patients with AML ineligible for intensive therapy. Blood. 2018;132:285.

Details

Primary Language English
Subjects Haematology, Clinical Oncology, Chemotherapy
Journal Section Original Article
Authors

Tuba BULDUK 0000-0001-9549-5904

Melda CÖMERT 0000-0002-7798-4349

Ebru KILIÇ 0000-0001-8663-3172

Selim SAYIN 0000-0002-7197-6890

Murat YILDIRIM 0000-0001-6416-9575

Meltem AYLI 0000-0001-5766-5642

Early Pub Date October 28, 2023
Publication Date October 29, 2023
Published in Issue Year 2023 Volume: 6 Issue: 6

Cite

AMA BULDUK T, CÖMERT M, KILIÇ E, SAYIN S, YILDIRIM M, AYLI M. Real-life data of azacitidine-venetoclax combination in acute myeloid leukemia patients: a single center experience. J Health Sci Med / JHSM. October 2023;6(6):1237-1243. doi:10.32322/jhsm.1359253

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