Journal of Internal Medicine Concepts & Practice >
Clinical observation of the combination therapy of azacitidine and venetoclax in newly diagnosed, elderly patients with acute myeloid leukemia
Received date: 2021-01-11
Online published: 2022-07-26
Objective To observe the clinical efficacy and safety of azacitidine combined with venetoclax in the treatment of newly diagnosed, elderly patients with acute myeloid leukemia (AML). Methods Fourteen elderly patients admitted in Ruijin Hospital from March 2018 to September 2020, who were newly diagnosed with AML and not suitable for intensive chemotherapy, were enrolled and a retrospective analysis was conducted. All patients received 75 mg/m2 azacitidine subcutaneously from day 1 to day 7, and venetoclax orally once a day, total 28 d(the first cause of venetoclax treatment: 100 mg in day 1, 200 mg in day 2, 400 mg from day 3 to day 28). The primary end points were composite complete remission rate (CR+CRi), overall response rate (ORR), time to first response(CR/CRi ) and duration of response (DOR), and the secondary end points were overall survival(OS) and safety. Results The median follow-up time was 12.5 (2.0-24.0) months, the composite complete remission rate (CR+CRi) was 71%, ORR was 79%, the median time to first response was 1.1 (1.0-2.1) months, the median DOR was 16.0 months [95% confidence interval (CI): 4.0-not reached(NR)], and the median OS was 14.0 months (95% CI: 4.0-NR). Among 12 patients with median and high danger of poor cytogenetics, 8 patients (67%) achieved CR+CRi, the median DOR was 9.0 months (95% CI: 2.0-NR), and the median OS was 11.0 months (95% CI: 2.0-NR). Among 10 patients with CR + CRi, 8 patients(80%) achieved MRD<0.01% at least in one assessment, the median DOR was 17.0 months (95% CI: 4.0-NR) and the median OS did not reach (95% CI: 6.0-NR）。All patients showed cytopenia in different degree, including neutropenia of grade 3 or above (100%), thrombocytopenia (7 cases, 50%), febrile neutropenia (6 cases, 43%) and anemia (5 cases, 36%). The other common events occurred in gastrointestinal tract, which were all controllable response of grade 1-2. One patient showed tumor lysis syndrome. Most patients were tolerant to treatment. Conclusions The preliminary results show that the combination therapy of azacitidine and venetoclax is effective and safe, which provides a treatment option for elderly, untreated AML patients who are not suitable for intensive chemotherapy.
Key words： Acute myeloid leukemia; Elderly; Newly diagnosed; Azacitidine; Venetoclax
HUANG Lei, YE Chenjing, WU Chao, XU Wenbin, YU Qing, LI Junmin, YAN Hua . Clinical observation of the combination therapy of azacitidine and venetoclax in newly diagnosed, elderly patients with acute myeloid leukemia[J]. Journal of Internal Medicine Concepts & Practice, 2021 , 16(03) : 178 -182 . DOI: 10.16138/j.1673-6087.2021.03.008
| [1] | Estey E, Karp JE, Emadi A, et al. Recent drug approvals for newly diagnosed acute myeloid leukemia: gifts or a Trojan horse[J]?. Leukemia, 2020, 34(3): 671-681. |
| [2] | 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[J]. Lancet Oncol, 2018, 19(2): 216-228. |
| [3] | DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia[J]. Blood, 2019, 133(1): 7-17. |
| [4] | Arber DA, Orazi A, Hasserjian R, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia[J]. Blood, 2016, 128(3): 462-463. |
| [5] | 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]. J Clin Oncol, 2003, 21(24): 4642-4649. |
| [6] | Howlader N, Noone AM, Krapcho M, et al. SEER cancer statistics review, 1975-2016[EB/OL]. Bethesda, MD: National Cancer Institute,2019. https://seer.cancer.gov/csr/1975_2016/. |
| [7] | Fenaux P, Mufti GJ, Hellström-Lindberg E, et al. Azacitidine prolongs overall survival compared with conventional care regimens in elderly patients with low bone marrow blast count acute myeloid leukemia[J]. J Clin Oncol, 2010, 28(4): 562-569. |
| [8] | Pleyer L, Burgstaller S, Girschikofsky M, et al. Azacitidine in 302 patients with WHO-defined acute myeloid leukemia: results from the Austrian Azacitidine Registry of the AGMT-Study Group[J]. Ann Hematol, 2014, 93(11): 1825-1838. |
| [9] | 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[J]. Blood, 2015, 126(3): 291-299. |
| [10] | 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[J]. Cancer Discov, 2016, 6(10): 1106-1117. |
| [11] | Bogenberger JM, Delman D, Hansen N, et al. Ex vivo activity of BCL-2 family inhibitors ABT-199 and ABT-737 combined with 5-azacytidine in myeloid malignancies[J]. Leuk Lymphoma, 2015, 56(1): 226-229. |
| [12] | Bose P, Gandhi V, Konopleva M. Pathways and mechanisms of venetoclax resistance[J]. Leuk Lymphoma, 2017, 58(9): 1-17. |
| [13] | Teh TC, Nguyen NY, Moujalled DM, et al. Enhancing venetoclax activity in acute myeloid leukemia by co-targeting MCL1[J]. Leukemia, 2018, 32(2): 303-312. |
| [14] | DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia[J]. N Engl J Med, 2020, 383(7): 617-629. |
| [15] | Davids MS, Hallek M, Wierda W, et al. Comprehensive safety analysis of venetoclax monotherapy for patients with relapsed/refractory chronic lymphocytic leukemia[J]. Clin Cancer Res, 2018, 24(18): 4371-4379. |
/
| 〈 |
|
〉 |
