Venetoclax and Azacitidine Therapy in Elder Acute Myeloid Leukemia: A Retrospective Evaluation of Real-World Experience

Abstract Background：To investigate the efficacy of venetoclax combined with azacytidine in the treatment of elderly patients with relapsed and refractory (R/R) acute myeloid leukemia（AML). Methods： The clinical data of 9 elderly AML patients over 65 years old, including 5 with R/R AML, using venetoclax and azacytidine were retrospectively analyzed. Results： Six males and 3 females with a median age of 71 years were included in this study, of which four patients had at least one relapse, and one patient did not get go into remission after 4 cycles of azacytidine monotherapy, deeming it refractory. Four patients had AML with myelodysplasia-related changes (AML-MRC). After 1 to 13 cycles of treatment using venetoclax and azacytidine, one of the 9 patients died early due to long duration of neutropenia and severe pulmonary infection caused by drugs. and six of the remaining 8 patients obtained complete response or complete response with incomplete hematologic recovery (CR/ CRi) , including five R/R patients. One patient did not respond to treatment after two cycles. For the side effects of the treatment, granulocytopenia occurred in all patients, and neutropenia occurred in 8 patients, lasting for an average of 10.5 (6-15) days and was most obvious in the second to third week of treatment. Three patients with TP53 gene mutation positive had following different outcomes. One relapsed patient achieved progression free remission (PFS) for 16 months up to date, and a second patient achieved complete remission but relapsed two months thereafter. Another patient had complete remission in myelology for 4months, but the variant allele fraction value (VAF) gradually increased, indicative that the disease was about to progress. Conclusion：Venetoclax combined with azacytidine regimen in elderly patients is an effective and well tolerated rescue scheme for R/R AML.The patients with TP53 mutation with lower VAF may be benifit from Venetoclax and azacytidine. Severe infection caused by neutropenia is an adverse reaction worthy of attention in the treatment process of the regimen.