Predictive significance of early bone marrow MRD response assessment in Acute Myeloid Leukemia patients treated with venetoclax plus decitabine induction therapy: Real-world data from India

Abstract INTRODUCTION The intensive 3+7 regimen is the standard induction therapy for acute myeloid leukemia (AML). However, a significant proportion of newly diagnosed AML patients are often ineligible for 3+7 induction therapy and are being treated with venetoclax (VEN) plus hypomethylating (decitabine/azacitidine) therapy. AIMS male: female ratio was 1:1.5. As per European LeukaemiaNet 2022 risk stratification, 27 %, 54 % and 19 % patients had favourable-, intermediate-, and adverse-risk AML, respectively. AML multiplex PCR was performed in all patients, and NGS could be performed in 14 % of the patients. The most frequent genetic abnormalities were FLT3 (24%), NPM1 (23%), RUNX1:RUNX1T1(13%), CBFB-MYH11 (6%), DNMT3A (6%), and NRAS (5%). Normal karyotype was noted in 50% of the patients, and the most frequent cytogenetic abnormality was t(8;21)(q22; q22.1)(9.73%), Monosomy 5(5.56%), Monosomy 7(4.17%), and inversion (16)(p13.1q22)(2.78 %). All patients had an ECOG performance status of 3 or 4. At presentation, the median hemoglobin, Total leucocyte counts, and platelets were 7.15 (g/dL), 37.39 x 109/L, and 47.16 x 109/L, respectively. At day 14, 22% of evaluable patients had marrow blasts 5 % & 8% had negative flow-MRD status. Ten percent of patients required a switch to intensive chemotherapy (7+3) based on day 14 marrow response. Either CR or CR with incomplete hematologic recovery (CRi) was achieved in 46% patients after two cycles of VEN+decitabine therapy, and 29% & 38 % achieved MRD negative status after cycle 1 & 2, respectively. Median time to nadir of hemoglobin, total leucocyte count, and platelet count from day 1 of VEN+decitabine therapy was 10, 13, and 9 days, respectively. The median interval between two consecutive cycles of VEN+HMA therapy was 40 (IQR 9) days. Thirteen percent of patients died in 1st cycle & another 4% died in 2nd cycle of VEN+decitabine. Thirty percent of patients required intensive chemotherapy after failure of VEN+decitabine, 29 % patients received high-dose cytarabine consolidation, and 25% patients opted for continuation of VEN+decitabine therapy. Matched sibling donor allogenic stem cell transplant was performed in three (4.2%) of the study population. Major leukemia-related complications at presentation were invasive fungal infection (77.8%), followed by tumor lysis syndrome (24%). Incidence of grade 4 anemia, thrombocytopenia, and febrile neutropenia in cycle 1 was 89%, 91%, and 64% respectively. The commonest non-hematological toxicity in cycle 1 was pneumonia (84%), septic shock (70%), & acute kidney injury (53%). After a median follow-up duration of 9 (IQR 4-14) months, 53 % patients are alive & 48 % continue to remain in complete remission. Twelve percent of patients had AML relapse. The median overall survival duration of the study was 17 months (95 % confidence interval (CI), 9-25 months). CONCLUSIONIn our single-centre experience, venetoclax plus decitabine induction therapy using generic preparations of venetoclax was observed to be highly effective & relatively safe in newly diagnosed AML patients who were considered ineligible for intensive induction regimens. VEN+decitabine therapy was associated with significant myelosuppression & delayed haematological recovery, but this could be effectively managed with intensive supportive treatment.