The efficacy and safety of venetoclax-based and anthracycline-free induction therapy followed by allogeneic hematopoietic stem cell transplantation in the treatment of transplant-eligible Acute Myeloid Leukemia patients

Abstract

Abstract Background The standard treatment of transplant-eligible acute myeloid leukemia is intensive anthracycline plus cytarabine (3 + 7) followed by allogeneic hematopoietic stem cell transplantation. However, intensive induction treatment-related morbidity, mortality, and postponement or inability to transition to transplant are to be considered. Randomized phase 3 trials supported the treatment of venetoclax plus azacitidine or low-dose cytarabine in unfit or elderly patients. We investigate the efficacy, safety, and transition rate to allotransplant in transplant-eligible AML patients. Method The induction therapy included venetoclax plus a standard dose of cytarabine (venetoclax 100 mg plus posaconazole 300 mg per day until remission; cytarabine 100 mg/m2/day x 7), or venetoclax plus azacitidine (venetoclax 100 mg plus posaconazole 300 mg per day until remission; azacitidine 75 mg/m2/d x 7). The consolidation therapy included the same dose of induction therapy. We also investigated 63 AML patients who were younger than 65 and who had the intention to transplant, were treated with traditional 3 + 7 induction therapy, and then were transplanted at our institute between 2012 and 2018. Results Between 2019 and 2024, we treated 24 consecutive transplant-eligible AML patients with venetoclax plus a standard dose of cytarabine in 19 and venetoclax plus azacitidine in 5 patients. Male to female was 10 and 14 (42% vs 58%). Fifteen of whom had high-risk (62.5%) according to cytogenetic, mutation, or therapy-related factors, including nine therapy-related AML (37.5%) and one MDS/MPN-transformed (4.2%). Three therapy-related patients (one myeloma and two lymphoblastic lymphoma patients) have undergone high-dose chemotherapy and autologous hematopoietic stem cell transplantation, and one (AML patient) underwent an allogeneic transplant with an elapse time of 10 years. One patient was refractory, and the other twenty-three patients achieved complete remission, but two of them relapsed in 3 and 6 months after induction (durable CR rate 87.5%), with median time to best response 35 days and median duration of remission 747 days. Twenty-one patients proceeded to allogeneic hematopoietic stem cell transplant (transition to transplant rate 87.5%). The three- and five-year disease-free and overall survival rates were 60%/60% and 49%/48%, respectively. Two non-relapse mortalities occurred (one suffocation and one idiopathic pneumonia), and one died of a second lung cancer 43 months after AML. One patient had oral mucositis, and no patient had severe diarrhea. As compared with our previous 3 + 7 therapy database, the median age of venetoclax-based and traditional 3 + 7 was 56 vs 57 years of age, 60-day mortality was 0% vs 22%, and transition to transplant rate was 87.5% vs 33.0%. Three- and five-year overall survival was 60% vs 20% and 48% vs 19%, respectively (p < 0.001), and five-year overall survival after allo-transplant was 48% vs 57%. Conclusion This is the first feasible experience of a venetoclax-based and anthracycline-free regimen followed by allogeneic hematopoietic stem cell transplantation in the treatment of transplant-eligible AML patients with a significantly higher remission rate, transition to transplant rate, and overall survival as compared with traditional 3 + 7 followed by allotransplant. But there was no significant difference in terms of overall survival when either induction therapy was followed by allogeneic hematopoietic stem cell transplantation.