Comparative Efficacy of Venetoclax-based Combination Therapies and Other Therapies in Treatment Naïve Patients with Acute Myeloid Leukemia (AML) Ineligible for Intensive Chemotherapy: A Network Meta-Analysis

This network meta-analysis (NMA) assessed the efficacy of VEN + azacitidine [VEN+AZA] and VEN + low-dose cytarabine [VEN+LDAC] compared to AZA, LDAC, and decitabine (DEC) monotherapies, and best supportive care (BSC), in adults with untreated acute myeloid leukemia (AML) ineligible for intensive chemotherapy.A systematic literature review and feasibility assessment was conducted to select phase III, randomized, controlled trials for inclusion in the NMA. Complete remission + complete remission with incomplete blood count recovery [CR+CRi], and overall survival (OS) were compared using a Bayesian fixed-effects NMA. Treatments were ranked using surface under cumulative ranking curves (SUCRA) with higher values indicating a higher likelihood of being effective.A total of 1,140 patients across five trials were included. VEN+LDAC (SUCRA: 91.4%) and VEN+AZA (87.5%) were the highest ranked treatments for CR+CRi. VEN+LDAC was associated significantly higher response rates versus AZA (Odds Ratio: 5.64), LDAC (6.39), and BSC (23.28). VEN+AZA was also associated significantly higher response rates versus AZA (5.06), LDAC (5.74), and BSC (20.68). In terms of OS, VEN+AZA (SUCRA: 95.2%) and VEN+LDAC (75.9%) were the highest ranked treatments. VEN+AZA was associated with significant improvements in OS compared to AZA (hazard ratio: 0.66), LDAC (0.57) and BSC (0.37) and VEN+LDAC was associated with significant improvements in OS compared to LDAC (0.70) and BSC (0.46).VEN+AZA and VEN+LDAC demonstrated improved efficacy compared to alternative therapies among treatment naïve patients with AML ineligible for intensive chemotherapy.