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POSC35 Venetoclax Combination Therapies Show Significant Improvements in Overall Survival and Remission in Treatment-Naïve Patients with AML Who Are Ineligible for Intensive Chemotherapy: A Network Meta-Analysis

      Objectives

      The aim of this network meta-analysis (NMA) was to assess the relative efficacy of venetoclax (VEN) plus azacitidine (AZA) and VEN plus low-dose cytarabine (LDAC) versus AZA, LDAC, decitabine, and best supportive care (BSC) only for adult patients with untreated acute myeloid leukemia (AML) deemed ineligible for intensive chemotherapy.

      Methods

      A systematic literature review was conducted in October 2020 to identify Phase 3, randomized, controlled trials in the target population. Overall survival (OS) and complete remission + complete remission with incomplete blood count recovery (CR+CRi) were extracted from identified trials and were compared using a Bayesian fixed-effects NMA. Treatment ranking was based on surface under cumulative ranking curve (SUCRA) with higher value indicating higher likelihood of being in the top rank.

      Results

      Five trials (VIALE-A, VIALE-C, AZA-001, AZA-AML-001, and DACO-016) were included in the NMA. VEN+AZA and VEN+LDAC were the highest ranked treatments for OS (SUCRA: 95.2% and 75.9%, respectively) followed by decitabine (56.4%), AZA (47.7%), LDAC (22.6%), and BSC (0.8%). VEN+AZA was associated with significant improvements in OS compared to AZA (HR: 0.66), LDAC (HR: 0.57) and BSC (HR: 0.37). VEN+LDAC was associated with significant improvements in OS compared to LDAC (HR: 0.70) and BSC (HR: 0.46). VEN+AZA and VEN+LDAC were also the highest ranked treatments for CR+CRi (SUCRA: 87.5% and 91.4%, respectively) followed by decitabine (61.4%), AZA (33.8%), LDAC (25.8%), and BSC (0.4%). VEN+AZA and VEN+LDAC were associated with significant improvements in CR+CRi compared to AZA (OR: 5.06 for VEN+AZA; 5.64 for VEN+LDAC), LDAC (OR: 5.74; 6.39) and BSC (OR: 20.68; 23.28), respectively.

      Conclusions

      Results of this NMA indicate that VEN+AZA and VEN+LDAC combinations are associated with significantly higher CR+CRi rates and prolonged OS compared to alternative treatments. These combinations are efficacious options for treatment-naïve patients with AML who are ineligible for intensive chemotherapy.