OBJECTIVES: Comparative analysis of third line (3L) chronic phase chronic myeloid leukemia (CP-CML) treatments is challenging due to absence of head-to-head studies and high heterogeneity in baseline cohorts of single-arm studies. As standard calculations of relative efficacy are unfeasible, a matching-adjusted indirect comparison (MAIC) was opted to compare the 3L CP-CML interventions.

METHODS: Multiple MAICs were conducted to analyze major molecular response (MMR), complete cytogenetic response (CCyR) and time to treatment discontinuation (TTD) for asciminib vs comparators. Method of moments was applied and reweighting was done based on propensity of enrollment in asciminib vs comparator trials. Individual patient-level data from ASCEMBL (data-cut Jan 6, 2021; follow-up ≥48 weeks) and study-level aggregate data of comparators (five studies) was used for the analyses. Conservatively, all patients resistant or intolerant to previous tyrosine kinase inhibitors, including ponatinib, were analyzed excluding patients with CCyR at baseline.

RESULTS: Compared to ponatinib (PACE: ≥3L cohort), a higher proportion of patients on asciminib achieved MMR (by 6-months: 29% vs 19% [OR 1.78]; 12-months: 34% vs 23% [OR 1.74]). By 6-months, cumulative MMR with asciminib was higher versus dasatinib (Tan, 2019) (27% vs 21% [OR 1.40]). Asciminib was similar to ponatinib (PACE: ≥3L cohort) in achieving CCyR (by 6-months: 38% vs 34% [OR 1.18]; 12-months: 42% vs 43% [OR 0.94]). Proportion of patients achieving CCyR with asciminib were higher than nilotinib/dasatinib (Ibrahim, 2010) (by 6-months: 54% vs 15% [OR 6.63]; 12-months: 63% vs 31% [OR 3.75]). On comparing TTD, patients remained on asciminib for a longer duration vs nilotinib/dasatinib.

CONCLUSION: Although the methodology cannot account for all between-study differences and adjusts only for the reported baseline characters, asciminib exhibited an improved efficacy vs conventional 3L CP-CML treatments. Furthermore, a longer TTD with asciminib favors its relative tolerability aligning with the clinically observed better safety profile.