Asciminib Improves Efficacy vs Other Third-Line Treatments in Chronic Phase CML

Data revealed that a longer time to treatment discontinuation seen with asciminib favored its relative tolerability, correlating with the better-observed safety profile, according to data presented at the International Society for Pharmacoeconomics and Outcomes Research 2022

Asciminib (Scemblix) demonstrated improved efficacy compared with conventional third-line chronic-phase chronic myeloid leukemia (CML) treatments, according to data presented at the International Society for Pharmacoeconomics and Outcomes Research 2022 (iSPOR).

Findings were presented by Ehab Atallah, MD, professor of Medicine and section head of Hematological Malignancies at the Medical College of Wisconsin Division of Hematology and Oncology.

Data revealed that a longer time to treatment discontinuation (TTD) seen with asciminib favored its relative tolerability, correlating with the better-observed safety profile.

It is hard to compare third-line treatments for chronic phase CML due to absence of head-to-head studies as well as high heterogeneity which is often found in the baseline cohorts enrolled in single-arm studies, according to Atallah et al. Because of this, a matching-adjusted indirect comparison (MAIC) was put in place to compare some of the third-line chronic phase CML interventions available.

In this analysis, multiple MAICs were conducted to determine factors for asciminib vs comparators, including major molecular response (MMR), complete cytogenetic response (CcyR), and TTD). Method of moments was applied, and reweighting was done based on the propensity of enrollment in asciminib vs comparator trials.

Cross-trial differences were accounted for in comparisons by matching the defined baseline valuables available for the included studies, including sex, age, race, the partial cytogenetic response at baseline, mutation status, and ECOG performance status.

With a data cut-off of January 6, 202, and follow-up of 48 weeks or more, individual patient-level data from the ASCEMBL trial (NCT03106779) as well as study-level aggregate data of 5 studies was used for the analyses. All patients who were resistant or intolerant to previous tyrosine kinase inhibitors (TKIs), including ponatinib (AP24534; Iclusig), were analyzed.

In the open-label, randomized, phase 3 ASCEMBL trial, asciminib was examined in patients with chronic phase CML who were previously treated with 2 or fewer TKIs. Patients were randomized 2:1 to receive asciminib at a dose of 40 mg twice a day vs bosutinib 500 mg once a day. Randomization was stratified by major cytogenetic response (MCyR) status at baseline.

A total of 233 patients were randomized with 157 receiving asciminib and 76 receiving bosutinib. The median follow-up of the trial was 14.9 months. The primary end point of the trial was to compare the MMR rate at week 24 for asciminib compared with bosutinib, and the key secondary end point was to find the rate of MMR after 96 fIndings showed that at week 24, the MMR rate was 25.5% with asciminib vs 13.2% with bosutinib. After adjusting for MCyR, the difference in MMR rate between treatment arms was 12.2% (95% CI, 2.19-22.30; P = .029).

In terms of safety, fewer grade 3 or higher adverse events (AEs) (50.6% vs 60.5%) and AEs leading to treatment discontinuation (5.8% vs 21.1%) occurred in patients given asciminib vs those given bosutinib.

Overall, the ASCEMBL study demonstrated superior efficacy seen with asciminib vs that of bosutinib, as well as a favorable safety profile.

Findings presented at iSPOR used an estimated sample size which was calculated after matching the key baseline characteristics from the ASCEMBL trial and the other comparator studies examined. When compared to ponatinib (PACE: ≥ third-line cohort), there was a higher proportion of patients on asciminib who achieved MMR by 6 months (29% vs 19%) and 12 months (34% vs 23%). The cumulative MMR by 6 months with asciminib was also higher compared with dasatinib (Sprycel) (27% vs 21%).

Asciminib and ponatinib were similar regarding the PACE ≥ third-line cohort showing the CCyR by 6 months to be 38% vs 34%. At 12 months, the CCyR was 42% vs 43%. The proportion of patients achieving CCyR with asciminib were higher than nilotinib (Tasigna) and dasatinib (Sprycel) with 54% vs 15% by 6 months and 63% vs 31% by 12 months. When comparing TTD, patients remained on asciminib for a longer duration of time compared with nilotinib/dasatinib.

While methodology cannot account for all differences between studies and adjusts only for the reported baseline characters, asciminib showed to have improved and favorable efficacy results compared with conventional third-line chronic phase CML treatments. Asciminib also demonstrated longer TTD and a better safety profile.

Findings from this MAIC analysis can potentially help experts to make decisions and aid research in creating a treatment path for patients who fail 2 or more TKIs and who need effective and safe treatment options.

References:
Attalah EL, Maheshwari V, Mauro MJ, et al. A matching-adjusted indirect comparison of asciminib versus ponatinib, nilotinib and dasatinib in chronic phase chronic myeloid leukemia patients after ≥2 tyrosine kinase inhibitors. Presented at: 2022 International Society for Pharmacoeconomics and Outcomes Research; May 15-18, 2022. Washington, DC.
Réa D, Mauro MJ, Boquimpani C, et al. A phase 3, open-label, randomized study of asciminib, a STAMP inhibitor, vs bosutinib in CML after 2 or more prior TKIs. Blood. 2021;138(21):2031-2041. doi:10.1182/blood.2020009984