Dr Hughes on the Safety of Asciminib in Ph+ CP-CML

Timothy Hughes, MD, MBBS, FRACP, FRCPA, clinical director, Precision Cancer Medicine Theme at SAHMRI, consultant hematologist, Royal Adelaide Hospital, discusses safety data from the phase 3 ASC4FIRST trial (NCT04971226) evaluating asciminib (Scemblix) vs investigator-selected TKIs in patients with newly diagnosed, Philadelphia chromosome (Ph)–positive, chronic-phase chronic myeloid leukemia (CP-CML).

Findings presented at the 2024 ASCO Annual Meeting showed that the study met its co-primary end points. At week 48, asciminib (n = 201) produced a major molecular response (MMR) rate of 67.7% vs 49.0% investigator-selected TKIs (n = 204; difference, 18.9%; 95% CI, 9.6%-28.2%; P < .001). For patients treated with asciminib (n = 101) or an investigator-selected TKI (n = 102) within the imatinib stratum, the MMR rates at week 48 were 69.3% and 40.2%, respectively (difference, 29.6%; 95% CI, 16.9%-42.2%; P < .001).

The MMR rate at week 48 for second-generation asciminib (n = 100) or a second-generation TKI (n = 102) was a key secondary end point. The MMR rate at week 48 was 66.0% for asciminib and 57.8% for second-generation TKIs (difference, 8.2%; 95% CI, –5.1% to 21.5%).

Regarding safety, Hughes explains that a significant unmet need exists around the use of second or third-generation TKIs in patients with Ph+ CP-CML. Efficacy benefits of other agents in this class have historically been diminished by associated toxicities, he says. Hughes notes that during ASC4FIRST, asciminib exhibited a high potency with a toxicity profile that is as good or better than that of imatinib (Gleevec). Given the efficacy and safety data derived for asciminib, this could represent a beneficial treatment that does not feature the same level of safety concerns observed for other second- or third-generations TKIs, he says.