Highlights in chronic myeloid leukaemia (CML)

Dr Adriano Salaroli, a haematologist at the Institut Jules Bordet in Brussels, discussed new data on CML. 

First of all, he focused on the ASC4FIRST study’s 96-week findings. This trial explored asciminib as a first-line treatment following its established efficacy and safety in third-line settings. The study randomised 405 patients to receive either asciminib or investigator-selected TKIs, with the primary endpoint being the MMR rate at 48 weeks across different comparator groups, including imatinib and second-generation TKIs. At 96 weeks, asciminib demonstrated superior response rates across all strata, including deep molecular responses, compared to the investigator-selected TKIs. Moreover, the safety profile favoured asciminib, showing fewer grade 3 adverse events, treatment discontinuations and dose adjustments. These results underscore the favourable benefit-risk profile of asciminib, strongly supporting its use as first-line therapy for patients with CML-CP.

The interim analysis of the ASC2ESCALATE trial evaluates asciminib in the second-line setting and its potential role in dose escalation for CML-CP patients with BCR::ABL levels >1% at week 24. The trial enrolled 71 patients, with 47% previously treated with dasatinib and 36% with imatinib. Patients transitioned to asciminib due to either lack of efficacy or intolerance. By week 24, 86% of patients achieved BCR::ABL levels <1%, with only two requiring dose escalation to 200 mg QD. The safety profile of asciminib remained consistent with its established safety data, with no new or worsening safety concerns observed during the study. These findings confirm asciminib’s efficacy and favourable safety profile in the second-line setting. The potential benefit of dose escalation in patients with suboptimal molecular responses remains to be established.

Patients with CML-CP often exhibit poor outcomes in the second-line setting, particularly those with refractory disease following second-generation TKIs. Olverembatinib, a third-generation TKI with proven efficacy in the third line and in T315I-mutated patients, was evaluated for efficacy and safety in second-line treatment in 43 non-T315I-mutated patients. The primary endpoint was CCYR. Among these patients, 28% had received imatinib as first-line therapy, while 72% had received second-generation TKIs (nilotinib 25%, flumatinib 33%, dasatinib 14%). Notably, 93% were resistant to first-line treatment, representing an aggressive disease subgroup. CCYR was achieved in 74% of patients, and MMR in 41%. Interestingly, both CCYR and MMR rates were higher in patients treated with second-generation TKIs in the first line compared to imatinib and in those with BCR::ABL mutations compared to those without. The safety profile, primarily haematologic toxicity and skin hyperpigmentation, was consistent with previous reports. These findings support olverembatinib’s use in second-line CP-CML, particularly in patients failing second-generation TKI frontline therapy.