Phase II trial of asciminib for newly diagnosed chronic myeloid leukemia.

Abstract

6589 Background: Asciminib is safe and effective across all lines of therapy of chronic myeloid leukemia (CML). Here, we report interim results from an investigator-initiated phase II trial of asciminib in patients (pts) with newly diagnosed (ND) CML. Methods: Asciminib was given at 80 mg/day in pts with ND CML in chronic phase or accelerated phase (clonal evolution only). The primary endpoint was the rate of major molecular response (MMR) by 12 months of therapy. AEs were recorded according to the CTCAE version 5.0 criteria. The data cutoff was January 20, 2026. Results: A total of 59 pts were treated with a median age at diagnosis of 49 years (range, 21-79); 33 (56%) were male. Sokal score was low in 29 pts (49%), intermediate in 21 (36%), and high in 9 (15%). With a median follow-up of 12 months, the cumulative best overall response was MCyR in 57 pts (97%), CCyR in 54 (92%), MMR in 40 (68%), MR4 in 21 (36%), and MR4.5 in 17 (29%). Among pts who completed at least 1 year of asciminib therapy, the MMR rate by 12 months was 71%. By 3 months, among 58 evaluable pts, 51 (88%) achieved MCyR or transcript levels below 10% on the international scale (IS), 42 (72%) CCyR or transcript levels below 1% IS, 16 (28%) MMR, 5 (9%) MR4, and 2 (3%) MR4.5. Seven pts (12%) had transcript levels above 10%. By 6 months, among 53 evaluable pts, the rate of CCyR was 85% (45/53), MMR 64% (34/53), MR4 34% (18/53), and MR4.5 26% (14/53). By 12 months, CCyR was achieved in 27 pts (87%), MMR in 22 (71%), MR4 in 13 (42%), and MR4.5 in 10 (32%). ASXL1 mutation was detected in 3 of 41 pts (7%) evaluated for cancer gene variants. Of them, two achieved a complete molecular response and one achieved CCyR as best response but later lost it with the acquisition of A337T and F497L mutations. The most frequent adverse events related or possibly related to asciminib included elevated lipase (Grade[G]2, n=9; G3, n=3; G4, n=1) and fatigue (G1, n=7; G2, n=2); 3 pts developed pancreatitis (G2, n=1; G3, n=2). A 71-year-old pt with a previous medical history of hypertension developed G5 acute coronary syndrome after 2.5 months of asciminib therapy. Overall, 8 of 59 pts (14%) discontinued asciminib due to: 1) adverse events in 4 (including 1 fatal acute coronary syndrome); 2) loss of CCyR in 2 (one with the emergence of A337T and F497L mutations and another with P465A and D381E mutations); 3) failure to achieve CCyR in 1 patient in the setting of cytopenias and asciminib dose reduction to 40 mg/day; and 4) withdrawal of consent by 1 patient due to inability to return to clinic for treatment due to social constraints and was in MR4 at the time of asciminib discontinuation. The 12-month rates of failure-free survival, event-free survival, transformation-free survival, and overall survival were 92%, 96%, and 98%, respectively. Conclusions: Treatment with asciminib in ND CML showed a MMR tare of 71% by 12 months of therapy with no new safety signals. Disease resistance was associated with the emergence of myristoyl pocket mutations. Clinical trial information: NCT06236724 .