https://orcid.org/0000-0003-1281-3802
Key Points
Asciminib is an effective salvage option in patients with relapse / refractory Philadelphia chromosome-positive acute leukemias.
New mutations of resistance may occur that warrant further investigations
Asciminib (ASC) is an allosteric inhibitor of BCR::ABL1 that binds the myristoylation site of the ABL1 protein. We report the use of ASC in relapsed Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) and lymphoid blast crisis of chronic myeloid leukemia (LBC-CML) in 41 patients retrospectively collected in France. Median age was 56 years (range: 19-84). Most patients (78%) received ASC as a third-line or later treatment, with 93% previously treated with ponatinib. Twenty-seven out of 35 analyzed patients had BCR::ABL1 mutations, including T315I (n=18) or compound mutations (n=8). ASC was prescribed at 200 mg BID in 83% of the patients, alone (n=20) or in combination (n=21). Overall, 30/36 evaluable patients achieved a composite complete response (CR/CRi), including measurable residual disease negativity (defined by BCR::ABL1/ABL1 <0.01% in bone marrow) in 13/23 patients (57%). The median overall survival and event-free survival (EFS) were 9.8 and 4.9 months respectively. EFS was improved when ASC was administered in combination rather than as monotherapy (7.93 vs 4.23 months). Post-ASC mutations were analyzed in 7 relapsing patients, identifying a new Q252H mutation in 2 cases. In conclusion, our findings suggest that ASC is an effective salvage therapy for Ph+ ALL and LBC-CML.
