Asciminib as monotherapy or adjunctive therapy for chronic myeloid leukaemia in blast phase

Abstract Introduction Asciminib, a first-in-class Specifically Targeting the ABL Myristoyl Pocket (STAMP) inhibitor, has emerged in recent years as a promising agent for the treatment of chronic myeloid leukemia (CML). Multiple studies have demonstrated its favourable efficacy and safety profile over ATP-competitive tyrosine kinase inhibitors (TKI). Asciminib is now approved for the treatment of CML in chronic phase (CML-CP) in different settings. However, CML in blast phase (CML-BP) remains challenging with a poor prognosis. Data on the use of asciminib in CML-BP are scarce. Here we report 7 cases of CML-BP managed at a tertiary hospital with asciminib. Methods Adult patients with CML-BP who received asciminib-based regimen (either as monotherapy or in combination with other agents) at Queen Mary Hospital, Hong Kong SAR, China, were retrospectively analysed. Details on patient demographics, clinico-pathologic characteristics, prior therapies, regimens of asciminib ± concurrent treatment, treatment outcomes, adverse events and death were collected. BCR::ABL1 transcript level was assessed with a minimum sensitivity of 10-4.5. Tyrosine kinase domain (KD) mutation analysis was performed using Sanger sequencing. Complete remission (CR) was defined as bone marrow blasts of ≤5% and resolution of all extramedullary disease. Molecular response was defined as ≥1 log reduction in BCR::ABL1 transcript level in patients in morphological CR. Overall response included achievement of CR and/or molecular response. Overall survival (OS) was defined as time from start of asciminib to death or last follow-up. Event-free survival (EFS) was defined as time from start of asciminib to treatment failure, relapse, death or last follow-up.Results Between July 2022 and June 2025, 7 patients (presenting as CML-BP, N=4; CML-CP progressing to BP, N=3) received asciminib-based treatment (male, N=4; female, N=3). The median age at asciminib treatment was 57 years (range, 29-65 years). Five patients (71%) had lymphoblastic crisis (B-lineage, N=4; T-lineage, N=1), and 2 patients had myeloblastic BP. Asciminib was used in third- or later-line of therapy. Six patients had previously received ponatinib, including one patient who had received asciminib while in CP after failing 4 TKIs. All patients had been tested for KD mutation, with two having at least 1 mutation, and both had F317L mutation. At the time of treatment, 3 patients had overt leukaemia, whereas 4 patients were converted back in CP after previous treatment for BP, but had molecular residual disease. Asciminib was used in conjunction with another ATP-binding TKI in 5 (71%) patients (ponatinib, N=4; dasatinib, N=1); three of whom also received additional treatment (venetoclax and hypomethylating agents, N=2; intensive chemotherapy, N=1). One patient received asciminib monotherapy. The median dosage of asciminib was 80 mg/day (range, 80-400 mg). For 3 patients with overt leukaemia, asciminib-based treatment resulted in CR in 2 patients, both of whom reached deep molecular response (MR4 and complete molecular response, respectively). For 4 patients in CP with residual disease, 3 patients (75%) achieved molecular response (MR3 or deeper, N=2; MR2, N=1). The overall response rate was 71%. At a median follow-up of 8 months, the 1-year OS was 66.7% with the median OS not reached. Median EFS was 10.6 months. Asciminib-based regimen was well tolerated, with only grade 1-2 non-haematological toxicities in 3 patients (hepatotoxicity, N=1; rash, N=1; myalgia, N=1) and grade 2 or above cytopenia in 3 patients.Conclusions The retrospective nature and small cohort size of our study notwithstanding, our analysis of this real-life cohort of CML-BP patients showed promising activity and reassuring safety profile of asciminib-based regimens. Patients experiencing ponatinib failure could potentially be salvaged by asciminib-based treatment.