Real-World Efficacy Profile of Compassionate Use of Asciminib in an Italian, Multi-Resistant Chronic-Phase Chronic Myeloid Leukemia (CML-CP) Patient Population

Abstract

Chronic myeloid leukemia (CML) patients who have experienced failure and/or intolerance to multiple lines of treatment have limited therapeutic possibilities. Asciminib is a first-in-class tyrosine kinase inhibitor (TKI) that inhibits the ABL Myristoyl Pocket (STAMP or Specifically Targeting the ABL Myristoyl Pocket) within the BCR::ABL1 oncoprotein. This retrospective Italian analysis reports the efficacy and safety outcomes of asciminib in treating 77 CML patients in chronic phase (CML-CP) within a compassionate use setting. Patients were heavily pretreated with a median of 3 TKIs (55.8% had prior ponatinib exposure). Overall, 57.1% and 42.9% patients switched to asciminib because of resistance and intolerance, respectively. Asciminib maintained or improved molecular responses (MRs) in most patients: as best response, 41 patients (53%) achieved a MR3 or better, with 25 patients (32.5%) reaching deep molecular response (DMR). Greater percentages of intolerant patients achieved MR compared with resistant patients, although the probability of reaching at least a MR3 was not significant between the two groups (p = 0.116). Patients with the T315I mutation responded to asciminib, while ponatinib pre-treated patients showed lower MR improvements compared to naïve patients and had a lower probability to reach a MR3 versus naïve patients (p = 0.0262). These results highlight asciminib remarkable tolerability and efficacy in real-world CML-CP patient population, including heavily pretreated patients, those intolerant and resistant to previous TKIs, and presenting several comorbidities. TRAIL REGISTRATION: The identification code for the MAP is CABL001AIT01M.

Keywords: TKI resistance/intolerance; asciminib; chronic myeloid leukemia in chronic phase (CML‐CP); major molecular response (MMR); real‐world; tyrosine kinase inhibitor (TKI).

FIGURE 1

(A) Percentage of patients achieving ≤ MR1, MR2, MR3, DMR during the treatment with asciminib. Radial charts showing the change in MR from baseline among patients who achieved an improved response at 3 months (B), as best response (C) and at last follow‐up (D).

FIGURE 2

MR distribution including discontinued patients at each timepoint. Data were recorded up to 18 months of asciminib treatment. “MR not reported” refers to patients with missing MR at the timepoint of interest and with asciminib exposure longer than timepoint of interest. Each discontinued patient is shown at the first timepoint in which they discontinued the treatment and they are excluded from treated patients at all the subsequent timepoints.

FIGURE 3

Percentage of resistant and intolerant patients achieving ≤ MR1, MR2, MR3, DMR during the treatment with asciminib. Data were recorded at 3 months, as best response and at last follow‐up. *One missing result was due to a MR value not available at baseline.

FIGURE 4

Kaplan‐Meier curve showing the event‐free survival of patients treated with asciminib. Dots represent censors. Patients at risk at each timepoint are those who are not censored and have yet to experience the event of interest.