Olverembatinib in accelerated-phase chronic myeloid leukemia: efficacy and safety evaluation.

We studied 130 consecutive subjects who presented with (N=29) or transformed to (N=101) accelerated-phase chronic myeloid leukemia (CML) and who received olverembatinib. Sixty-two were in second chronic phase. All failed ≥1 tyrosine kinase inhibitor (TKI) and 91 had BCR::ABL1T315I. Median follow-up was 28 months (interquartile range, 10-74 months). The 6-year cumulative incidences of major cytogenetic response (MCyR), complete cytogenetic response, major molecular response and molecular response 4.0 were 59% (95% confidence interval [CI]: 49- 69), 53% (95% CI: 42-62), 52% (95% CI: 41-62) and 42% (95% CI: 31- 53), respectively. The 6-year probabilities of transformation-free survival (TFS), CML-related survival and survival were 81% (95% CI: 72-90), 76% (95% CI: 67-87%) and 71% (95% CI: 61-82), respectively. In multi-variable analyses, an interval from diagnosis of CML to olverembatinib start <29 months, failure to achieve complete hematologic response on prior TKI therapy, hemoglobin concentration <98 g/L, blood and/or bone marrow blasts ≥8%, and/or high-risk additional chromosome abnormalities at the start of olverembatinib therapy, as well as not achieving early MCyR on olverembatinib correlated with worse outcomes. RUNX1 and STAT5A variants were significantly associated with worse TFS in the 82 subjects with targeted DNA-sequencing data. There were acceptable treatment-related adverse events. We conclude olverembatinib is effective and tolerable in subjects in accelerated-phase CML failing prior TKI therapy.