Olverembatinib Well-Tolerated in Adults With TKI-Resistant Chronic Myeloid Leukemia

Olverembatinib was well-tolerated, with significant anti-leukemic activity in adults with tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia (CML) in the chronic phase (CML-CP) and accelerated phase (CML-AP), especially in those patients with the T315I mutation, according to results of a phase 1/2 study.

“Olverembatinib is a new potent BCR-ABL1 TKI with preclinical activity against T315I-mutated CML,” stated Qian Jiang, National Clinical Research Center for Hematologic Disease, Peking University Institute of Hematology, Beijing, China, and colleagues. “BCR-ABL1^T315I mutations confer resistance to tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia.”

Phase 1 of the study investigated different doses of oral olverembatinib, from 1mg to 60mg in 11 cohorts, administered once every other day in 28 day cycles. The maximum tolerated dose, recommended phase 2 dose of 40 mg every other day, safety, efficacy, and pharmacokinetics of olverembatinib were evaluated at this stage. In phase 2 of the study, 40 mg olverembatinib was administered orally on alternate days for 28-day cycles. The primary outcome was major cytogenetic response (MCyR) and major hematologic response by the end of Cycle 12 in CML-CP and CML-AP, respectively.

A total of 165 patients (>80.0% of whom had received ≥2 TKIs) were enrolled in this study. Among 127 patients with CML-CP, the 3-year cumulative incidences of achieving MCyR, complete cytogenetic response (CCyR), major molecular response (MMR), MR^4.0, and MR^4.5 were 79.0, 69.0, 56.0, 44.0 and 39.0%, respectively. The highest response rates were observed in patients with a single T315I mutation. Among 38 patients with CML-AP, the 3-year cumulative incidences of achieving MCyR, CCyR, MMR, MR^4.0, and MR^4.5 were 47.4%, 47.4%, 44.7%, 39.3%, and 32.1%, respectively. In multivariate analyses, baseline BCR-ABL1 mutation status was significantly associated with cytogenetic and molecular responses.

The most common treatment-related adverse events included skin hyperpigmentation, hypertriglyceridemia, proteinuria, and severe thrombocytopenia.

Dr Jiang and colleaguers concluded, “Olverembatinib was well tolerated, with significant antileukemic activity in adults with TKI-resistant CML-CP and CML-AP, especially those with the T315I mutation.”

Source:

Jiang Q, Li Z, Qin Y, et al. Olverembatinib (HQP1351), a well-tolerated and effective tyrosine kinase inhibitor for patients with T315I-mutated chronic myeloid leukemia: results of an open-label, multicenter phase 1/2 trial. J Hematol & Oncol. 2022;15(1). doi:10.1186/s13045-022-01334-z