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Olverembatinib can improve outcomes when compared to best available therapy (BAT) in patients with tyrosine kinase inhibitor (TKI)-resistant chronic phase chronic myeloid leukemia (CML), according to research presented at the ASH Annual Meeting 2023.
Researchers found that olverembatinib improved responses and event-free survival (EFS) but not progression-free survival (PFS) or overall survival (OS) in a phase 2 trial.
However, these results were impacted by the high rate of crossover from the BAT arm to the olverembatinib arm.
This trial (ClinicalTrials.gov Identifier: NCT04126681) enrolled 144 patients with chronic phase CML whose disease was resistant or intolerant to imatinib, dasatinib, or nilotinib.
The patients were randomly assigned to the olverembatinib arm (n=96) or the BAT arm (n=48). Baseline characteristics were similar between the arms. In the olverembatinib arm, 35.4% of patients had a complete hematologic response (CHR) at baseline, and 11.5% had a partial cytogenetic response (PCyR). In the BAT arm, 37.5% of patients had a CHR, and 10.4% had a PCyR.
Olverembatinib was given at 40 mg every other day. BAT included nilotinib (n=22), dasatinib (n=16), imatinib (n=2), nilotinib and hydroxyurea (n=2), dasatinib and interferon (n=2), nilotinib and interferon (n=1), and interferon plus hydroxyurea and homoharringtonine (n=1).
Most patients in the BAT arm — 35 of 48 — crossed over to receive olverembatinib. The median treatment duration was 21 months in the olverembatinib arm and 3 months in the BAT arm.
The median follow-up was 31 months in the olverembatinib arm and 30 months in the BAT arm. Forty patients in the olverembatinib arm and 6 in the BAT arm were still on their assigned treatment at last follow-up.
Responses were superior with olverembatinib. At 36 months, the cumulative incidence of major cytogenetic response (MCyR) was 48% in the olverembatinib arm, 30% in the BAT arm, and 43% in patients who switched to olverembatinib from BAT. The cumulative incidence of complete cytogenetic response (CCyR) was 37%, 16%, and 30%, respectively.
The cumulative incidence of major molecular response (MMR) was 27% in the olverembatinib arm, 10% in the BAT arm, and 24% in patients who switched to olverembatinib from BAT. The cumulative incidence of molecular response 4.0 was 24%, 3%, and 22%, respectively.
There was a significant improvement in EFS with olverembatinib (hazard ratio [HR], 0.4; 95% CI, 0.3-0.5; P <.0001) but no significant difference in PFS (HR, 0.9; 95% CI, 0.2-3.4; P =.884) or OS (HR, 0.6; 95% CI, 0.2-2.2; P =.418) between the olverembatinib and BAT arms.
In the olverembatinib arm, the EFS rates were 59% at 12 months, 47% at 24 months, and 47% at 36 months. The PFS rates were 92% at 12 months, 89% at 24 months, and 89% at 36 months. The OS rates were 97% at 12 months, 94% at 24 months, and 94% at 36 months. EFS, PFS, and OS rates for the BAT arm were not presented.
The most common treatment-related adverse events in the olverembatinib arm were anemia, leukopenia, thrombocytopenia, neutropenia, skin pigmentation, and creatinine phosphokinase elevation. There were 7 treatment-related arterial occlusive events in 5 patients in the olverembatinib arm.
The most common treatment-related adverse events in the BAT arm were anemia, leukopenia, thrombocytopenia, neutropenia, and hyperbilirubinemia.
Disclosures: This research was supported by Ascentage Pharma Group Inc. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the reference for a full list of disclosures.
Reference
Jiang Q, Li Z, Zhang G, et al. Olverembatinib (HQP1351) demonstrates efficacy vs. best available therapy (BAT) in patients (pts) with tyrosine kinase inhibitor (TKI)-resistant chronic myeloid leukemia chronic-phase (CML-CP) in a registrational randomized phase 2 study. Presented at ASH 2023. December 9-12, 2023. San Diego, CA. Abstract 869.
This article originally appeared on Cancer Therapy Advisor
