Olverembatinib may offer a safe and effective second-line treatment option for patients with chronic-phase chronic myeloid leukemia (CP-CML), particularly those who have not responded well to first-line second-generation tyrosine kinase inhibitors (TKIs). These findings from the ChiCTR2200061655 study were presented at the 2024 ASH Annual Meeting & Exposition.
Dr. Li Weiming, from the Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, highlighted the significance of the research: "This is the first report of olverembatinib as a second-line TKI therapy in patients with CML. Olverembatinib demonstrated remarkable efficacy in patients with CP-CML, without T315I mutations who [were] resistant or intolerant to prior first-line TKI treatment."
The study aimed to evaluate olverembatinib as a second-line treatment for patients without the T315I mutation, given that third-generation BCR-ABL1 TKIs have already shown efficacy in patients resistant or intolerant to two prior TKIs or those with the T315I mutation.
The trial enrolled 43 patients with CP-CML, with 93.9% being first-line TKI-resistant and 6.9% being first-line TKI-intolerant. The median age of participants was 45 years (range: 19-70), and 69.8% were male.
Efficacy Outcomes
As of the data cutoff on November 15, 2024, efficacy was assessed in 33 patients. At a median follow-up of 16 months (range: 2-18), 74.1% (20 of 27 patients) achieved complete cytogenetic response (CCyR), and 40.6% (13 of 32 patients) experienced major molecular response (MMR).
An analysis of the data showed that CCyR and MMR rates improved over time: Cycle 6 (53.4% and 28.6%), Cycle 9 (64.8% and 32.5%), Cycle 12 (69.1% and 32.5%), and Cycle 18 (77.7% and 43.9%).
Among the 33 efficacy-evaluable patients, 24 had been pretreated with a second-generation TKI as their first-line treatment, with 78.9% achieving CCyR and 43.5% achieving MMR. For the 9 patients pretreated with imatinib, 50% achieved CCyR and 33.3% achieved MMR.
Patients with less than 10% BCR-ABL International Scale (8 patients) achieved CCyR in all cases and MMR in half of the cases, while those with greater than 10% (25 patients) achieved CCyR in 69.6% of cases and MMR in 37.5% of cases.
In patients without mutations (24 patients), 65.0% achieved CCyR and 34.8% achieved MMR, while among patients with mutations (9 patients), 85.7% achieved CCyR and 55.6% achieved MMR.
Safety Profile
In the safety population of 43 patients, 6 patients (14.0%) experienced treatment-related serious adverse events, including 3 patients (7%) with decreased platelet counts. No deaths were reported.
Trial Details
Key eligibility criteria included an ECOG performance score of 0 to 2, adequate liver and renal function, and a life expectancy of at least three months. Patients received 40 mg of olverembatinib orally every other day in 28-day cycles. Cytogenetic response, molecular response, and safety profile were evaluated every 3 cycles.
Prior first-line treatments included imatinib (Gleevec) in 12 patients (28.6%) and second-generation TKIs in 30 patients (71.4%), specifically dasatinib (Sprycel, 3 patients, 12.5%), nilotinib (Tasigna, 11 patients, 45.8%), or flumatinib (10 patients, 41.7%).
No mutation was found in 32 of 43 patients (74.4%), and 11 patients (25.7%) had mutations other than T315I at baseline.
As of the data cutoff date, 11 patients (25.6%) discontinued treatment due to adverse events (3 patients, 7%), treatment failure (2 patients, 4.7%), and disease progression (1 patient, 2.3%).
