Olverembatinib produced progressively deepening cytogenetic and molecular responses in second-line chronic-phase chronic myeloid leukemia.
Olverembatinib (HQP1351) given as second-line therapy led to responses that deepened over time in patients with chronic-phase chronic myeloid leukemia (CP-CML), according to updated data from a single-arm, multicenter study (ChiCTR2200061655) presented at the
Data from the trial showed that as of January 14, 2026, patients with CP-CML who received olverembatinib monotherapy (n = 42) achieved a complete cytogenetic response (CCyR) rate of 76.2% and a major molecular response (MMR) rate of 47.6%. Complete hematologic response (CHR) was achieved by 83.3% of patients, and 82.1% of patients achieved a major cytogenetic response (MCyR).
Additionally, responses deepened with longer follow-up. The end-of-cycle CCyR and MMR rates rose from 57.5% and 25.0%, respectively, at cycle 6 to 91.3% and 60.9%, respectively, at cycle 24, respectively.
“Overall, with longer treatment duration, olverembatinib not only helped patients achieve deeper responses, but also continued to provide durable clinical benefit while maintaining a favorable safety and tolerability profile,” lead study author, Weiming Li, MD, stated in a news release.²
Li is a professor in the Institute of Hematology at Wuhan Union Hospital and Tongji Medical College at Huazhong University of Science and Technology in China. He is also the principle investigator of the study.
The open-label study enrolled adults with CP-CML who were resistant or intolerant to first-line TKI therapy and did not harbor T315I mutations.1 Patients also needed to have an ECOG performance status of 2 or lower, in addition to adequate liver and renal function.
Patients received oral 40-mg doses of olverembatinib every other day in 28-day cycles, with their cytogenetic responses, molecular responses, and safety assessed every 3 cycles. The primary end point of the trial was CCyR rate.
Baseline characteristics for all enrolled patients (n = 47) revealed that the median age was 42.0 years (range, 19-70), with most patients being male (66%) and having an ECOG performance status of 0 (95.7%). First-line treatments for patients broke down as imatinib (Gleevec; 25.5%), nilotinib (Tasigna; 27.7%), flumatinib (Hansoh Xinfu; 31.9%), and dasatinib (Sprycel; 14.9%); 93.6% of patients were resistant and 6.4% of patients were intolerant to their first-line treatment. No mutation was detected in 76.6% of patients, whereas 14.9%, 4.3%, and 4.3% of patients harbored 1, 2, or 3 mutations, respectively. The median time from diagnosis to the start of olverembatinib treatment was 1.03 years (range, 0.3-21.1), with 7.0%, 4.7%, 2.3%, and 11.6% of patients discontinuing olverembatinib treatment due to adverse effects (AEs), treatment progression, disease progression, and other reasons, respectively.
Among patients who had received a second-generation TKI for their first-line treatment (n = 32), 81.3% achieved a CCyR, and 50.0% achieved an MMR. Among the patients who had previously received imatinib (n = 10), 60.0% achieved a CCyR, and 40.0% achieved an MMR. Patients with baseline BCR::ABL1 International Scale (IS) levels below 10% (n = 9) achieved a CCyR rate of 100.0% and an MMR rate of 77.8%, compared with respective rates of 69.7% and 39.4% among patients with baseline BCR::ABL1 IS levels of 10% or higher (n = 33).
Among safety-evaluable patients (n = 47), 89.4% experienced any-grade treatment-related AEs (TRAEs), 44.7% experienced grade 3 or higher TRAEs, and 12.8% had serious AEs.
Common any-grade TRAEs included decreased platelet counts (59.6%), skin hyperpigmentation (55.3%), decreased neutrophil counts (34.0%), decreased white blood cell (WBC) counts (31.9%), anemia (36.2%), hyperuricemia (31.9%), and increased creatine phosphokinase levels (27.7%). Common grade 3 or higher TRAEs included decreased platelet counts (42.6%), decreased neutrophil counts (25.5%), decreased WBC counts (21.3%) and anemia (8.5%). Serious AEs included decreased platelet counts (6.4%) and anemia, myelosuppression, and pyrexia (2.1% each); no deaths were reported.
Two cardiovascular events, both of which were grade 1 hypertension, were considered possibly related to treatment.
“These findings further support [olverembatinib’s] role as a potential second-line treatment option for patients with CP-CML without the T315I mutation and provide stronger evidence for clinical practice,” Li added in the news release.2 “We also look forward to additional long-term follow-up data to further validate its efficacy and safety, and to provide stronger evidence-based support for the standardized use and guideline recommendations of olverembatinib in the second-line treatment setting, helping to deliver more optimized treatment options for patients and clinicians.”
