Phase 1b trial reports promising outcomes with olverembatinib plus blinatumomab in relapsed or refractory CML or ALL

TKIs + blinatumomab represents a chemotherapy‑free regimen in Ph+ ALL associated with high survival. Olverembatinib + blinatumomab resulted in favorable and deep responses in patients with CML‑LBP and Ph+ BCP‑ALL. This treatment strategy was a successful bridge to CAR-T and transplantation in several patients. The combination had a manageable safety profile, with no new safety signals. Further evaluation of this combination is warranted. — Elias Jabbour, MD

Olverembatinib, a third-generation BCR::ABL1 tyrosine kinase inhibitor, plus blinatumomab demonstrated promising efficacy and manageable safety for patients with relapsed or refractory Philadelphia chromosome–positive lymphoid blast phase chronic myeloid leukemia (CML-LBP) or B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in a phase 1b study.

The study, led by Elias Jabbour, MD, of the University of Texas MD Anderson Cancer Center in Houston, was presented at the Fourteenth Annual Meeting of the Society of Hematologic Oncology in Houston, Texas.

The trial enrolled eight patients with BCP-ALL and one with CML-LBP between January 2023 and June 2025. Seven patients were BCR::ABL1 p190–positive and two were p210–positive, and one patient had T315I mutation. Six patients previously received blinatumomab.

All patients received olverembatinib at 30 mg every other day with planned escalation to 40 mg every other day alongside standard blinatumomab in six-week cycles. The presentation covered dose-limiting toxicities in cycle one, as well as safety, tolerability, complete response (CR) rate, and measurable residual disease (MRD)–negativity rate.

Grade 3 treatment-related adverse events included increased lipase, neutropenia, thrombocytopenia, and pancreatitis in one patient each. No dose-limiting toxicities occurred with the 30 mg dose. One patient on the 40 mg dose developed grade 3 pancreatitis that resolved with supportive care and dose reduction to 30 mg. This patient achieved a CR and negative MRD by the end of cycle one, according to the report.

Over a median treatment duration of 15.7 weeks (range, 1.4-37.1), one patient discontinued due to disease progression and three discontinued to proceed to transplantation or chimeric antigen receptor T-cell therapy. Among five patients with positive MRD and no CR at baseline, four achieved CR and two achieved MRD negativity. One patient died due to disease progression unrelated to olverembatinib plus blinatumomab.

Ultimately, olverembatinib plus blinatumomab provided “encouraging response rates and MRD clearance,” and was generally well tolerated. These phase 1b data “support further investigation of this chemotherapy-free approach,” Dr. Jabbour and colleagues wrote.

Reference
Jabbour E, Baer MR, Hunter AM, et al. Olverembatinib combined with blinatumomab in patients with lymphoid blast phase chronic myeloid leukemia or Philadelphia chromosome–positive B-cell precursor acute lymphoblastic leukemia. Abstract ALL-589. Presented at the 2026 Society of Hematologic Oncology Annual Meeting; September 9-12, 2026; Houston.

Read more from SOHO 2026 here.