Clinical Summary:

• Design/Population: This phase 1 dose-escalation study evaluated olverembatinib plus blinatumomab in patients with relapsed/refractory Philadelphia chromosome–positive acute lymphoblastic leukemia or chronic myeloid leukemia in lymphoid blast phase.
• Key Outcomes: The combination achieved an objective response rate of approximately 91%, with more than 80% of patients attaining MRD negativity, while demonstrating a favorable safety profile and enabling subsequent consolidation with CAR T-cell therapy or allogeneic transplant.
• Clinical Relevance: These findings support olverembatinib plus blinatumomab as a promising chemotherapy-free strategy capable of inducing deep responses in heavily pretreated patients, including those with prior ponatinib exposure.

Elias Jabbour, MD, MD Anderson Cancer Center, Houston, Texas, discusses results from a phase 1 study evaluating olverembatinib in combination with blinatumomab in relapsed/refractory Philadelphia chromosome–positive acute lymphoblastic leukemia or chronic myeloid leukemia in lymphoid blast phase. 

The regimen produced high response rates and deep molecular remissions in a heavily pretreated population, including patients who had previously failed ponatinib and blinatumomab. Importantly, treatment was well tolerated, with no reported arterial occlusive events and no grade 3/4 cytokine release syndrome or immune effector cell–associated neurotoxicity syndrome.

These findings suggest that olverembatinib plus blinatumomab may represent a highly active chemotherapy-free platform capable of bridging patients to potentially curative consolidation strategies and support ongoing investigation in the frontline setting.

Transcript: 

My name is Elias Jabbour, Professor of Medicine in the department of leukemia at MD Anderson Cancer Center in Houston, Texas.

The combination of a TKI and immunotherapy, blinatumomab, or what we call a chemotherapy-free regimen, has proven to be effective in the management of Philadelphia chromosome–positive ALL. We previously reported on the combination of blinatumomab and ponatinib, with excellent outcomes, including a 4-year survival of 90%, which is amazing.

Now, olverembatinib is a very potent TKI that is effective in patients with ponatinib resistance, and it can overcome compound mutations causing resistance to ponatinib. Therefore, based on this evidence, we decided to combine olverembatinib and blinatumomab in patients with CML lymphoid blast phase and relapsed/refractory Philadelphia chromosome–positive ALL.

The study was a phase 1, 3+3 dose-escalation design. We evaluated olverembatinib at 30 mg every other day and 40 mg every other day in an escalation fashion. The DLT period was 6 weeks, and patients received up to 5 cycles of blinatumomab in combination. After that, patients could receive maintenance with olverembatinib or proceed to CAR T-cell therapy or transplant. We have enrolled 13 patients so far. These patients had failed multiple prior therapies. About half had failed ponatinib, and many had also failed blinatumomab.

The T315I mutation was reported in about 20% of patients, and around 40% had what we call cardiovascular risk factors, including hypertension, dyslipidemia, or others. Therefore, this was a heavily pretreated, high-risk patient population, making both efficacy and safety particularly important.

From a safety point of view, the treatment was well tolerated. Essentially, what we saw were neutropenia and thrombocytopenia early on, but nothing significant. Importantly, we did not observe arterial occlusive events, which are known side effects of ponatinib. We also did not report any grade 3/4 ICANS or CRS. Therefore, the regimen was well tolerated.

When it comes to efficacy, the overall response rate was around 91%, which is very encouraging. We measured MRD, and more than 80% of patients achieved MRD negativity by RT-PCR or flow cytometry. The median follow-up is around 18 weeks, so relatively short. We currently have five patients who continue to respond and are doing well.

In addition, 3 patients went on to receive CAR T-cell therapy as consolidation, and 2 patients proceeded to transplant. This is very important because the regimen allowed patients to bridge to more definitive therapies. What we have seen is that responses occur early, some are very durable, and some have enabled patients to receive further consolidation.

Based on these observations, I can say that the combination of blinatumomab and olverembatinib appears very safe, with no major adverse events observed. It induces deep and durable responses and enables patients to receive consolidation strategies such as CAR T-cell therapy or transplant. These findings warrant further investigation in the frontline setting. 

Today, olverembatinib is being tested in the frontline setting in combination with immunotherapy and in randomized trials versus standard-of-care TKI-based approaches.

Source: 

Jabbour E, Baer MR, Hunter A, et al. Olverembatinib (HQP1351) combined with blinatumomab in patients with lymphoid blast phase chronic myeloid leukemia (CML-LBP) or Philadelphia chromosome–positive B-cell precursor acute lymphoblastic leukemia (Ph+ BCP-ALL). Presented at the ASCO Annual Meeting. May 29 - June 2, 2026. Chicago, Illinois. Abstract 6513.