Ponatinib plus blinatumomab demonstrated promising results as treatment of Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), according to updated results from a phase 2 trial presented at the Annual Meeting of the Society of Hematologic Oncology (SOHO).

“Based on these very highly favorable outcomes, particularly in the frontline setting, we can say that this combination of ponatinib and blinatumomab may serve as a very promising chemotherapy-free and a stem cell transplant–sparing regimen for patients with Ph+ ALL,” said Fadi G. Haddad, MD, of The University of  Texas MD Anderson Cancer Center, during the study presentation.

The current standard of care for the treatment of Ph+ ALL is chemotherapy plus a tyrosine kinase inhibitor (TKI); however, the majority of patients relapse due to a T315I mutation. The aim of this study was to evaluate the combination of ponatinib, a pan-BCR-ABL1 TKI, with blinatumomab for adult patients with Ph+ ALL.

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The phase 2 trial treated 40 patients with newly diagnosed, 14 with relapsed/refractory Ph+ ALL, and 6 patients with lymphoid-accelerated or blast-phase chronic myeloid leukemia (CML-LBP) to receive ponatinib plus blinatumomab. Patients were treated in a 6-week induction phase, which included 30 mg of ponatinib for 6 weeks and blinatumomab for 4 weeks. This was followed by a consolidation phase with 4 cycles of a lower dose of ponatinib at 15 mg plus blinatumomab. Intrathecal methotrexate with cytarabine were also administered during the induction and consolidation phases. A maintenance phase included 15 mg of ponatinib for 5 years.

The overall rate of complete response/complete response with incomplete count recovery (CR/CRi) was 94%, including 96% among patients with newly-diagnosed ALL, 92% with relapsed/refractory ALL, and 83% with CML-LBP. The median duration of CR was 15 months.

Complete molecular response (CMR) was achieved by 79% of patients overall, including 87% of patients with newly-diagnosed ALL and 79% of patients with relapsed/refractory disease. The CMR rate was 33% among patients with CML-LBP.

Among patients with newly-diagnosed Ph+ ALL, 37 continue to have an ongoing response and did not undergo hematopoietic stem cell transplant (HSCT). There was 1 patient who continued to have a response after HSCT, and 2 patients died.

“Only 1 patient in the frontline setting was transplanted due to detectable BCR-ABL transcript levels,” Dr Haddad noted.

In the relapsed/refractory Ph+ ALL cohort, 6 patients underwent HSCT and 2 patients continued to have a response and did not undergo HSCT. There were 4 patients who had achieved CR/CRi who relapsed and 1 who died. There was 1 patient who did not respond to treatment.

Among all patients with Ph+ ALL, the event-free survival (EFS) and overall survival (OS) were not reached. In the relapsed/refractory group, the median EFS was 15 months and OS was not reached. The median EFS and OS among patients with CML-LBP was 8 and 17 months, respectively.

Dr Haddad concluded that “based on the results that we have, we have seen that this combination of ponatinib and blinatumomab is safe and effective.”


Haddad FG, Kantarjian HM, Short NJ, et al. Updated results from the phase II study of blinatumomab in combination with ponatinib in Philadelphia chromosome–positive acute lymphoblastic leukemia. Presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 28-October 1, 2022. Abstract ALL-424.