High Complete Molecular Response Rates with Ponatinib Plus Blinatumomab in Ph+ ALL

By Cecilia Brown - January 31, 2023

A chemotherapy-free regimen with simultaneous ponatinib and blinatumomab led to high complete molecular response rates in patients with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), according to results from a phase II study.

Elias Jabbour, MD, of the MD Anderson Cancer Center, and colleagues conducted the study and published its results in The Lancet Haematology.

Dr. Jabbour and colleagues conducted a single-center, single-arm phase II study that included adults with newly diagnosed, relapsed, or refractory Ph+ acute lymphoblastic leukemia ALL. The chemotherapy-free regimen was shown to be in newly diagnosed patients, according to a subgroup analysis of the trial presented during the 2022 American Society of Hematology Annual Meeting and Exhibition.

Of 72 patients assessed between February 6, 2018, and May 6, 2022, 60 (83%) enrolled and received the combination therapy. Most patients who enrolled and received therapy had newly diagnosed Ph+ ALL (67%), while 23% had relapsed or refractory Ph+ ALL, and 10% had chronic myeloid leukemia (CML) in lymphoid blast phase. The median patient age was 51 years, 85% of patients were White or Hispanic, and 53% were men. The median follow-up duration was 16 months.

Patients received ponatinib 30 mg orally plus continuous intravenous blinatumomab 28 μg over 24 hours for 28 days each cycle for up to five 42-day cycles, followed by ponatinib monotherapy. Patients received 12 doses of intrathecal chemotherapy as central nervous system prophylaxis.

The study’s primary endpoints were complete molecular response—defined as absence of a detectable BCR-ABL1 transcript by polymerase chain reaction (PCR) at a sensitivity of 0.01%—in patients with newly diagnosed disease, and overall response in patients with relapsed or refractory disease or chronic myeloid leukemia in lymphoid blast phase.

A complete molecular response occurred in 87% of the 38 newly diagnosed patients who were evaluable, in 79% of the 13 evaluable patients with relapsed or refractory disease, and in 33% of the six evaluable patients with CML in lymphoid blast phase. An overall response occurred in 92% of the evaluable patients with relapsed or refractory disease and in 83% of the evaluable patients with CML in lymphoid blast phase.

Infection was the most common grade 3 to grade 4 adverse event, occurring in 37% of patients, followed by increased amylase or lipase concentration in 8%, increased alanine aminotransferase or aspartate aminotransferase concentration in 7%, pain in 7%, and hypertension in 7%.

Tremor led to blinatumomab discontinuation in one patient, while three patients discontinued ponatinib secondary to cerebrovascular ischemia, portal vein thrombosis, or coronary artery stenosis. No treatment-related deaths were reported.

“The chemotherapy-free combination of ponatinib and blinatumomab resulted in high rates of complete molecular response in patients with newly diagnosed and relapsed or refractory Ph+ [ALL],” Dr. Jabbour and colleagues concluded. “Patients with newly diagnosed Ph-positive [ALL] could be spared the toxicities associated with chemotherapy and the need for allogeneic hematopoietic stem-cell transplantation in first response.”


Jabbour E, Short NJ, Jain N, et al. Ponatinib and blinatumomab for Philadelphia chromosome-positive acute lymphoblastic leukaemia: a US, single-centre, single-arm, phase 2 trial. Lancet Haematol. 2023;10(1):e24-e34.

Editorial Board