The chemotherapy-free regimen of ponatinib and blinatumomab achieved high response rates and reduced the need for an allogeneic stem cell transplant for patients with recently diagnosed Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL), according to results from a Phase II trial.

One of the lead investigators, Nicholas Short, M.D., assistant professor of Leukemia, presented the findings at ASH 2022.

“Traditionally, Ph+ ALL responds poorly to standard chemotherapy and is high-risk for relapse, so these survival results and reduced need for a stem cell transplant are very encouraging,” Short said. “Not only does this regimen appear to be a safe and effective chemotherapy-free option, but it also seems to overcome the historical need for transplant in these patients.”

Patients with Ph+ ALL have historically had poor long-term survival rates. Researchers have found adding tyrosine kinase inhibitors (TKIs), such as ponatinib, to chemotherapy can drastically improve survival.

Ponatinib is a third-generation TKI that targets BCR-ABL1 and is traditionally used to treat certain types of chronic myeloid leukaemia. Blinatumomab is a CD3-CD19 bispecific antibody that is effective as a single agent in relapsed or refractory Ph+ ALL.

The trial enroled 40 patients with newly diagnosed Ph+ ALL. Patients with uncontrolled cardiovascular disease or clinically significant central nervous system comorbidities were excluded from the study.

The average age of participants was 56 years old.

Of the patients that were evaluable for a haematologic response, 96% had a complete remission or complete remission with incomplete count recovery.

Among the 38 patients who were evaluable for complete molecular response (CMR), 68% achieved CMR after one treatment cycle and 87% achieved CMR during the trial period.

Molecular responses were rapid, with a majority of patients achieving CMR in the peripheral blood within two weeks of therapy.

Only one patient underwent stem cell transplant in first remission.

At a median follow-up of 15 months, event-free and estimated overall survival was 95%.

These encouraging outcomes were observed despite the very low rate of transplant in the study.

The treatment was well tolerated, and most toxicities were grade 1-2 and consistent with known side effects of the two agents. 

Source: The University of Texas MD Anderson Cancer Center