A new phase II trial demonstrated that the chemotherapy-free regimen of ponatinib and blinatumomab may have 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 leukemia (ALL), according to new findings presented by Short et al at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 213).
“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,” emphasized lead study author Nicholas Short, MD, Assistant Professor in the Department of Leukemia at The University of Texas MD Anderson Cancer Center. “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[s] in these patients.”
Patients with Ph+ ALL have historically had poor long-term survival rates. Researchers have found adding tyrosine kinase inhibitors—such as ponatinib, which targets the BCR-ABL1 gene sequence—to chemotherapy can drastically improve survival. Blinatumomab is a CD19/CD3 bispecific antibody that may be effective as a single agent in relapsed or refractory Ph+ ALL.
The new trial enrolled 40 patients aged 56 years on average, who had recently been diagnosed with Ph+ acute lymphoblastic leukemia. Patients with uncontrolled cardiovascular disease or clinically significant central nervous system comorbidities were excluded from the study.
Among the patients that were evaluable for a hematologic response, 96% of them had a complete remission or complete remission with incomplete count recovery. Among the 38 patients who were evaluable for complete molecular responses, 68% of them demonstrated the complete response after one treatment cycle, and 87% of them achieved the complete response during the trial period. Molecular responses were rapid, with a majority of patients achieving complete molecular responses in the peripheral blood within 2 weeks of therapy. Only one patient underwent a stem cell transplant in their first remission.
At a median follow-up of 15 months, the patients’ 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 to 2 and consistent with known side effects of the two agents.
Disclosure: The research in this study was funded by Amgen and Takeda Oncology. For full disclosures of the study authors, visit ash.confex.com.
