A combo of ponatinib (Iclusig) and blinatumomab (Blincyto) attained high rates of total molecular remission and durable responses in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL), according to results of some phase II study.
Newly diagnosed Ph+ ALL patients treated with the combination had complete response and total molecular response levels of 100percent and 85 percent, respectively, while patients with relapsed/refractory disease had speeds of 89percent and 88 percent, reported Nicholas Short, MD, of the MD Anderson Cancer Center in Houston.
“The combination of ponatinib and blinatumomab appears to be a promising regimen in both frontline and relapse/refractory Ph+ ALL, as well as in chronic myeloid leukemia in lymphoid blast phase,” said Short during a presentation at the American Society of Clinical Oncology digital assembly. “Given the particularly favorable outcomes in patients with newly diagnosed Ph+ ALL who are not transplanted in first remission, these data suggest this regimen may serve as an effective transplant-sparing regimen in this population.”
The present standard of care for the majority of patients with newly diagnosed Ph+ ALL is a mixture of chemotherapy and a BCR-ABL tyrosine-kinase inhibitor (TKI), Short pointed out.
While a combination of chemotherapy and first- and – second-generation TKI has attained 5-year overall survival (OS) levels of 35%-50%, relapses are common and often driven by the development of T315I mutations from the BCR-ABL gene, which might be prevalent in as many as 75percent of instances, he noted.
Ponatinib is a third-generation TKI designed to potently inhibit BCR-ABL, also has activity against these T315I mutations. Blinatumomab has also been proven to be an effective monotherapy in treating relapsed/refractory Ph+ ALL, and in conjunction with the TKI dasatinib (Sprycel) in treating newly diagnosed patients. Thus, Short and coworkers wanted to assess the mixture of ponatinib and blinatumomab in recently diagnosed and relapsed/refractory Ph+ ALL patients.
The trial comprised 35 patients treated with ponatinib and blinatumomab, such as 20 with newly diagnosed Ph+ALL in the first line, 10 with relapsed/refractory Ph+ALL, and five with CML-Lymphoid blast phase crisis (CML-LBP).
The trial endpoint was complete molecular reaction for recently diagnosed patients and overall reaction for patients using relapsed/refractory disease. Secondary endpoints included event-free and OS, in addition to safety.
Overall, the study cohort had a whole response or pathologic complete response rate of 96%, a major molecular response of 91 percent, and total molecular reaction rate of 79%. )
In addition to the high response rates in frontline and relapsed/refractory Ph+ ALL, Short and colleagues reported patients with CML-LBP experienced a complete or pathologic complete response rate of 100 percent, a major molecular response speed of 60%, and complete molecular response rate of 40%. )
After a median followup of