EHA 2022 | Ponatinib and blinatumomab for the treatment of Ph+ ALL

Ponatinib and blinatumomab is a chemotherapy-free combination for patients with Philadelphia chromosome positive ALL. We’re reporting updated data from this ongoing Phase II study. We’ve reported 55 patients: 35 patients with newly diagnosed Ph positive ALL. 14 patients with relapsed/refractory Ph positive ALL, and 6 patients with CML and lymphoid blast phase. Overall, we see very high rates of response and particularly MRD negative responses. So for example, in the newly diagnosed cohort, after just one cycle of the chemotherapy-free combination, we see 64% of patients achieving a complete molecular response. Meaning that they have no detectable PCR for BCR/ABL. At any point over the course of therapy, the rate of complete molecular response for those patients is 85%. We also see very high rates of molecular response for the relapsed/refractory Ph positive ALL cohort. Although, the responses are a bit lower in the CML lymphoid blast phase.

Overall, we’re very encouraged by the responses. Particularly in the frontline cohort and the durability of those responses. So far we’ve only transplanted one patient, in the newly diagnosed cohort, and there have been no relapses. So that’s translated to a two-year event free and overall survival rate of 93%. Overall, the regimen appears to be safe. The toxicity profile is consistent with the known single agent toxicity of these individual drugs and was manageable with the dose mitigation strategies that we have. Specifically, we start ponatinib at 30 milligrams daily, and then dose reduced to 15 milligrams once patients achieve a complete molecular response. And that does mitigate some of the known toxicities associated with ponatinib.