ASCO 2021 | Blinatumomab plus ponatinib for Ph+ ALL

Yeah, so, this is a study evaluating a chemotherapy-free regimen blinatumomab in combination with ponatinib in patients with Ph-positive ALL, and so, we’re enrolling any adult patient with either newly diagnosed or relapsed/refractory ALL. There’s a lot of interest in these chemotherapy-free regimens in this disease. Obviously ponatinib is a very potent TKI. Blinatumomab was very effective in the relapsed/refractory setting and there’s some good early data for dasatinib and blinatumomab in newly diagnosed AML. So, that was kind of the rationale for combining these particularly with the ability for ponatinib to target and treat, being active against T315I mutations, which we know cause resistance to other types of TKIs.

So, in this study, we give patients five cycles of blinatumomab in combination with ponatinib. The ponatinib was initially started at 30mg daily and then decreased to 15mg once a patients achieve a complete molecular response. Those are given in combination again for the five cycles and then patients receive five years of ponatinib maintenance at 15mg daily. They also receive 12 doses of intrathecal chemotherapy.

So far, we’ve treated 35 patients overall, 20 in the frontline setting, 10 relapsed refractory, and then we also included patients with CML and lymphoid blast phase cause these behave similarly to Ph-positive ALL. So overall, the response, the data have been very encouraging. All but one patient who have responded to the regimen. It was one patient with multiply relapsed/refractory disease. So among the frontline cohort of 20 patients, all of them achieved a remission, 85% of which achieved a complete molecular response and the relapsed/refractory setting, 89% achieved a response and of the, among the responders 88% achieved a complete molecular response.

And so, in the frontline setting, these responses translated to a two-year estimated overall survival of 93%. Notably, only one patient died. This is a patient who died actually in remission. So, there have been no relapses in the frontline setting and also no patients have undergone stem cell transplant. In the relapsed/refractory setting, the two-year event-free survival is 41% to your overall survival, 53%. And overall toxicity is as expected with both drugs. No patients had to stop therapy due to blinatumomab. There were two patients who had to, who came off study, one due to stroke, one due to development of a DVT.

But overall, we believe these data are very encouraging, particularly in the frontline setting where we had a 100% response rate, 85% complete molecular remission rate, no patients relapsing, and none of whom were transplanted. So overall, I think that this potentially represents a very promising chemotherapy-free and transplant sparing regimen for patients with Ph-positive ALL.