Chemotherapy Plus Ponatinib Followed by Transplant Well-Tolerated in Adults With Philadelphia–Positive ALL

The combination of chemotherapy with ponatinib followed by allogeneic hematopoietic stem cell transplant (alloHSCT) is well-tolerated and demonstrated promising event-free survival (EFS) in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph⁺ ALL), according to a phase 2 trial.

The phase 2 PONALFIL trial enrolled 30 adult patients with newly diagnosed Ph+ ALL who were treated with a combination of ponatinib (30 mg/d) and standard induction and consolidation chemotherapy, followed by alloHSCT. The primary end points of the study were hematologic and molecular response before alloHSCT, and EFS, with molecular relapse considered as an event.

All of the 30 patients exhibited hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response, 6 in major molecular response). For 18 of the patients who received alloHSCT, no tyrosine kinase inhibitor was given following the transplant. At a median follow-up duration of of 2.1 years, 29 patients were alive. The 3-year EFS and overall survival (OS) were 70% (95% confidence interval [CI], 51 to 89) and 96% (95% CI, 89 to 100), respectively. 1 patient died of graft-versus-host disease, and 5 patients exhibited molecular relapse after alloHSCT.

The most frequent grade 3/4 adverse events were hematologic (42%), infectious (17%), and hepatic (22%), with only 1 vascular occlusive event.

“In conclusion, our trial yielded good results in terms of the efficacy and tolerability of the combination of ponatinib and standard induction and consolidation chemotherapy followed by alloHSCT in adults up to age 60 years with newly diagnosed Ph⁺ ALL,” the study authors concluded. “It also showed that a pre-emptive strategy for ponatinib after transplantation is feasible and allows a reduction of ponatinib exposure in a significant number of patients.”

Source:

Ribera JM, García-Calduch O, Ribera J, et al. Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome–positive acute lymphoblastic leukemia. Blood Advances. 2022;6(18):5395-5402. doi:10.1182/bloodadvances.2022007764