Effect of Prophylactic Post-transplant Ponatinib Administration on Outcomes in Patients With Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia

The effect of post-transplant ponatinib maintenance therapy on outcomes after allogeneic hematopoietic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia has remained unknown. The presented results suggest that survival in the ponatinib group was better than that in the non-ponatinib group and that ponatinib maintenance therapy is safe. The post-transplant ponatinib maintenance strategy might be promising. Background: The objective of the present retrospective study was to evaluate the effect of ponatinib administration as maintenance therapy on the outcomes after allogeneic hematopoietic stem cell transplantation in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia. Patients and Methods: We retrospectively analyzed the data from 34 consecutive patients treated at our institution from January 2008 to June 2019. We had administered post-transplant tyrosine kinase inhibitors preemptively before December 2017. Thereafter, we had initiated the prophylactic use of post-transplant ponatinib. The initial ponatinib dose was 15 mg/d. Ponatinib plasma trough levels were measured using the liquid chromatography-tandem mass spectrometry method 8 days after the first administration and subsequently. Results: Nine patients received ponatinib maintenance. The 2-year overall survival and leukemia-free survival in the ponatinib maintenance group tended to be better than that in the non-ponatinib group (100% vs. 70.5%, P = .10; and 100% vs. 50.8%, P = .02, respectively). In the first 7 of the 9 consecutive patients, the median plasma concentration after ponatinib administration (15 mg/d) was 15.6 ng/mL (range, 4.8-23.3 ng/mL). Although the treatment schedule for 1 patient was altered because of adverse effects (elevation of serum amylase and neutropenia), ponatinib administration was continued for all the patients, except for 1 patient with molecular relapse. One patient developed a transient elevation of serum lipase. No patient presented with any arterial occlusive events. Conclusion: Our results have indicated that the strategy of ponatinib maintenance after allogeneic hematopoietic stem cell transplantation is safe, efficacious, and promising. (C) 2020 Elsevier Inc. All rights reserved.