Comparison of the Efficacy and Safety of Ponatinib and Dasatinib in Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia With Central Nervous System Relapse: A Retrospective Study.

Introduction: Central nervous system leukemia (CNSL) is the most common extramedullary relapse site in patients with Philadelphia chromosome-positive (Ph-positive) acute lymphoblastic leukemia (ALL), with a poor prognosis and high relapse rate.

Methods: We characterized the clinical data of 21 Ph-positive B-ALL patients to analyze the efficacy and safety of ponatinib for patients with central nervous system relapsed Ph-positive ALL retrospectively.

Results: There were 11 males and 10 females in the cohort, and their median age was 45 (9-58) years old. The total CR (complete remission) rate was 90.5%. All 9 patients achieved CR in the ponatinib group, and 10 patients achieved CR in the dasatinib group (100% vs 83.3%, respectively;  = .486) and minimal residual disease-positive CR in the ponatinib group and dasatinib group (88.9% vs 58.3%,  = .178). The medium time after achieving CR was 5 and 8 weeks ( = .047). The total median overall survival (OS) was 31.1 months, and the 3-year OS was 49.0%. The median relapse-free survival (RFS) was 31.0 months, and the 3-year RFS was 45.2%. Patients in the ponatinib group showed a significantly longer OS than those patients in the dasatinib group with (medium OS not reached vs 27.6 months,  = .045) or without (medium OS not reached vs 27.6 months,  = .039) T315I mutations. The median RFS between the ponatinib group and the dasatinib group with T315I was not reached and 16.2 months,  = .065. The median RFS between the ponatinib group and the dasatinib group without T315I was not reached and 16.2 months,  = .036. No treatment-related deaths were observed during the therapy.

Conclusion: (1) Ph-positive CNSL patients seemed to have a high rate of response and postinduction MRD negativity with ponatinib and dasatinib, but ponatinib seemed to show a shorter time to achieve remission than dasatinib. (2) Ponatinib maintenance treatment might show superior survival for Ph-positive CNSL patients with or without the T315I mutation. (3) Ponatinib and dasatinib seemed to be both safe for the clinical application of Ph-positive CNSL.