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

Abstract

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; P = .486) and minimal residual disease-positive CR in the ponatinib group and dasatinib group (88.9% vs 58.3%, P = .178). The medium time after achieving CR was 5 and 8 weeks ( P = .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, P = .045) or without (medium OS not reached vs 27.6 months, P = .039) T315I mutations. The median RFS between the ponatinib group and the dasatinib group with T315I was not reached and 16.2 months, P = .065. The median RFS between the ponatinib group and the dasatinib group without T315I was not reached and 16.2 months, P = .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.

Case report: Olverembatinib monotherapy: the chemotherapy-free regimen for an elderly patient with relapsed Ph-positive acute lymphoblastic leukemia

“…Of these patients, 88.5% (23/26) achieved CMR, and the mOS and EFS were 20 and 15.3 months, respectively ( Couturier et al, 2021 ). Additionally, ponatinib alone may show superior survival and a shorter time to achieve CMR compared to dasatinib alone for Ph + -ALL with CNS-L patients with or without the T315I mutation ( Zhu et al, 2023 ). Currently, an increasing number of studies have begun to explore the role of ponatinib as a first-line treatment for Ph + -ALL.…”

Methotrexate-Induced Subacute Combined Degeneration in Acute Lymphoblastic Leukemia with CNS Relapse May Be Reversible

“…For ALL with CNS relapse, early administration of systemic HD MTX should be considered early after the initial failure of IT chemotherapy to avoid higher cumulative MTX doses and overlapping IT and systemic exposure. In Ph+ disease, TKIs with CNS penetration are needed, and ponatinib was initiated in this case because of reported blood-brain barrier penetration, though clear evidence is lacking [55]. Although clearance of the CNS is paramount for survival, we recommend considering a cap of four twice-weekly LPs with IT chemotherapy before systemic HD MTX is administered for persistent CNS disease; however, this is only based on our expert opinion, and empirical data are lacking.…”

Drug-Induced Reorganisation of Lipid Metabolism Limits the Therapeutic Efficacy of Ponatinib in Glioma Stem Cells

“…Building on our recent study on PDGFR activation in the context of glucocorticoid signalling in GBM [ 12 ], we sought to better understand the response of GSCs to ponatinib (Iclusig ® ), a multi-target TKI used for the treatment of chronic myelogenous leukaemia (CML). Apart from BCR-ABL, it has high affinity for PDGFR, and most importantly, has demonstrated promising blood–brain barrier (BBB) penetrance in mice [ 13 ] and activity in acute lymphocytic leukaemia (ALL) patients with central nervous system (CNS) relapse [ 14 ].…”