Real-world Efficacy and Safety of Flumatinib as the First-line Treatment in Patients With de novo Philadelphia-positive Acute Lymphoblastic Leukemia.

Background: The real-world data of flumatinib, a China-developed second-generation tyrosine kinase inhibitors (TKI), on Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is limited. This study evaluated the efficacy and safety of flumatinib combined with chemotherapy as first-line therapy for Ph+ ALL.

Methods: This multicenter retrospective study included 65 adults with de novo Ph+ ALL treated with flumatinib (600 mg/day) plus intensive chemotherapy. Outcomes included complete remission (CR), CR with minimal residual disease negativity detected by multiparameter flow cytometry (CR _flow-), overall survival (OS), event-free survival (EFS), and adverse events (AEs). Survival and prognostic factors were analyzed using the Kaplan-Meier method.

Results: CR and CR _flow- were achieved in 96.9% (63/65) and 58.5% (38/65) of patients postinduction, respectively. At 24 months, OS and EFS were 87.4% and 62.6%, respectively. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) improved EFS (P < .0001) and tended to improve OS (P = .0503). Common hematologic AEs included neutropenia (93.8%) and thrombocytopenia (76.9%); severe nonhematologic AEs were rare. Relapses (17/63) predominantly associated with T315I (10/19) and Y253H (5/19) mutations. Age ≥ 35 years, BCR/ABL1^P210, and ABL1 Y253H mutation were significantly associated with worse OS. Meanwhile, female, ABL1 Y253H mutation, ABL1 T315I mutation, and failure with achievement of MMR after the first course of consolidation therapy were risk factors for EFS.

Conclusions: Flumatinib-based regimens demonstrated high efficacy and tolerable toxicity in Ph+ ALL, which was comparable to other second-generation TKIs. T315I and Y253H mutations were key drivers of relapse. Although allo-HSCT enhanced survival, longer follow-up period and prospective trials are warranted to validate these findings.