Results of Third-Line Therapy in Philadelphia Chromosome-Positive Adult Acute Lymphoblastic Leukemia

Background: The historical results in adults with Philadelphia chromosome (Ph)-positive acute lymphoblastic leukemia (ALL) in second relapse treated with third-line therapy (Salvage 2) are extremely poor. Using standard chemotherapy resulted in complete response rates of 20% and a median overall survival of 2 to 3 months. This may be changing with the recent availability of novel therapeutic strategies, including targeted antibodies and engineered chimeric antigen receptor T-cell therapy, as well as more potent BCR::ABL1 tyrosine kinase inhibitors. Study Aims: Analyze the outcome of adults with Ph-positive ALL with different modalities in Salvage 2. Patients and Methods: A total of 89 adults with Ph-positive ALL in Salvage 2 treated from 1992 until 2025 were analyzed. Results: The complete remission (CR) rate was 58%; the 3-year survival rate was 17%. By multivariate analysis, the most significant independent favorable predictors for CR and survival were the type of therapy utilized. Among 27 patients treated since 2017, the CR rate was 89% and the 3-year survival rate 52%. Conclusions: Adults with Ph-positive ALL in Salvage 2 receiving third-line therapy now have reasonable outcome expectations with the newer strategies available in the past decade.