Tyrosine kinase inhibitors, low intensity chemotherapy and allohct for adults with Philadelphia-positive acute lymphoblastic leukemia. Results of the polish adult leukemia group (PALG) ALL7 protocol

Abstract

Abstract Introduction The prognosis of patients with Philadelphia-positive acute lymphoblastic leukemia (Ph+ ALL) improved with the introduction of tyrosine kinase inhibitors (TKI). The goal of this study was to evaluate results of the Polish Adult Leukemia Group (PALG) ALL7 protocol, using imatinib in parallel to low intensity chemotherapy and to identify prognostic factors. Patients and methods Ninety-two patients aged 54 (18-79) years, including 47% males treated between 2018 and 2022 were included in the analysis. Induction therapy was restricted to imatinib (or dasatinib in case of central nervous system involvement), vincristine and dexamethasone. Patients achieving complete remission (CR) proceeded to 1-6 cycles of consolidation, including TKI + methotrexate, cytarabine, PEG-Asparaginase, followed by allogeneic hematopoietic cell transplantation (alloHCT) in all eligible patients, TKI-based maintenance or both. CD20+ individuals were additionally treated with rituximab. All patients received intrathecal chemotherapy to prevent CNS relapse. Results Complete remission rate was 97%. Two patients experienced primary resistance, one died of pneumonia. AlloHCT was applied to 56% of patients. The probability of overall survival (OS) and progression-free survival (PFS) at 3 years was 62% (+/-6) and 59% (+/-6), respectively. OS rates were similar for patients <55 y.o. and ≥55 y.o. (56% vs. 69%, p=0.47). In univariate analysis OS rate was increased for female compared to male patients (75% vs. 48%, p=0.04) while decreased for those with additional cytogenetic abnormalities (44% vs. 76%, p=0.05) and WBC >30 x109/L (50% vs. 73%, p=0.04). In multivariate model all these factors were independently associated with the risk of overall mortality (female gender, HR=0.38, p=0.02; additional cytogenetic aberrations, HR=2.72, p=0.04; high WBC, HR=2.74, p=0.01). Conclusions PALG ALL7 protocol based on TKI with low intensity chemotherapy and intention of alloHCT for all eligible patients is associated with very high CR rate and encouraging survival regardless patient age. Patients with high initial WBC and the presence of additional cytogenetic abnormalities may require more intensive, personalized approach.