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Results from a phase 2 study showed that a 2-step induction regimen involving dasatinib and intensive chemotherapy was associated with high rates of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients younger than 65 years with Philadelphia chromosome-positive (Ph+), newly diagnosed acute lymphoblastic leukemia (ALL), as well as improved 3-year overall survival (OS) rates for those undergoing allo-HSCT compared with those who did not. These findings were presented during the Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress.1
While the standard-of-care in Japan for the treatment of younger patients with newly diagnosed Ph+ ALL is allo-HSCT preceded by imatinib plus intensive chemotherapy induction therapy, 30% to 40% of patients treated with this regimen in clinical trials were unable to undergo allo-HSCT due to older age, early relapse, or therapy-related death.2 Hence, less toxic and more effective pretransplant regimens are needed for this population of patients.
In an open-label, single-arm, multicenter, phase 2 Japan Adult Leukemia Study Group (JALSG) Ph+ALL213 study (UMIN000012173), patients with newly diagnosed Ph+ALL aged 15 to 64 years received 7 days of prephase therapy with prednisone, followed by the following steps: (1) induction therapy involving treatment with dasatinib plus prednisone; (2) intensive consolidation therapy including dasatinib, cyclophosphamide, daunorubicin, vincristine and prednisone, followed by 4 alternating cycles of 2 different consolidation therapy regimens. Maintenance therapy involved treatment with dasatinib, vincristine, and prednisone; however, patients who achieved hematologic complete remission (HCR) following consolidation therapy who had an appropriate donor underwent allo-HSCT during consolidation. The primary study endpoint was 3-year event-free survival (EFS) following induction. Secondary study endpoints included HCR, safety, and the efficacy of allo-HSCT (ie, relapse-free survival, relapse rate, and non-relapse mortality).1,3
Previously reported results demonstrated that both 3-year EFS and 3-year OS were improved for the overall study population of patients with newly diagnosed Ph+ ALL receiving dasatinib-based therapy compared with imatinib-based induction therapy.3
The analysis reported here included 78 of the 81 patients enrolled in this study, patients had a median age of 45 years and 32.1% of patients were 55 years or older. The rate of HCR after induction therapy was 100%, and 21.8%, 52.6% and 57.7% achieved molecular complete remission (MCR) after induction therapy, intensive consolidation therapy, and the first cycle of consolidation therapy, respectively. Of the 58 patients who underwent allo-HSCT, 75.9% had achieved MCR prior to allo-HSCT. No induction therapy-related deaths were reported.
Of the 58 (74.4%) patients who underwent allo-HSCT, the rates of relapse, relapse mortality, and transplant-related relapse mortality were 15.5%, 8.6%, and 10.3%, respectively. A cross-study comparison of these results with the PH+ALL202 study involving imatinib-based induction therapy did not show significant differences in these rates.1,2
At a median follow-up of 4 years, the rates of 3-year EFS and 3-year OS for the overall study group and the subgroup of those undergoing allo-HSCT were 66.2% and 80.5% compared with 74.1% and 84.1%, respectively.
In their concluding remarks, the study authors noted that “this study demonstrated [dasatinib]-combined 2-step induction improved pretransplant treatment, which facilitated [allo-HSCT] and resulted in significantly improved survival.”
- Sugiura I, Doki N, Hata T, et al. Allogeneic hematopoietic stem cell transplantation following dasatinib-based two-step induction for Philadelphia chromosome-positive acute lymphoblastic leukemia: Results of the JALSG PH+ALL213 study. Presented at: Virtual Edition of the 25th European Hematology Association (EHA) Annual Congress; June 2020. Abstract S114.
- Hatta Y, Mizuta S, Matsuo K, et al. Final analysis of the JALSG Ph+ALL202 Study: Tyrosine kinase inhibitor-combined chemotherapy for Ph+ALL. Ann Hematol. 2018;97:1535-1545.
- Sugiura I, Doki N, Hata T, et al. Dasatinib-based two-step induction prior to allogeneic hematopoietic cell transplantation for newly diagnosed Philadelphia chromosome-positive acute lymphoblastic leukemia: Results of the JALSG Ph+ALL213 Study. Blood. 2019;134(suppl_1):Abstract 614.
This article originally appeared on Cancer Therapy Advisor