Dasatinib-Containing Induction Therapy Associated With High Rates of Allogeneic HSCT in Newly Diagnosed Ph+ ALL

The following article features coverage from the European Hematology Association 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

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.”

Read more of Cancer Therapy Advisor‘s coverage of the EHA virtual meeting by visiting the conference page.

References

1. 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.
2. 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.
3. 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.