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Remission from B-Cell ALL with Chemo-Free Induction Therapy
Tyrosine kinase inhibitors (TKI) targeting BCR-ABL are an integral component of initial therapy for Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Investigators from the multicenter, phase 2 D-ALBA trial reported long-term outcomes for 63 patients (age range, 24–82; median, 54) treated with the TKI dasatinib plus the CD19/CD3 T-cell–engaging bispecific monoclonal antibody blinatumomab. Patients received 12-week cycles of corticosteroids for 7 days, dasatinib (140 mg/day) plus corticosteroids for 23 days, and dasatinib alone for 54 days. Daily dasatinib was continued during consolidation with 2 or more cycles of blinatumomab. Central nervous system prophylaxis was administered via lumbar puncture at multiple time points. Serial minimal residual disease was analyzed in bone marrow by reverse transcriptase-polymerase chain reaction.
The complete remission rate was 98%. The molecular response rate was 60% following cycle 2 of blinatumomab (previously reported; N Engl J Med 2020; 383:1613) and increased to 93% at 12 months. At a median follow-up of 53 months, disease-free survival (DFS) was 75.8%, and overall survival was 80.7%. DFS was significantly lower in patients without molecular response at the end of induction and in those with the IKZF1plus mutation. Of 29 patients treated with ongoing TKI therapy but not cytotoxic chemotherapy or stem cell transplantation, 28 remained in complete hematologic remission at a median 48 months' follow-up.
Comment
The long-term results of the D-ALBA trial confirm the efficacy of chemotherapy-free induction and maintenance therapy in adults with Ph+ ALL. The DFS was 100% for patients in molecular remission at the end of induction, which confirms the prognostic benefit of this metric. The combination of ponatinib plus blinatumomab has shown similar promising results, and additional multicenter chemotherapy-free and risk-adapted trials are in progress.
Citation(s)
Author:
Foà R et al.
Title:
Long-term results of the dasatinib-blinatumomab protocol for adult Philadelphia-positive ALL.
Source:
J Clin Oncol
2023
Dec
21; [e-pub].
(Abstract/FREE Full Text)
Empfohlen von
Michael E. Williams, MD, ScM