Clinical Experience with Venetoclax in Combination with Chemotherapy for Relapsed or Refractory T-Cell Acute Lymphoblastic Leukemia

Abstract Background Patients with relapsed or refractory (R/R) T-cell acute lymphoblastic leukemia/lymphoma (T-ALL) have dismal outcomes. Preclinical studies suggest that T-ALL cells are sensitive to BCL2 inhibition. Clinical activity of venetoclax, a selective BCL2 inhibitor, in T-ALL is unknown. Patient and Methods We retrospectively reviewed the efficacy and safety of venetoclax in combination with chemotherapy for patients with R/R T-ALL treated at our institution. Results Thirteen patients with R/R T-ALL with a median age of 46 years (range, 20-75) were treated with venetoclax plus chemotherapy. Five (38%) patients had early T-cell precursor (ETP) ALL. Patients had received a median of 2 prior lines of therapy (range, 1-11). Venetoclax at a median dose of 200 mg daily for 21 days, generally with concomitant azole antifungal, was combined with various agents including Hyper-CVAD, asparaginase, nelarabine, decitabine or other intensive chemotherapy. Among 10 patients evaluable for marrow response, 6 (60%) achieved a remission with bone marrow blasts Conclusion Combination therapy with venetoclax shows promising clinical efficacy in R/R T-ALL. Further studies are warranted to evaluate the clinical benefit of BCL2 inhibitors in T-ALL.