Isatuximab monotherapy in patients with refractory T-acute lymphoblastic leukemia or T-lymphoblastic lymphoma: Phase 2 study.

The poor prognosis of acute T-cell lymphoblastic leukemia (T-ALL) and T-cell lymphoblastic lymphoma (T-LBL) in older adults and patients with relapsed/refractory illness is an unmet clinical need, as there is no defined standard of care and there are few treatment options. Abnormally elevated CD38 expression in T-ALL and T-LBL is associated with tumor expansion and disease development, making CD38 a potential target for anti-T-ALL and T-LBL treatment. Isatuximab is a monoclonal antibody that binds to a specific epitope on CD38. The purpose of the study was to assess the efficacy and safety of isatuximab monotherapy in a phase 2, multicenter, one-arm, open-label study in patients with relapsed or refractory T-ALL or T-LBL (Clinical Trials.gov identifier NCT02999633). The primary endpoint was to assess the efficacy of isatuximab by overall response rate (ORR). An interim analysis based on the efficacy and safety of isatuximab in the first 19 patients enrolled was scheduled, however only 14 patients were enrolled in the study. No patient achieved complete response (CR) or CR with incomplete peripheral recovery. Most patients (11 [78.6%]) developed progressive disease and had progressive disease as their best response. A total of 10 (71.4%) patients had treatment emergent adverse events considered treatment-related, with infusion reactions as the most frequent drug-related TEAE, occurring in 8 (57.1%) patients. Despite the low efficacy of isatuximab in the current study, it is likely that the use of immunotherapy medication in T-ALL will be expanded through logically targeted approaches, together with advances in the design of T-cell therapy and clinical experience and will provide restorative options beyond chemotherapy and targeted treatments.