Targeting CD38 with bispecific antibody XmAb 18968 in patients with relapsed/refractory acute myeloid leukemia and T-cell acute lymphoblastic leukemia

Why clinicians should know about it

• Picked for Hematology (paper of the day, 18 September 2026): CD38 bispecific antibody in relapsed AML and T‑ALL, phase‑1 trial

Abstract

CD38 is a transmembrane glycoprotein highly expressed in acute myeloid leukemia (AML) and T-cell acute lymphoblastic leukemia (T-ALL). XmAb18968 is a novel CD38-CD3 bi-specific T-cell engager with Fc domain modified to reduce non-selective activation of effector cells. In this phase 1 multicenter clinical trial, we evaluated the outcomes of XmAb18968 in adults with relapsed/refractory (RR) AML and T-ALL. Twenty-two patients with AML (n = 13) and T-ALL (n = 9) with a median age of 63 years (range 31-77) were enrolled. Prior lines of therapy (median 3, range 1-8) included venetoclax (77.3%), allogeneic HCT (22.7%), CD7 CAR-T cell therapy and daratumumab (11.1%). Grade ≥3 adverse events included anemia (14%), neutropenia (18%), and thrombocytopenia (14%). No grade ≥3 cytokine release syndrome or neurotoxicity was seen. Overall, 17 patients (AML = 11, ALL = 6) completed at least one cycle of therapy. Among 11 patients with RR-AML, one achieved partial remission (PR) and two achieved MRD negative complete remission (CR). In 6 patients with RR-T-ALL, 4 achieved meaningful improvement in disease burden with 1 clearance of MRD. Median OS was 8.5 months in AML and 8.7 months in T-ALL. XmAb18968 is safe and tolerable with encouraging preliminary efficacy, supporting further investigation of CD38 targeting therapies in this setting (NCT05038644).

Abstract as published, via PubMed.