Hypomethylating agents (HMAs) are the mainstay of therapy for older or unfit patients with AML, but responses are limited and relapse occurs. Riether et al. show that HMA treatment increases the expression of CD70 on cultured leukaemic stem cells (LSCs, the major cause of relapse) from patients with AML, leading to increased CD70/CD27 signalling. The αCD70 mAb cusatuzumab eradicated LSCs in vitro and in a patient-derived xenograft model. In a phase I/II trial in untreated older patients with AML, one dose of cusatuzumab followed by combination therapy with the HMA azacitidine reduced LSCs and led to complete remission in 66% of patients.
Nature Reviews Drug Discovery 19, 512 (2020)