Multicenter phase 2a study of avelumab in relapsed or refractory peripheral T-cell lymphoma

Peripheral T-cell lymphomas (PTCL) are chemoresistant malignancies with poor outcomes. The PD-(L)1 axis is frequently overexpressed in PTCL. The multicenter phase 2a AVAIL-T study in the UK evaluated the anti-PD-L1 antibody avelumab in relapsed/refractory (R/R) PTCL. The primary endpoint was overall response rate (ORR). Among 32 patients initiating treatment, 13 discontinued avelumab due to progression within 3 months. Intention-to-treat analysis showed an ORR of 14.3%, median-progression-free survival of 2.8 months (95% CI 1.8-3.4) and median overall of 10.3 months (6.0-12.3). In the five responding patients, median duration of response was not reached (60% response rate at 12 months). In a subset of patients, mass cytometry revealed marked perturbations in circulating T-cell subsets. Pathogenic variants detected in cell-free DNA underscore the utility of liquid biopsy in PTCL. The authors conclude that while avelumab demonstrated durable responses in a minority of patients, most patients progressed early (graphical abstract).