A phase IIa study of the anti‐ PD ‐ L1 antibody avelumab in relapsed/refractory PTCL : The AVAIL ‐T trial

Peripheral T-cell lymphomas (PTCL) are rare chemoresistant malignancies with poor outcomes, necessitating novel therapies. The programmed death-1 (PD-1)/programmed death ligand 1 (PD-L1) axis is frequently overexpressed in PTCL and represents a potential therapeutic target; however, PD-L1 inhibition has not been explored. We conducted a phase IIa trial evaluating avelumab, an anti-PD-L1 antibody, in relapsed/refractory PTCL. The primary end-point was overall response. Translational substudies included PD-L1 expression, circulating tumour DNA and baseline mass cytometry in a subset of patients. Of 35 recruited patients, 32 initiated treatment, although 13 discontinued early due to progression before the 3-month evaluation. Intention-to-treat analysis showed an overall response rate of 14.3%, median progression-free survival of 2.8 months (95% confidence interval [CI]; 1.8-3.4) and median overall survival of 10.3 months (95% CI; 6.0-12.3). In the five responding patients, median duration of response was not reached (12-month duration of response [DoR] rate 60% [95% CI; 13-88]). In a subset of patients, mass cytometry revealed marked perturbations in circulating T-cell subsets. Pathogenic variants detected in cell-free deoxyribonucleic acid (DNA) underscore the utility of liquid biopsy in PTCL, and longitudinal analysis revealed clonal dynamics. While avelumab demonstrated durable responses in a minority, most patients progressed early. Further studies are needed to define mechanisms of response and develop predictive biomarkers to guide strategies.