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.

Authors

Institutions

Publication Details

Journal
British Journal of Haematology
Published
2026-09-18
DOI
https://doi.org/10.1111/bjh.70828
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
0.00

Funders

Controls
|||
ALL TIME
JAN
FEB
MAR
APR
MAY
JUN
JUL
AUG
SEP
article

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

Nimish Shah, Susann Lehmann, Matthew A. Timmins, Charlotte Gaskell et al.
British Journal of Haematology
Lymphoma Diagnosis and Treatment
article

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

Nimish Shah, Susann Lehmann, Matthew A. Timmins, Charlotte Gaskell, Nagesh Kalakonda, Nadia Nawaz, Kim Linton, Aimee Jackson, Pam McKay, Kate Cwynarski, Matthew J. Ahearne, Christopher S. Trethewey, Caroline Cowley, Andrew Davies, Simon D. Wagner, Dima El‐Sharkawi, Christopher P. Fox, Graham P. Collins, David Lewis, Paul Fields, Michael Quinn, Sonia Fox, Ram Malladi, Rod Johnson, Naeem Khan, Clare Morland, Louise Hopkins, Marc Wadsley, Jacqueline Shaw
article en

Abstract

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.

British Journal of Haematology
Belfast Health and Social Care Trust (GB), University College London Hospitals NHS Foundation Trust (GB), University of Nottingham (GB), University of Liverpool (GB), University of Leicester (GB), Guy's and St Thomas' NHS Foundation Trust (GB), Wellcome/MRC Cambridge Stem Cell Institute (GB), University of Cambridge (GB), Leeds Teaching Hospitals NHS Trust (GB), Norfolk and Norwich University Hospitals NHS Foundation Trust (GB), Beatson West of Scotland Cancer Centre (GB), University Hospitals of Leicester NHS Trust (GB), Cambridge University Hospitals NHS Foundation Trust (GB), Royal Marsden Hospital (GB), The Christie NHS Foundation Trust (GB), Cancer Research UK Clinical Trials Unit (GB), Oxford University Hospitals NHS Trust (GB), NIHR CRUK Experimental Cancer Medicine Centre (GB), Plymouth Hospital (GB), NIHR Leicester Biomedical Research Centre (GB), University Hospitals Plymouth NHS Trust (GB), University College London (GB), University of Birmingham (GB)
Pfizer
Openalex Percentile: Top 11%
Lymphoma Diagnosis and Treatment
DOIOpen Access PDFOpenAlex
AI Navigator

Ask Laika to Summarize, Analyze, and Connect papers live on the map.

Summarize Papers & Methodologies

Extract key findings, datasets, and comparative methods across publications.

Benchmark Rankings & Visual Analytics

Rank top research institutions, authors, funders, topics, and journals by Field-Weighted Citation Impact (FWCI) and paper volume with instant charts.

Connect Distant Disciplines

Bridge topological clusters on the map to find hidden collaborative intersections.