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PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: high response rate but frequent GVHD. Blood 2017 07 13;130(2):221-228 PMID: 28468799 PMCID: PMC5510790

Pubmed ID

28468799

DOI

10.1182/blood-2017-01-761346

Abstract

Given the limited treatment options for relapsed lymphoma post-allogeneic hematopoietic cell transplantation (post-allo-HCT) and the success of programmed death 1 (PD-1) blockade in classical Hodgkin lymphoma (cHL) patients, anti-PD-1 monoclonal antibodies (mAbs) are increasingly being used off-label after allo-HCT. To characterize the safety and efficacy of PD-1 blockade in this setting, we conducted a multicenter retrospective analysis of 31 lymphoma patients receiving anti-PD-1 mAbs for relapse post-allo-HCT. Twenty-nine (94%) patients had cHL and 27 had ≥1 salvage therapy post-allo-HCT and prior to anti-PD-1 treatment. Median follow-up was 428 days (range, 133-833) after the first dose of anti-PD-1. Overall response rate was 77% (15 complete responses and 8 partial responses) in 30 evaluable patients. At last follow-up, 11 of 31 patients progressed and 21 of 31 (68%) remain alive, with 8 (26%) deaths related to new-onset graft-versus-host disease (GVHD) after anti-PD-1. Seventeen (55%) patients developed treatment-emergent GVHD after initiation of anti-PD-1 (6 acute, 4 overlap, and 7 chronic), with onset after a median of 1, 2, and 2 doses, respectively. GVHD severity was grade III-IV acute or severe chronic in 9 patients. Only 2 of these 17 patients achieved complete response to GVHD treatment, and 14 of 17 required ≥2 systemic therapies. In conclusion, PD-1 blockade in relapsed cHL allo-HCT patients appears to be highly efficacious but frequently complicated by rapid onset of severe and treatment-refractory GVHD. PD-1 blockade post-allo-HCT should be studied further but cannot be recommended for routine use outside of a clinical trial.

Author List

Haverkos BM, Abbott D, Hamadani M, Armand P, Flowers ME, Merryman R, Kamdar M, Kanate AS, Saad A, Mehta A, Ganguly S, Fenske TS, Hari P, Lowsky R, Andritsos L, Jagasia M, Bashey A, Brown S, Bachanova V, Stephens D, Mineishi S, Nakamura R, Chen YB, Blazar BR, Gutman J, Devine SM

Authors

Timothy Fenske MD Professor in the Medicine department at Medical College of Wisconsin
Mehdi H. Hamadani MD Professor in the Medicine department at Medical College of Wisconsin
Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-85023768076   63 Citations

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antibodies, Monoclonal
Antibodies, Monoclonal, Humanized
Antineoplastic Agents
Female
Gene Expression
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Hodgkin Disease
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
Programmed Cell Death 1 Receptor
Remission Induction
Retrospective Studies
Salvage Therapy
Survival Analysis
Transplantation Conditioning
Transplantation, Homologous
Treatment Outcome
jenkins-FCD Prod-321 98992d628744e349846c2f62ac68f241d7e1ea70