PD-1 blockade for relapsed lymphoma post–allogeneic hematopoietic cell transplant: high response rate but frequent GVHD

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.

Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

“…In another study by Haverkos et al , 28 patients received nivolumab at the dose of 3 mg/kg and 3 patients received pembrolizumab at 200 mg/kg. Out of thirty-one, 17 patients developed GVHD (10 acute and 7 chronic cases of GVHD) (7). It is noteworthy that in both studies (Herbaux et al and Haverkos et al) a majority of patients who developed CPI related GVHD, had a prior history of GVHD (12 out of 17 cases in Haverkos et al and all the 6 cases in Herbaux et al ).…”

Shortened-Duration Tacrolimus after Nonmyeloablative, HLA-Haploidentical Bone Marrow Transplantation

“…With this PTCy-based platform, shortened-duration IS may allow for earlier or more effective administration of preemptive therapies for relapse reduction, such as cellular immunotherapies and checkpoint inhibitors [25–27]. …”

Strategies for Recognizing and Managing Immune-Mediated Adverse Events in the Treatment of Hodgkin Lymphoma with Checkpoint Inhibitors

“…Herbaux et al reported that 30% (6/20) of patients experienced acute GVHD, with three patients dying from treatment‐related causes. However, in the Herbaux study, GVHD was observed only in patients with prior acute GVHD, whereas in the Haverkos report, 71% of patients who developed GVHD after PD‐1 blockade had prior acute or chronic GVHD . Additional long‐term data are needed to fully evaluate the risks and benefits of using PD‐1 inhibitor therapy after allo‐HCT.…”

“…In both studies, prolonged survival and a high overall clinical response (overall response 77% and 95%) were observed, indicative of an activated graft‐versus‐tumor effect, but outcomes were frequently complicated by the onset of treatment‐related GVHD . Haverkos et al reported that 55% (17/31) of patients developed either acute or chronic GVHD after PD‐1 inhibition, with eight treatment‐related deaths; 94% of GVHD cases occurred after one to two doses of anti‐PD‐1 therapy. Herbaux et al reported that 30% (6/20) of patients experienced acute GVHD, with three patients dying from treatment‐related causes.…”