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

Publication Type:

Journal Article

Source:

Blood (2017)

Abstract:

Given the limited treatment options for relapsed lymphoma post allogeneic hematopoietic cell transplantation (allo-HCT) and the success of PD-1 blockade in classical Hodgkin lymphoma (cHL) patients, anti-PD-1 monoclonal antibodies (mAbs) are increasingly being used off-label following 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. Median follow up was 428 days (range 133-833) after the first dose of anti-PD-1. Overall response rate (ORR) was 77% (15 complete response (CR) 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 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.