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

Bradley M. Haverkos, Diana Abbott, Mehdi Hamadani, Philippe Armand, Mary E. Flowers, Reid Merryman, Manali Kamdar, Abraham Sebastian Kanate, Ayman Saad, Amitkumar Mehta, Siddhartha Ganguly, Timothy S. Fenske, Parameswaran Hari, Robert Lowsky, Leslie Andritsos, Madan Jagasia, Asad Bashey, Stacey Brown, Veronika Bachanova, Deborah Stephens, Shin Mineishi, Ryotaro Nakamura, Yi-Bin Chen, Bruce R. Blazar, Jonathan Gutman and Steven M. Devine

Key points

  • Checkpoint blockade via anti-PD-1 mAbs was associated with a high overall response rate in relapsed Hodgkin lymphoma allo-HCT patients.

  • Checkpoint blockade via anti-PD-1 mAbs after allo-HCT can be complicated by rapid onset of severe and treatment refractory GVHD.

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.

  • Submitted January 13, 2017.
  • Accepted April 24, 2017.