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 StephensShin Mineishi, Ryotaro Nakamura, Yi Bin Chen, Bruce R. Blazar, Jonathan Gutman, Steven M. Devine

Research output: Contribution to journalArticle

115 Scopus citations

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 newonsetgraftversus-host disease (GVHD) after anti-PD-1.Seventeen(55%)patientsdeveloped treatment-emergent GVHD after initiationof anti-PD-1 (6 acute, 4overlap, and7 chronic), with onset after amedian 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.

Original languageEnglish (US)
Pages (from-to)221-228
Number of pages8
JournalBlood
Volume130
Issue number2
DOIs
StatePublished - Jul 13 2017

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Haverkos, B. M., Abbott, D., Hamadani, M., Armand, P., Flowers, M. E., Merryman, R., Kamdar, M., Kanate, A. S., Saad, A., Mehta, A., Ganguly, S., Fenske, T. S., Hari, P., Lowsky, R., Andritsos, L., Jagasia, M., Bashey, A., Brown, S., Bachanova, V., ... Devine, S. M. (2017). PD-1 blockade for relapsed lymphoma post-allogeneic hematopoietic cell transplant: High response rate but frequent GVHD. Blood, 130(2), 221-228. https://doi.org/10.1182/blood-2017-01-761346