Safety and efficacy of anti-programmed cell death-1 monoclonal antibodies before and after allogeneic hematopoietic cell transplantation for relapsed or refractory Hodgkin lymphoma: a multicenter retrospective study

Int J Hematol. 2020 Nov;112(5):674-689. doi: 10.1007/s12185-020-02960-4. Epub 2020 Aug 3.

Abstract

We conducted a multicenter study on anti-programmed cell death-1 monoclonal antibodies (anti-PD-1 mAbs) before/after allogeneic hematopoietic cell transplantation (allo-HCT) for Hodgkin lymphoma. Anti-PD-1 mAbs were administered to 25 patients before allo-HCT and to 20 after allo-HCT. In pre-allo-HCT setting, the median interval from the last administration to allo-HCT was 59 days. After allo-HCT, 12 patients developed non-infectious febrile syndrome requiring high-dose corticosteroid. The cumulative incidences of grade II-IV acute graft-versus-host disease (aGvHD) were 47.1%. Eight patients who had GvHD prophylaxis with post-transplant cyclophosphamide (PTCy) had less frequent aGvHD (grade II-IV, 14.6% versus 58.8%; P = 0.086). The 1 year overall survival (OS), relapse/progression, and non-relapse mortality rates were 81.3%, 27.9%, and 8.4%. In post-allo-HCT setting, the median interval from allo-HCT to the first administration was 589 days. The overall and complete response rates were 75% and 40%. At 100 days after anti-PD-1 therapy, the cumulative incidences of grade II-IV aGvHD, moderate-to-severe chronic GvHD, and grade 3-4 immune-related toxicity were 15.0%, 30.0%, and 30.0%. While the 1 year relapse/progression rate was 47.4%, the 1 year OS probability was 89.7%. In conclusion, immune-related complications were frequent despite modifications of GvHD prophylaxis or anti-PD-1 mAb dosing. In anti-PD-1-mAb-pretreated patients, PTCy-based GvHD prophylaxis may be effective.

Keywords: Allogeneic hematopoietic cell transplantation; Anti-PD-1 monoclonal antibody; Hodgkin lymphoma; Immune checkpoint inhibitor.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal / administration & dosage*
  • Antibodies, Monoclonal / adverse effects
  • Cyclophosphamide / administration & dosage
  • Female
  • Graft vs Host Disease / etiology
  • Graft vs Host Disease / prevention & control
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hodgkin Disease / mortality
  • Hodgkin Disease / therapy*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local
  • Programmed Cell Death 1 Receptor / immunology*
  • Safety
  • Survival Rate
  • Transplantation, Homologous
  • Treatment Outcome
  • Young Adult

Substances

  • Antibodies, Monoclonal
  • Immunosuppressive Agents
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Cyclophosphamide