Long-term efficacy of anti-PD1 therapy in Hodgkin lymphoma with and without allogenic stem cell transplantation

Eur J Cancer. 2019 Jul:115:47-56. doi: 10.1016/j.ejca.2019.04.006. Epub 2019 May 10.

Abstract

Introduction: Long-term efficacy of anti-PD1 therapy and the need for a consolidation with allogenic haematopoietic stem cell transplantation (allo-HSCT) remain unclear in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL).

Methods: We retrospectively analysed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcomes according to subsequent allo-HSCT.

Results: After a median follow-up of 34.3 months, the best overall response rate was 65.8%, including 38.2% complete responses (CRs). The median progression-free survival (PFS) was 12.1 months. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a partial response (PR) (median = not reached vs 9.3 months, p < 0.001). In our cohort, 13 patients who responded (i.e. in CR or PR) to nivolumab monotherapy underwent consolidation with allo-HSCT. Among responding patients, none of those who underwent subsequent allo-HSCT (N = 13) relapsed, whereas 62.2% of those who were not consolidated with allo-HSCT (N = 37) relapsed (p < 0.001). There was no difference in overall survival (OS) between the two groups. Five of 6 patients who were not in CR at the time of transplantation (4 PRs and 1 progressive disease) converted into a CR after allo-HSCT.

Conclusion: Most patients with R/R HL treated with anti-PD1 monotherapy eventually progressed, notably those who did not achieve a CR. Patients undergoing consolidation with allo-HSCT after anti-PD1 therapy experienced prolonged disease-free survival compared with non-transplanted patients, but this difference did not translate into a benefit in OS. This information should be considered when evaluating the risk/benefit ratio of allo-HSCT after anti-PD1 therapy.

Keywords: Allogenic haematopoietic stem cell transplantation; Anti-PD1; Checkpoint inhibitors; Hodgkin lymphoma; Immunotherapy; Nivolumab.

Publication types

  • Comparative Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antineoplastic Agents, Immunological / administration & dosage*
  • Antineoplastic Agents, Immunological / adverse effects
  • Disease Progression
  • Female
  • France
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Hematopoietic Stem Cell Transplantation* / mortality
  • Hodgkin Disease / immunology
  • Hodgkin Disease / mortality
  • Hodgkin Disease / pathology
  • Hodgkin Disease / therapy*
  • Humans
  • Male
  • Middle Aged
  • Nivolumab / administration & dosage*
  • Nivolumab / adverse effects
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors*
  • Programmed Cell Death 1 Receptor / immunology
  • Progression-Free Survival
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antineoplastic Agents, Immunological
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Nivolumab