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Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin's lymphoma

Charles Herbaux, Jordan Gauthier, Pauline Brice, Elodie Drumez, Loic Ysebaert, Hélène Doyen, Luc Fornecker, Krimo Bouabdallah, Guillaume Manson, Hervé Ghesquières, Reza Tabrizi, Eric Hermet, Julien Lazarovici, Anne Thiebaut-Bertrand, Adrien Chauchet, Hélène Demarquette, Eileen Boyle, Roch Houot, Ibrahim Yakoub-Agha and Franck Morschhauser

Key points

  • PD-1 blockade with nivolumab provides durable disease control after allo-HCT.

  • PD-1 blockade with nivolumab after allo-HCT is associated with 30% acute GVHD.

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is indicated for patients with relapsed and refractory Hodgkin lymphoma (HL). While long-term disease control can be achieved, relapse remains frequent. The programmed death 1 (PD-1) blocking antibody nivolumab has shown substantial therapeutic activity and an acceptable safety profile in relapsed and refractory HL who did not receive allo-HCT. However, PD-1-blocking strategy can increase the risk of Graft Versus Host Disease (GVHD) in murine models. We retrospectively assessed the efficacy and toxicity of nivolumab as a single agent in 20 HL patients relapsing after allo-HCT. GVHD occurred in six patients (30%) after nivolumab initiation. All six patients had prior history of acute GVHD. These nivolumab-induced GVHD were managed by standard treatment of acute GVHD. Two patients died of GVHD, one of progressive disease and one of the complications related to a second allo-HCT. Overall response rate was 95%. At a median follow-up of 370 days, one-year progression-free and overall survival rates were 58.2% [95%CI, 33.1 - 76.7] and 78.7% [95%CI, 52.4 - 91.5], respectively. Among 13 patients still in response, six received a single dose of nivolumab and seven remain on nivolumab. Compared to standard options in this indication, our results show that nivolumab is effective with an acceptable safety profile.

  • Submitted November 14, 2016.
  • Accepted February 24, 2017.