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Severe immune-related complications early after allogeneic hematopoietic cell transplantation for nivolumab-pretreated lymphoma

Bone Marrow Transplantation volume 54, pages 473–476 (2019)Cite this article

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Immune checkpoint blockade has been increasingly used for treatment of advanced malignant lymphomas [1]. Two anti-programmed cell death 1 (PD-1) monoclonal antibodies, nivolumab and pembrolizumab, have been shown to be safe and effective for relapsed and refractory classic Hodgkin lymphoma and several types of non-Hodgkin lymphoma in large clinical trials [2,3,4,5,6].

While these novel drugs are promising as salvage treatments for relapsed/refractory lymphomas, data are limited on the safety and efficacy of PD-1 blockade before and after allogeneic hematopoietic cell transplantation (allo-HCT) [7,8,9,10,11,12]. Although PD-1 blockade could theoretically enhance the graft-versus-lymphoma effect, there is a significant concern that immune modulation with PD-1 blockers can exacerbate alloimmune toxicity. We previously reported that pre-transplant mogamulizumab therapy increased graft-versus-host disease (GVHD)-related mortality in adult T-cell leukemia/lymphoma patients [13], which might be attributed to depletion of CCR-4-expressing regulatory T cells and a subsequent decrease in post-transplant immune tolerance. In the largest retrospective study thus far, 39 patients with advanced lymphoma who had received PD-1 blockade prior to allo-HCT had a high incidence of severe GVHD, and febrile syndrome occurred in the peri-engraftment period [9]. In that report, patients who had bone marrow transplantation had a lower risk of grade III–IV acute GVHD than those who had peripheral blood stem cell transplantation (0% vs 32%). In another report that included nine cases of peripheral blood stem cell transplantation after nivolumab, all patients experienced acute GVHD, five with grade III and one with grade IV [10]. Based on these existing data, the recommendation on transplant strategies in this setting was recently published [7]. To reduce the risk of immune-related complications or GVHD, bone marrow source, reduced-intensity conditioning, post-transplant cyclophosphamide-based GVHD prophylaxis, and at least 6-week interval from the last administration to transplant are recommended in the PD-1-blocker-pretreated patients. No published data are available on cord blood transplantation.

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Authors and Affiliations

  1. Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Masatomo Kuno, Ayumu Ito, Takashi Tanaka, Yoshihiro Inamoto, Saiko Kurosawa, Sung-Won Kim & Takahiro Fukuda

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  1. Masatomo Kuno
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Correspondence to Ayumu Ito.

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Kuno, M., Ito, A., Tanaka, T. et al. Severe immune-related complications early after allogeneic hematopoietic cell transplantation for nivolumab-pretreated lymphoma. Bone Marrow Transplant 54, 473–476 (2019). https://doi.org/10.1038/s41409-018-0310-6

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