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Severe pembrolizumab-associated neutropenia after CD34+ selected allogeneic hematopoietic-cell transplantation for multiple myeloma

Bone Marrow Transplantation volume 53, pages 1065–1068 (2018)Cite this article

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Despite the advent of new effective therapies for multiple myeloma (MM), treatment of patients with relapsed/refractory myeloma (RRMM) remains challenging. Median survival is particularly poor if patients develop resistance to ImiDs or proteasome inhibitors, with a clinical course often characterized by poor responses, early relapses, and a rapid march through numerous lines of therapy [1]. Allogeneic hematopoietic-cell transplant (alloHCT) is the only curative treatment for MM, and although historically high rates of non-relapse mortality (NRM) are improving, relapse remains an important challenge. Using CD34+ selected (ex vivo T-cell depleted) allografts in RRMM patients, our institution has reported 1-year NRM of 18% and low rates of acute and chronic graft versus host disease (2% and 0%, respectively), but with modest 2-year progression-free survival (PFS) of 31% and a median PFS duration of 13.5 months [2]. This highlights a need for improved strategies in this challenging population.

Checkpoint inhibitors have demonstrated efficacy in solid and hematologic malignancies [1]. While studies of these agents were recently put on hold by the FDA due to unexpected toxicity, preliminary data has shown response rates of 50–60% and median response durations exceeding 14 months with the combination of pembrolizumab, dexamethasone, and lenalidomide, or pomalidomide [3, 4]. With increasingly widespread experience with checkpoint inhibitors, their association with immune-mediated adverse events has also become well established and has contributed to our understanding of their biological behavior [5]. Here we describe a case in which pembrolizumab used for relapse prevention after alloHCT in a patient with MM was associated with immune-mediated neutropenia. This case is unique for the severity and refractoriness of the neutropenia observed, for the alloreactive host-versus-graft etiology of the toxicity, and in that it was observed in a recipient of an ex vivo T-cell depleted allograft.

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Acknowledgements

This research was supported in part by National Institutes of Health award numbers P01 CA23766 and NIH/NCI Cancer Center Support Grant P30 CA008748. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. A.B. was supported in part by The Ottawa Hospital Department of Medicine Post Graduate Medical Educational Grant and by The Ottawa Hospital Research Institute Cushing Fellowship Award.

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Authors and Affiliations

  1. Department of Medicine, Adult Bone Marrow Transplant Service, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA

    Adam R Bryant, Miguel-Angel Perales, Roni Tamari, Jonathan U Peled & Sergio Giralt

  2. Department of Medicine, Weill Cornell Medical College, New York, NY, 10065, USA

    Miguel-Angel Perales, Roni Tamari, Jonathan U Peled & Sergio Giralt

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Correspondence to Adam R Bryant.

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M.-A.P. has received consulting fees from Merck, Incyte, and Seattle Genetics, and research support from Incyte. J.U.P. has received research support and licensing fees from Seres Therapeutics. The remaining authors declare that they have no conflict of interest.

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Bryant, A.R., Perales, MA., Tamari, R. et al. Severe pembrolizumab-associated neutropenia after CD34+ selected allogeneic hematopoietic-cell transplantation for multiple myeloma. Bone Marrow Transplant 53, 1065–1068 (2018). https://doi.org/10.1038/s41409-018-0142-4

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