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Association between GvHD and nivolumab in the FDA adverse event reporting system

Bone Marrow Transplantation volume 52, pages 1463–1464 (2017)Cite this article

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The US Food and Drug Administration (FDA) approved nivolumab for treatment of relapsed or refractory classical Hodgkin’s lymphoma (HL) in May 2016. Nivolumab is supposed to inhibit immune checkpoint programmed cell death 1 (PD-1) and to release the brakes on tumor-suppressed lymphocytes.1 In patients treated with allogeneic hematopoietic stem cell transplantation (allo-HSCT), GvHD could be unleashed through the same mechanism theoretically. Several recent reports have assessed the possible association between nivolumab and the onset of GvHD for patients treated with allo-HSCT.2, 3, 4, 5, 6 In May 2016, the US FDA made an amendment of the warning and precaution in the prescriber’s information concerning complications of allo-HSCT that patients should be followed for hyperacute GvHD, severe acute GvHD, steroid-requiring febrile syndrome, hepatic veno-occlusive disease and other immune-mediated adverse reactions. However, no comparative study with or without nivolumab that assessed the link has published so far. To examine the association between nivolumab and GvHD, we performed a comparative study using the FDA Adverse Event Reporting System (FAERS).

The FAERS database was searched using the webpage of the Pharmapendium (https://www.pharmapendium.com) in February 2017. Institutional review board approval was not required because the FAERS is an unlinkable anonymized database open to the public. We extracted reports registered between November 1997 and September 2016 for drugs approved for HL; 19 drugs were searched including bleomycin, brentuximab vedotin, carmustine, chlorambucil, cyclophosphamide, dacarbazine, doxorubicin, liposomal doxorubicin, tositumomab, lomustine, mechlorethamine, mercaptopurine, methacycline, nivolumab, procarbazine, thiotepa, triethylene melamine, vinblastine and vincristine. Among them, we further extracted the subjects whose indications of a primary suspected drug for an adverse event were HL. The data were analyzed using R software (version 3.1.2; R Development Core Team, Vienna, Austria).

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References

  1. Armand P . Immune checkpoint blockade in hematologic malignancies. Blood 2015; 125: 3393–3400.

    Article  CAS  PubMed  Google Scholar 

  2. Angenendt L, Schliemann C, Lutz M, Rebber E, Schulze AB, Weckesser M et al. Nivolumab in a patient with refractory Hodgkin’s lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant 2016; 51: 443–445.

    Article  CAS  PubMed  Google Scholar 

  3. Haverkos BM, Schowinksy J, Kaplan J, Kamdar M, Kanate AS, Saad A et al. Checkpoint blockade for treatment of relapsed lymphoma following allogeneic hematopoietic cell transplant: use may be complicated by onset of severe acute graft versus host disease. Blood 2016; 128: 22 (abstract 1163).

    Google Scholar 

  4. Schoch LK, Borrello I, Fuchs EJ, Bolanos-Meade J, Huo JS, Gojo I et al. Checkpoint inhibitor therapy and graft versus host disease in allogeneic bone marrow transplant recipients of haploidentical and matched products with post transplant cyclophosphamide. Blood 2016; 128: 22 (abstract 4571).

    Google Scholar 

  5. Herbaux C, Gauthier J, Brice P, Drumez E, Ysebaert L, Doyen H et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin’s lymphoma. Blood 2017; 129: 2471–2478.

    Article  CAS  PubMed  Google Scholar 

  6. Merryman RW, Kim HT, Zinzani PL, Carlo-Stella C, Ansell SM, Perales M-A et al. Safety and efficacy of allogeneic hematopoietic stem cell transplant after PD-1 blockade in relapsed/refractory lymphoma. Blood 2017; 129: 1380–1388.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Blazar BR, Carreno BM, Panoskaltsis-Mortari A, Carter L, Iwai Y, Yagita H et al. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an INF-gamma-dependent mechanism. J Immunol 2003; 171: 1272–1277.

    Article  CAS  Google Scholar 

  8. Saha A, Aoyama K, Taylor PA, Koehn BH, Veenstra RG, Panoskaltsis-Mortari A et al. Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood 2013; 122: 3062–3073.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Ni X, Song Q, Cassady K, Deng R, Jin H, Zhang M et al. PD-L1 interacts with CD80 to regulate graft-versus-leukemia activity of donor CD8+ T cells. J Clin Invest 2017; 127: 1960–1977.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Fuji S, Shindo T . Friend or foe? Mogamulizumab in allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia/lymphoma. Stem Cell Investig 2016; 3: 70–77.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

Author contributions

YO analyzed data, drafted the paper and contributed analytical tools; TT designed research and wrote the paper; KY performed research and analyzed data; and AT designed research.

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Authors and Affiliations

  1. The Institute of Medical Science, The University of Tokyo, Tokyo, Japan

    Y Oshima, K Yuji & A Tojo

  2. Jyoban Hospital of Tokiwa Foundation, Fukushima, Japan

    T Tanimoto

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  1. Y Oshima
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  2. T Tanimoto
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  3. K Yuji
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Correspondence to Y Oshima.

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Competing interests

YO reports personal fees from Novartis Pharma KK and Sanofi KK, outside the submitted work; AT reports grants from Bristol-Myers, Pfizer, Chugai Pharmaceutical, Daiichi Sankyo and Sumitomo Dainippon-Pharma, and personal fees from Taiho Pharmaceutical, Rohto Pharmaceutical, Celgene, Novartis, Ohtsuka Pharmaceutical and Sysmex, outside the submitted work; TT and KY declare no conflict of interest.

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Oshima, Y., Tanimoto, T., Yuji, K. et al. Association between GvHD and nivolumab in the FDA adverse event reporting system. Bone Marrow Transplant 52, 1463–1464 (2017). https://doi.org/10.1038/bmt.2017.158

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