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Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 51, pages 850–852 (2016)Cite this article

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The immunotherapeutic contribution to allogeneic stem cell transplantation's (SCT’s) curative potential in hematological diseases is well recognized, with alloreactive donor T and NK lymphocytes mediating a graft-versus-tumor (GVT) effect.1 Recent advances in our understanding of immune regulatory pathways have identified immune check-point exploitation by cancer cells in the tumor microenvironment as a ‘druggable’ mechanism of immune evasion. The programmed death-1 (PD-1) regulatory pathway is active in several tumors and a potent immunotherapeutic target, with PD-1 inhibitors eliciting antitumor responses.2, 3, 4 Nivolumab, an anti-PD-1 monoclonal antibody (Ab), is approved therapy for melanoma5 and non-small squamous cell lung cancer;6 it also exhibits robust clinical activity in refractory/relapsed Hodgkin lymphoma (HL).7 Although PD-1 inhibition may effectively unleash GVT responses in relapsed HL after allogeneic SCT, the risks of graft-versus-host disease (GvHD)or graft rejection are unknown. We report herein the effective and safe use of nivolumab in a patient with relapsed/refractory HL progression after allogeneic SCT.

Our patient exhibited a limited GVT effect after allogeneic SCT, with disease progression and no evidence of GvHD. Following treatment with nivolumab, a major clinical response was observed in her highly refractory HL. It is reassuring that her response, presumably immune mediated by donor tumor-infiltrating lymphocytes, could be achieved without GvHD or graft rejection. In HL, constitutive PD-L1/PD-L2 expression in HRS cells8 may render them exquisitely sensitive to disruption of the PD-1 pathway, accounting for a tumor-specific immune response. Although PD-1 has been implicated in regulating alloreactivity, our patient appears to have maintained allogeneic tolerance. Grade 2 pneumonitis and hepatitis responded to corticosteroid therapy, and subsequent administration with dose escalation has been well tolerated thus far. The durability of this response remains to be seen and thus the optimal duration of therapy is unclear. Nonetheless, this first reported case suggests that immunotherapy targeting PD-1 may be safe and effective in patients with HL progression after allogeneic SCT and warrants prospective study.

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Authors and Affiliations

  1. Division of Hematology/Oncology, Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    J A Yared, N Hardy, A Z Badros, M Kocoglu, S Yanovich, E A Sausville, K Ruehle, C Goecke, M Landau & A P Rapoport

  2. Department of Pathology, University of Maryland, Baltimore, MD, USA

    Z Singh

  3. Department of Diagnostic Radiology and Nuclear Medicine, University of Maryland, Baltimore, MD, USA

    S Hajj

  4. Division of Hematology/Oncology, Lombardi Cancer Center, Georgetown University, Washington DC, WA, USA

    C Ujjani

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  1. J A Yared
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  2. N Hardy
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  3. Z Singh
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  5. A Z Badros
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  8. E A Sausville
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  9. C Ujjani
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  10. K Ruehle
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  12. M Landau
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  13. A P Rapoport
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Correspondence to J A Yared.

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Yared, J., Hardy, N., Singh, Z. et al. Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant 51, 850–852 (2016). https://doi.org/10.1038/bmt.2015.346

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