Allogeneic hematopoietic cell transplantation (allo-HCT) is an option for patients with Hodgkin’s lymphoma (HL) who relapse after autologous HCT. Recently, response rates of 87% after treatment with nivolumab (a monoclonal IgG4 anti-PD-1 antibody) in relapsed/refractory HL even after autologous HCT were published (Ansell et al., NEJM 2015). Yet, the impact of nivolumab with its immune-related mechanism of action after allo-HCT is unknown. We report the use of nivolumab after allo-HCT for relapsed HL. Patient and methods: The patient is a 52-year-old female with HL, stage IVLA in 5th relapse. Earlier treatments were standard chemotherapies prior to and after autologous HCT. In 2010, the patient received an allo-HCT from an HLA-identical unrelated donor. She developed extensive graft versus host disease (GvHD) of the skin and liver. The patient suffered further relapses and was treated with brentuximab, and gemcitabine. Immunosuppression could be discontinued in 2014. Peripherally, NK- and T-cells were 100% of donor origin. A PET-CT prior to nivolumab displayed a generalized lymph node, pulmonary and bone involvement by HL. Immunohistochemical staining of a tissue biopsy revealed that the Hodgkin- and Reed-Sternberg cells expressed the PD-L1 protein. Results Nivolumab was started (3mg/kg at week 1 and 4, and then every 2 weeks) in July, 2015. A PET-CT at week 5 revealed a complete remission which is now maintained for 8 months. Two weeks after the first infusion, an upsurge in eosinophils, NK- and T-cell populations occurred (table). CD279 (PD-1) was expressed on 21% of the T-cells. A grade 3 hepatotoxicity at week 6 necessitated an interruption of nivolumab for 5 weeks and treatment with prednisolone 25 mg QD. Nivolumab was resumed and prednisolone tapered without evidence of further immune-mediated adverse events or GvHD. Conclusion A fast and complete remission with immunologic checkpoint blockade is possible even after allo-HCT. However, a therapeutic blockade of the PD-1 pathway may influence the function of lymphocytes and NK-cells. Thus, further data are needed to establish the impact of PD-1/PD-L1 blockade after allo-HCT.
Table: Peripheral WBC counts under nivolumab.