Counterproductive effects of Daratumumab and checkpoint inhibitor for the treatment of patients with relapsing NK/T lymphoma
Lee, W.; Jinquan, L.; Tang, T. P.; Tan, D.; Kia Joo, P.; Kim Peng, T.; Liangwei, W.; Ser Mei, K.; Choon Kiat, O.; Rotzschke, O.
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Natural killer/T cell lymphoma (NK/T L) is an aggressive malignancy associated with poor prognosis in relapsed patients. Although L-asparaginase based treatments are recommended as first-line treatment in relapsed patients, advances in immunotherapies such as checkpoint inhibitions have provided new therapeutic alternatives. However, as clinical outcomes for checkpoint inhibitors seemed to vary between NK/T L patients, combination therapies have been suggested to improve treatment efficacy. Here, we compared the effects of Daratumumab (anti-CD38)/anti-PD-1 combination therapy versus anti-PD-1 monotherapy on two relapsed NK/T L patients. Anti-PD-1 triggered an upregulation of CD38 on activated T cells, leading to depletion by Daratumumab. Concomittantly, EBV-specific antibody titer was also reduced alongside with depletion of CD38+ B cells and antibody-producing plasmablasts. Taken together, combining anti-CD38 and anti-PD-1 is likely to be antithetic.
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