Nivolumab-based immunotherapy in relapsed/refractory b-cell lymphoma, unclassifiable, with features intermediate between diffuse large b-cell lymphoma and classical hodgkin lymphoma

Abstract

The treatment of relapsed/refractory gray zone lymphoma (r/r GZL) remains challenging. Genetic aberrations involving 9p24.1 and associated with programmed death ligand (PD-L1/L2) upregulation are important in GZL pathogenesis and immune evasion. Immune checkpoint inhibitor nivolumab (PD-1-blocking anti-body) may be an attractive treatment strategy in GZL. We have retrospectively assessed efficacy and toxicity of nivolumab-based regimens in nine patients with r/r GZL. Most of the patients n=7 (78%) had primary chemoresistance and the median number of prior therapy lines was 3 (range, 2-5). At the start of nivolumab treatment disease stage III-IV was in n=6 (67%) patients and bulky disease was in n=3 (33%) patients. All nine patients had high-level of PD-L1 expression (80%-100%) on tumor cells. In this group n=4 (44%) patients received nivolumab as monotherapy, n=3 (33%) received nivolumab in combination with chemotherapy, n=1 (11%) received nivolumab in combination with BV and n=1 (11%) received nivolumab in combination with lenalidomide. The objective response rate among all treated patients was 89% with 6 cases (67%) of complete response and 2 (22%), with partial response. One patient (11%) had stabilization of the disease as best response. Median duration of response was 14 (range 5-26) months. Median follow‐up time was 25 months (range, 6-30) from the start of nivolumab-based treatment. Overall survival and progression free survival rates were 83% and 38%, respectively. This case series demonstrated that nivolumab-based regimen may be an effective treatment option for patients with r/r GZL.