PB1816 NIVOLUMAB TREATMENT FOR RELAPSED AND REFRACTORY PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA AND PRIMARY TESTICULAR LYMPHOMA WITH CNS INVOLVEMENT
Authors: D. Shmidt, G. Andrey, A. Polushin, E. Kondakova, K. Lepik, Y. Zalyalov, N. Mikhailova, B. Afanasyev
Journal: HemaSphere (2019)

Background: Primary central nervous system lymphoma (PCNSL) and CNS involvement in primary testicular lymphoma (PTL) are two biologically closely related entities that carry suboptimal prognosis. Recent insights into the biology of this neoplasms provided a rationale for exploiting targeted therapy and immunotherapy. Given that these tumors express high levels of PD‐1 and PD‐1L, targeting this pathway with immune checkpoint inhibitors such as nivolumab is of particular interest. There is a little evidence regarding feasibility of checkpoint inhibitors use in these malignancies with the only paper of Nayak et al. (Blood, 2017) to be illustrative of efficacy and safety of this therapeutic modality. Here we report case series of 5 PCNSL patients and one patient with PTL with CNS involvement treated with nivolumab either in monotherapy or in combination with other agents. Aims: to report efficacy and safety of checkpoint inhibitor immunotherapy using nivolumab in patients with PCNSL and CNS involvement in PTL. Methods: 5 patients diagnosed with primary CNS DLBCL and 1 patient diagnosed with PTL with CNS involvement were treated in First Pavlov State Medical University of Saint‐Petersburg between January 2017 and February 2019. Median age at a diagnosis was 55 (30‐65) years. Median age at the start of treatment with nivolumab was 56 (33‐66) years. At the treatment initiation, median Karnofsky performance status (KPS) was 70 (40‐90) and Eastern Cooperative Oncology Group (ECOG) status – 1,5 (1‐3). Four pts had multifocal lesions and 3 had involvement of deep structures (basal ganglia, brainstem and cerebellum). All patients had brain parenchyma disease and no ocular involvement. One patient had leptomeningeal disease as well. Nivolumab was used as first‐line therapy in one patient with poor performance status who was not candidate for methotrexate (MTX)‐based regimen. In the rest patients, nivolumab was used in relapsed/refractory setting with 1 to 6 previous therapy lines. Three patients received nivolumab as monotherapy and 3 in combination with other agents (rituximab in 1 case, high‐dose MTX with cytarabine and rituximab in the other, and ibrutinib in case of PTL patient). Nivolumab dosing were as follows: 3 pts – 3 mg/kg, 3 pts – 100 mg regardless of body weight. Response to treatment was assessed according to standardized guidelines for response assessment in PCNSL (Abrey et al., 2005). Results: At the time of analysis, median follow‐up was 7,5 (0,5‐24) months. In all patients the treatment was well tolerated with no reported immune related adverse events. Among patients with assessed response 2 pts achieved a complete response (CR), 1 patient had stable disease as best response to the treatment and 2 pts experienced progression. Later, one patient with PCNSL relapsed after CR. Retreatment with nivolumab, rituximab and intrathecal MTX, cytarabine, dexamethasone allowed to obtain CR again. Median progression‐free survival was 7 months (0,5‐24) with 4 pts still alive at the time of analysis. Summary/Conclusion: Nivolumab containing regimens may be efficient treatment option in patients with relapsed/refractory primary CNS lymphoma and primary testicular lymphoma or in patients who are not candidates for standard intensive chemotherapy regimen. The place of nivolumab in the treatment of PCNSL and PTL should be further determined in prospective clinical trials.