Tisagenlecleucel for secondary CNS lymphoma, a case series.

Abstract

e19507 Background: Secondary CNS lymphoma (SCNSL) in setting of relapsed, refractory (R/R) B cell lymphoma has unmet needs as this disease state has a poor prognosis with a reported median survival of 2 to 5 months. Historically, the mainstay of treatment for SCNSL in setting of R/R B cell lymphoma included high dose methotrexate, whole brain radiation (WBRT), and/or chemotherapy followed by autologous stem cell transplant. More recently, chimeric antigen receptor (CAR)-T cell therapy has gained attention as a new modality of therapy for patients with R/R SCNSL. The first two CAR-T cell products to gain FDA approval for R/R B cell lymphoma were Axicabtagene ciloleucel and Tisagenlecleucel. In the initial studies for these products, patients with SCNSL were excluded due to concerns for immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome (CRS). Retrospective data has shown that patients with R/R SCNSL treated with Axicabtagene ciloleucel or Tisagenlecleucel could achieve high response rates; however, the data on the durability of response remains unclear. Recently, Lisocabtagene maraleucel, another CAR-T cell product, was approved for the treatment of R/R B cell lymphoma. The TRANSCEND trial which led to Lisocabtagene maraleucel’s approval did not exclude patients with SCNSL; however, only 3% of the patients had SCNSL. As such, literature on the durability of response of CAR-T cell therapy in R/R SCNSL still remains sparse. Here, we share our single institution experience of patients with R/R SCNSL treated with Tisagenlecleucel, an anti- CD19CAR-T cell therapy. Methods: For this observational study, patients with R/R SCNSL were identified and placed on a follow up list. Data was collected from May 2021 till December 2021. Data was analyzed for incidence of ICANS, CRS, and for duration of response. Results: A total of 3 patients with SCNSL were identified and treated at our center with Tisagelecleucel. One patient achieved complete response 30 days post CAR-T therapy but the day +100 imaging revealed progression of disease and was placed on subsequent line of therapy. One patient had partial response with progression of disease noted on day +60 imaging and died from complications of disease progression. One patient died from complications of CNS toxicity after receiving CAR-T therapy. Two patients had ICANS grade 4 and CRS grade 1 toxicities. One patient had no CNS or CRS toxicity. Conclusions: Our series is limited by the number of patients; however, suggests that though CAR-T therapy may result in disease response in R/R SCNSL the duration of response may be limited and that such patients may require other therapies such as autologous stem cell transplant to improve long term prognosis.