SALVAGE TREATMENTS FOR RELAPSED/REFRACTORY SECONDARY CNS LYMPHOMA IN THE CAR T ERA: A REAL‐WORLD COMPARISON

Abstract

Introduction: Secondary central nervous system lymphoma (SCNSL) is a rare and aggressive subtype of non-Hodgkin lymphoma that involves the neuraxis. Patients with refractory or relapsed (r/r) disease have limited treatment options and poor outcomes. Chimeric antigen receptor T-cell therapy (CAR T) has shown promise in clinical trials but lacks mature data in the r/r SCNSL setting. In this retrospective, real-world review, we evaluated salvage treatment patterns and survival outcomes of patients with r/r SCNSL, comparing historic regimens to CAR T. Methods: We retrospectively reviewed medical records of SCNSL patients treated at our institution between 2008 and 2022. Patients were included if they had r/r disease and received salvage treatment. Progression-free (PFS) and overall survival (OS) from initiation of first salvage therapy were calculated using the Kaplan-Meier method. Results: We identified 28 r/r SCNSL patients, 11 with de novo CNS disease and 17 with CNS relapse. Initial treatments were based on intrathecal or high-dose methotrexate. Six patients underwent consolidative autologous stem cell transplant. Upon relapse, 7 patients received supportive care with steroids only with rapid disease progression and death within one month. The remaining 21 patients had a median age of 60 years (range, 34-77 years) and median Karnofsky performance status of 80. The most common histological subtype was diffuse large B-cell lymphoma (DLBCL) (n=19, 90%). CNS disease was mostly parenchymal (52%), followed by spinal cord (29%) and leptomeningeal (19%) involvement. Salvage regimens included combinations of radiation (RT, n = 14), immunologic, targeted and chemotherapies [(rituximab, ibrutinib, polatuzumab; n = 15), methotrexate (n = 11), temozolomide (n = 8)], and CAR T (n = 7). The overall response rate was 67% for initial salvage therapy, with 9 patients having a sustained response. Median OS was 23 months and median PFS was 10 months. Seven patients who underwent salvage anti-CD19 CAR T had improved PFS and OS compared to other salvage regimens (p = 0.0014, Figure 1). Four of these patients received bridging therapy, either with RT (n = 2) or chemo-immunotherapy (n = 2). The majority (6/7) remain alive, and 4/7 patients remain in complete remission past 1.5 years. 6/7 patients had grade 1-2 CRS and 4/7 had grade 2-3 ICANS that was successfully managed per institutional guidelines. Median OS for other salvage regimens was 6.2 months. The addition of radiation to systemic therapy trended to improve OS. Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cellular therapies, Extranodal non-Hodgkin lymphoma This research was supported by the American Society of Hematology (ASH) HONORS Award. Conflicts of interests pertinent to the abstract G. Kaur Consultant or advisory role: SANOFI, BMS, Janssen, Cellectar, Arcellx Y. F. Madanat Consultant or advisory role: Sierra Oncology, Stemline Therapeutics, Blueprint Medicines, Morphosys, Taiho Oncology and Novartis. Honoraria: BluePrint Medicines, GERON, OncLive, and MD Education Travel grants: Blueprint Medicines and Morphosys P. Ramakrishnan Geethakumari Consultant or advisory role: PRG has provided consultancy services to Kite Pharma, Bristol Myers Squibb and Rafael Pharma and served on the advisory boards of Pharmacyclics LLC, ADC Therapeutics, Cellectar Biosciences and Ono Pharma.