Lisocabtagene maraleucel (liso-cel) as first-line (1L) therapy for transplant-ineligible patients (pt) with primary central nervous system lymphoma (PCNSL): The CAROLYN study.

Abstract

TPS7097 Background: Treatment of PCNSL is based on high-dose methotrexate (HD-MTX) induction chemotherapy, followed by consolidative autologous stem cell transplantation (ASCT) in eligible pts. Those deemed transplant ineligible have a high risk of relapse and are a population with a significant unmet therapeutic need. Liso-cel, an autologous, CD19-directed chimeric antigen receptor (CAR) T cell product, demonstrated promising results in secondary CNS lymphoma. In a phase 2 study (NCT03484702), 4 of 5 pts with PCNSL treated with liso-cel after failure of 1L high-dose chemotherapy and ASCT achieved a CR. Here, we report the study design of the CAROLYN study (NCT07015242; currently enrolling), which is evaluating efficacy and safety of liso-cel as 1L therapy in transplant-ineligible pts with PCNSL. Methods: This open-label, single-arm, multicenter, phase 2 study will enroll approximately 65 pts. The primary endpoint is investigator-determined 12-month PFS rate (from infusion date). Secondary endpoints include additional efficacy assessments (PFS, event-free survival, and OS from enrollment; CR rate, ORR, and duration of response), safety (AEs, serious AEs, and AEs of special interest), and health-related quality of life. Key inclusion criteria are newly diagnosed PCNSL confirmed by local pathology, receipt of ≥ 2 cycles of standard-of-care regimens, transplant ineligibility (defined by investigator assessment and either age ≥ 65 years or hematopoietic stem cell transplantation-specific comorbidity index score ≥ 3), MTX-sensitive disease (CR or PR), and ECOG PS ≤ 2. Key exclusion criteria include diagnosis of secondary CNS lymphoma, primary intraocular lymphoma, primary vitreoretinal lymphoma, and isolated cerebrospinal fluid involvement. Enrolled pts can receive optional holding therapy with a HD-MTX–based regimen while awaiting leukapheresis. After leukapheresis, bridging therapy with a HD-MTX–based regimen is permitted during liso-cel manufacturing. Before liso-cel infusion, pts receive lymphodepleting chemotherapy consisting of fludarabine (30 mg/m 2 /day for 3 days) and cyclophosphamide (300 mg/m 2 /day for 3 days). Pts then receive a single infusion of liso-cel at a target dose of 100 × 10 6 CAR + T cells. After infusion, pts remain in the treatment period for 90 days and then transition to follow-up for 2 years from enrollment. The total study duration is expected to be 3 years; pts who receive liso-cel can enroll in a separate 15-year long-term follow-up (NCT03435796). Clinical trial information: NCT07015242 .