PF298 LISOCABTAGENE MARALEUCEL TREATMENT OF PATIENTS WITH RELAPSED/REFRACTORY B‐CELL NON‐HODGKIN LYMPHOMA AND SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA: INITIAL RESULTS FROM TRANSCEND NHL 001

Abstract

Background:No clinical studies have yet evaluated chimeric antigen receptor (CAR) T cell therapies in patients with relapsed/refractory (R/R) B‐cell non‐Hodgkin lymphoma (NHL) who have secondary central nervous system (CNS) lymphoma.Aims:To report data from patients with secondary CNS lymphoma receiving lisocabtagene maraleucel (liso‐cel; JCAR017), an investigational, anti‐CD19 CAR T cell product administered as a defined composition of CD4+/CD8+ CAR T cells, in the phase 1 TRANSCEND NHL 001 study.Methods:Eligible patients had confirmed B‐cell NHL with R/R disease after ≥2 prior lines of therapy. Patients with secondary CNS lymphoma were eligible as long as they also had systemic disease or, if it developed on study, patients could continue to receive liso‐cel. After lymphodepleting chemotherapy, liso‐cel was administered at 1 of 2 dose levels; 50 × 106 total CAR+ T cells (dose level 1) or 100 × 106 total CAR+ T cells (dose level 2). Efficacy was evaluated per the Lugano criteria. Patients achieving a complete response could be retreated with liso‐cel upon progressive disease.Results:At the data cutoff, 9 patients with secondary CNS lymphoma at initial treatment (n = 6), retreatment (n = 2), or cycle 2 (n = 1) received liso‐cel. Four patients were treated at dose level 1 and 5 at dose level 2. The median (range) age was 60 (47–73) years and the number of prior lines of therapy was 3 (2–7). Median (range) time to peak CAR+ T cell expansion was 12.5 (7–112) days. One of 9 patients had grade 2 cytokine release syndrome (CRS) and 1 of 9 patients had a neurological event (NE; grade 3 decreased level of consciousness). No retreatment patients had CRS or NE, however, 1 retreatment patient had an NE of grade 2 temporal edema during the initial treatment with liso‐cel. Five patients received prophylactic levetiracetam. One patient received corticosteroids and tocilizumab. Other toxicities were predominantly cytopenias. There were no treatment‐related deaths. Four patients responded to liso‐cel; all with a best response of complete response, of which 2 are ongoing at 270 and 545 days post‐liso‐cel. All 4 responses occurred after initial liso‐cel treatment; no retreated patients responded.Summary/Conclusion:In the ongoing TRANSCEND NHL 001 study, liso‐cel continues to demonstrate the ability to be safely delivered to patients with R/R B‐cell NHL, including those with secondary CNS lymphoma, a population of patients with a highly unmet medical need. No excess NE was noted in this population. This cohort continues to be evaluated.