S109 TRANSCEND CLL 004: MINIMAL RESIDUAL DISEASE NEGATIVE RESPONSES AFTER LISOCABTAGENE MARALEUCEL (LISO‐CEL) IN PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA OR SMALL LYMPHOCYTIC LYMPHOMA

Background: Eradication of minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL) may be necessary for deep and durable responses. Aims: To assess the safety, pharmacokinetics, and efficacy of lisocabtagene maraleucel (liso‐cel, JCAR017), an investigational, anti‐CD19 chimeric antigen receptor (CAR) T cell product administered as a defined composition of CD4+/CD8+ CAR T cells, in the ongoing phase 1/2 TRANSCEND CLL 004 study. Methods: Eligible patients had CLL or small lymphocytic lymphoma (SLL), had received ≥2 prior lines of therapy (including Bruton's tyrosine kinase inhibitors [BTKi] unless medically contraindicated), and had an Eastern Cooperative Oncology Group performance status of ≤1. After 3 days of lymphodepleting chemotherapy, patients received liso‐cel infusion at either dose level 1 (50 × 10 6 ) or dose level 2 (100 × 10 6 ) total CAR+ T cells. Patients were monitored for dose‐limiting toxicities. Response was assessed by International Workshop on CLL 2008 criteria. MRD was assessed by flow cytometry in blood (sensitivity, 10 −4 ) and by Next‐Generation Sequencing in bone marrow (BM; sensitivity, 10 −6 ). Results: At data cutoff, 16 patients received liso‐cel: n = 6 in dose level 1 and n = 10 in dose level 2. Of the patients, 75% had high‐risk features ( TP53 mutation, complex karyotype, or del17p); 100% had received prior ibrutinib and 50% had received prior venetoclax. Median (range) number of prior lines of therapy was 4.5 (2‐11). There was 1 dose‐limiting toxicity of grade 4 hypertension at dose level 2. The most common grade 3/4 treatment‐emergent adverse events were cytopenias (thrombocytopenia, 75%; anemia, 69%; neutropenia, 63%; leukopenia, 56%). One patient had grade 3 cytokine release syndrome (CRS); 3 patients had grade 3 neurological events (NE). Best overall response rate (ORR) in 15 evaluable patients was 87% (13/15). Seven patients (47%) achieved complete remission with/without complete blood count recovery (CR/CRi). ORR at 6 mo was 83% (5/6). Undetectable MRD (uMRD) in blood was achieved in 10/15 patients (67%) by day 30, and in BM in 7/8 patients (88%). MRD‐negative CRs were seen in patients who had failed both BTKi and venetoclax. Median (range) time to peak blood CAR+ T cell level was 16 (4–30) days. Summary/Conclusion: In this study of heavily pretreated patients with standard‐ and high‐risk CLL/SLL and previous ibrutinib treatment, liso‐cel‐related toxicities (ie, CRS and NEs) were manageable. Patients rapidly achieved CR/CRi and uMRD. The phase 2 component of the study is currently enrolling patients for treatment at dose level 2. Additional follow‐up will be presented.