Simultaneous Sessions I: Novel agents and therapies for CLL
Eradication of minimal residual disease (MRD) in patients with chronic lymphocytic leukemia (CLL) may be necessary for deep and durable responses.
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.
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 × 106) or dose level 2 (100 × 106) 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).
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.
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.