Lisocabtagene maraleucel (liso-cel) is an investigational, anti-CD19, defined composition, 4-1BB chimeric antigen receptor (CAR) T-cell product, administered at a target dose of CD4+ and CD8+ CAR T-cells. An ongoing, open-label phase 1/2 (TRANSCEND CLL 004; NCT03331198) study is evaluating liso-cel in patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL); updated results of the study were presented at the 2019 ASH meeting and are summarized here.
Eligible patients with CLL/SLL had received ≥3 (standard-risk disease) or ≥2 (high-risk disease) prior lines of therapy, including a Bruton’s tyrosine kinase inhibitor (BTKi). Following lymphodepletion (3 days) with fludarabine/cyclophosphamide, patients received liso-cel infusion (dose level [DL]1 = 50 × 106 and DL2 = 100 × 106 CAR+ T-cells). Dose-limiting toxicities (DLTs) were evaluated for 28 days postinfusion. Minimal residual disease (MRD) was assessed at a sensitivity of ≤10-4 in blood and/or bone marrow (BM) lymphocytes. Liso-cel CAR T-cells were monitored by flow cytometry of blood cells from treated patients over time. Serum cytokines and chemokines were assessed via an electrochemiluminescence platform.
In this analysis, 23 patients were evaluable for safety and 22 for efficacy. The median age among the study population was 66 years (range, 49-79); the majority (83% [19/23]) of patients had high-risk disease (del[17p], TP53 mutation, unmutated IGHV, or complex karyotype). Patients had received a median of 5 prior therapies (range, 2-11). All patients had received prior ibrutinib; 39% (9/23) had progressed on a BTKi and failed venetoclax; 91% (21/23) were R/R to ibrutinib.
Using established processes, liso-cel was successfully manufactured in 96% of patients. At DL2, 2 patients had DLTs (grade 4 hypertension in 1 patient; grade 3 encephalopathy, grade 3 muscle weakness, and grade 4 tumor lysis syndrome in 1 patient). The most common grade 3/4 treatment-emergent adverse events were thrombocytopenia (70%), anemia (78%), neutropenia (56.5%), and leukopenia (43.5%). Grade 3 cytokine release syndrome (CRS) was reported in 2 patients, and grade ≥3 neurologic events (NEs), including encephalopathy, were reported in 5 patients. The median time to first onset of CRS was 4 days (range, 1-10), and time to onset of NEs was 4 days (range, 2-21). The median duration of CRS and NEs was 12 days (range, 2-50) and 21 days (range, 6-56), respectively.
At a median follow-up of 11 months, the best overall response rate among 22 evaluable patients was 81.5%, including a complete response (CR)/CR with incomplete hematologic response rate of 45.5%. The depth of responses increased over time in 6 patients. The majority of MRD-evaluable patients (n = 20) achieved blood (15 [75%]) and/or BM (13 [65%]) undetectable (u)MRD.
The study investigators concluded that liso-cel treatment in heavily pretreated patients with R/R CLL/SLL who had failed ibrutinib was manageable and produced durable uMRD responses.
Siddiqi T, et al. ASH Abstract 503. Session 642.