There is an unmet clinical need for treatment options following progression on Bruton tyrosine kinase inhibitor (BTKi) and venetoclax treatment for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL).1 The phase 1/2, single-arm, multicenter TRANSCEND CLL 004 (NCT03331198) study is investigating the autologous, CD19-directed, 4-1BB CAR T cell product, lisocabtagene maraleucel (liso-cel) in patients with R/R CLL/SLL; primary analysis of the trial demonstrated favorable efficacy and safety outcomes, including in those patients with progression on previous BTKi and venetoclax failure.2 Extended follow-up (at median follow-up of 23.5 months) data of the TRANSCEND CLL 004 trial were presented at the 2023 American Society of Hematology annual meeting and summarized here.
TRANSCEND CLL 004 trial enrolled patients who had received ≥2 prior lines of therapy, including a BTKi. Eligible patients received liso-cel at a target dose of either 50 × 106 (dose level [DL] 1) or 100 × 106 (DL2) CAR+ T cells after lymphodepleting chemotherapy.3 The primary end point was complete response (CR)/CR with incomplete marrow recovery (CRi) at DL2. Key secondary endpoints were overall response rate (ORR) and rate of undetectable minimal residual disease (uMRD; 10−4) in blood. Data cutoff date was February 28, 2023.3
A total of 137 eligible patients underwent leukapheresis; of these, 118 received liso-cel (safety set), 97 patients (DL1=9; DL2=88) were evaluable for efficacy, and 54 (DL1=4; DL2=50) were included in the primary efficacy analysis set.3 Median age of the safety set (n=118) was 65 years; the majority (83%) had high-risk cytogenetics (del[17p]: 42%; TP53 mutation: 47%; unmuted immunoglobulin heavy-chain variable gene: 47%; ≥3 chromosomal aberrations: 61%).3 In this heavily pretreated cohort, patients had received a median of 5 lines of prior therapy; all patients had received prior BTKi.3
In the primary efficacy analysis set at DL2 (n=50), patients achieved a CR/CRi rate of 20% for an independent review committee (IRC)-assessed ORR of 44%. The uMRD rate was 64% in blood and 60% in marrow; median duration of response was 35.3 months and median duration of CR/CRi was not reported.3 The median time to next therapy was 12.4 months.3 Median progression-free survival was 11.9 months, and median overall survival was 30.3 months.3 CR/CRi were achieved by 8 of 9 patients who achieved a best overall response (BOR) in the primary analysis. In the full population at DL2 (n=88), results were similar to the primary efficacy analysis set; patients achieved a CR/Cri rate of 19% with an ORR of 48%.3
In the safety set (n=118), rates of treatment-emergent adverse events (TEAEs; both any-grade and grade ≥3) were similar across age groups. Cytokine release syndrome (CRS) was reported in 85% (any grade) of patients; of these, grade 3 were 8%; there were no grade 4/5 events.3 Neurological events occurred in 45% of patients; grade 3 were 18%, grade 4 were 1%, and no grade 5 events.3 For management of CRS and neurological events, the majority of patients (69%) were treated with tocilizumab and/or corticosteroid.3 Median time to resolution was 6 days for CRS and 7 days for neurological events, respectively.3 Other common grade ≥3 TEAEs included prolonged cytopenia, infections, hypogammaglobulinemia, tumor lysis syndrome, second primary malignancy, and macrophage activation syndrome.3
Based on these longer follow-up data, liso-cel continued to demonstrate durable CR/CRi and high uMRD rates in patients with heavily pretreated, high-risk R/R CLL/SLL; no new safety signals emerged.
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