According to results published in Blood, the autologous CD19-directed chimeric antigen receptor (CAR) T-cell therapy lisocabtagene maraleucel (liso-cel) was successfully manufactured for patients with relapsed/refractory (R/R) chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) and was associated with manageable toxicities and rapid and deep responses.

Researchers reported the results from the phase 1 dose-escalation portion of the multicenter, open-label, phase 1/2 TRANSCEND CLL 004 study of liso-cel in patients with R/R CLL/SLL ( Identifier: NCT03331198).

Adult patients (≥18 years of age) with standard- or high-risk features treated with ≥3 or ≥2 prior therapies, respectively, were administered liso-cel at a dose level 50 × 106 (DL1) or 100 × 106 CAR+ T cells (DL2). The primary objectives of the study were to evaluate safety and determine the recommended dose for the subsequent phase 2 expansion cohort. Exploratory endpoints included antitumor activity (2018 International Workshop on CLL guidelines) and minimal residual disease (MRD) in blood and marrow.

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A total of 23 enrolled patients received liso-cel and were evaluable for safety. Patients had a median age of 66 years (range, 50-80) and a median of 4 (range, 2-11) prior therapies (ibrutinib, 100%; venetoclax, 65%). High-risk features, including mutated TP53 and del(17p), were present in 83% of patients.

The researchers reported that safety was similar between dose levels. Overall, 74% of patients experienced cytokine release syndrome (grade 3, 9%) and 39% experienced neurological events (grade 3/4, 22%). They did not observe dose limiting toxicities (DLTs) in patients who received DL1 and reported DLTs at DL2 in 2 patients (grade 4 hypertension, n=1; grade 3 encephalopathy, grade 3 muscle weakness, and grade 4 tumor lysis syndrome, n=1); the DLTs completely resolved.

The team also reported similar efficacy between the dose levels. Efficacy was evaluable in 22 patients. Among efficacy-evaluable patients, 82% and 45% achieved overall and complete responses, respectively. Among 20 patients who were evaluable for MRD, 75% and 65% achieved undetectable MRD in blood and marrow, respectively. In consultation with a safety review committee, DL2 (100 × 106 CAR+ T cells) was selected for the ongoing phase 2 portion of the study.

“Rapid and deep responses were observed after a single dose of liso-cel. Longer follow-up in a larger number of patients is needed to determine the durability of responses and the role of [undetectable] MRD in sustaining responses” the researchers concluded. “The ongoing phase 2 monotherapy expansion cohort, currently enrolling at DL2, will provide additional information on the safety and efficacy of liso-cel in patients with relapsed/refractory CLL/SLL.”

Limitations of the study included the single-arm design, small study sample size, and limited follow-up.

Disclosure: This research was supported by Juno Therapeutics, a Bristol-Myers Squibb Company. Please see the original reference for a full list of disclosures.


Siddiqi T, Soumerai JD, Dorritie KA, et al. Phase 1 TRANSCEND CLL 004 study of lisocabtagene maraleucel in patients with relapsed/refractory CLL or SLL. Blood. 2022;139(12):1794-1806. doi:10.1182/blood.2021011895

This article originally appeared on Hematology Advisor