Data Support Liso-Cel for Relapsed or Refractory CLL/SLL

Lisocabtagene maraleucel (liso-cel) is a potential treatment option for patients with relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), according to research presented at the International Conference on Malignant Lymphoma 2023.

The chimeric antigen receptor (CAR) T-cell therapy produced “rapid, deep, and durable responses” in CLL/SLL patients, said study presenter Tanya Siddiqi, MD, of City of Hope in Duarte, California.

These findings come from the phase1/2 TRANSCEND CLL 004 trial (ClinicalTrials.gov Identifier: NCT03331198). The trial enrolled adults with relapsed or refractory CLL/SLL who were ineligible for, or whose disease had progressed on, BTK inhibitor (BTKi) therapy.

A total of 117 patients underwent leukapheresis and received liso-cel. At baseline, the median age of the cohort was 65 (range, 49-82) years. Forty-four percent of patients had bulky lymphadenopathy, and 83% had high-risk cytogenetics. The patients had received a median of 5 prior lines of therapy (range, 2-12). A subset of 70 patients had disease progression on BTKi therapy as well as venetoclax failure.

Dr Siddiqi presented efficacy outcomes in 87 patients who received liso-cel at the second dose level tested — 100 x 10⁶ CAR T cells. This included 49 patients with BTKi progression and venetoclax failure.

The primary endpoint was complete response (CR) or CR with incomplete count recovery (CRi). The CR/CRi rate was 18% in the overall cohort and in patients with BTKi progression and venetoclax failure.

The overall response rate was 47% in the overall population and 43% in patients with BTKi progression and venetoclax failure. Rates of undetectable minimal residual disease (uMRD) in the blood were 64% and 63%, respectively. The rate of uMRD in the bone marrow was 59% in both patient groups.

The median duration of response was 35.3 months in all responders and among responders with BTKi progression and venetoclax failure.

In the overall cohort, the median progression-free survival (PFS) was 18.0 months overall, not reached in patients with a CR/CRi, 26.9 months in patients with a partial response (PR)/nodal PR (nPR), and 3.7 months in nonresponders.

Among patients with BTKi progression and venetoclax failure, the median PFS was 11.9 months overall, not reached in patients with a CR/CRi, 26.2 months in patients with a PR/nPR, and 3.7 months in nonresponders.

In the overall cohort, the median overall survival (OS) was 43.2 months overall, not reached in responders, and 10.7 months in nonresponders. Among patients with BTKi progression and venetoclax failure, the median OS was 30.3 months overall, not reached in responders, and 10.7 months in nonresponders.

Dr Siddiqi reported safety data in all 117 patients who received liso-cel. Most patients (85%) developed cytokine release syndrome (CRS), and 9% had grade 3 CRS. There were no cases of grade 4 or 5 CRS reported.

Neurologic adverse events (AEs) occurred in 45% of patients. The rate of grade 3-4 neurologic AEs was 19%. Other common AEs were prolonged cytopenia (54%) and grade 3 or higher infections (17%). There were 5 fatal AEs, but only 1 was considered related to liso-cel. The patient died of macrophage activation syndrome.

Dr Siddiqi concluded that these results support liso-cel as a potential new treatment option for patients with relapsed or refractory CLL/SLL.

Disclosures: This research was supported by Juno Therapeutics, a Bristol Myers Squibb company. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel (liso-cel) in R/R chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Primary analysis of TRANSCEND CLL 004. ICML 2023. June 13-17, 2023. Abstract 26.