Liso-Cel Improves Outcomes in R/R CLL/SLL Following 2 or More Lines of Therapy

Patients with chronic lymphocytic leukemia (CLL) or small lymphocytic leukemia (SLL) who relapse following treatment with a Bruton tyrosine kinase inhibitor (BTKi) and venetoclax (Venclexta; Abbvie, Genentech) have superior outcomes if they are treated with lisocabtagene maraleucel (liso-cel; Breyanzi) compared with standard-of-care therapy, a new report shows.¹

The findings were based on an analysis that compared patients from the TRANSCEND CLL 004 trial (NCT03331198) of liso-cel with a matched cohort of patients treated in a real-world setting. The data were presented at the American Society of Clinical Oncology 2025 annual meeting in Chicago.

After adjustment for imbalances, patients in the liso-cel group had an overall response rate of 52.5%, compared with 19.2% in the standard-of-care group. | Image credit: fotogurmespb- stock.adobe.com

Patients with relapsed or refractory (R/R) CLL/SLL whose cases have progressed despite treatment with BTKi’s and venetoclax have few other options and poor survival outcomes, wrote William Wierda, MD, PhD, of the University of Texas M.D. Anderson Cancer Center, and colleagues.

The TRANSCEND CLL 004 trial was a phase 1-2 study that looked at the potential of liso-cel, a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, to offer a lifeline to this hard-to-treat patient group. In results published in 2023, the study’s investigators found that the therapy sparked complete responses or remission (including incomplete marrow recovery) in a statistically significant subset of patients and also had a manageable safety profile.² Those results led the FDA to approve the therapy for certain adults with R/R CLL/SLL last year.³ 

However, Wierda and colleagues noted that the 2023 study was a single-arm trial with no comparator group.¹ The new report aimed to compare outcomes with liso-cel to outcomes in patients treated with other existing therapies. The authors assembled a matched cohort of 212 patients with R/R CLL/SLL following at least 2 prior lines of therapy who underwent standard-of-care therapy in a real-world setting upon relapse. Those patients were then compared with 66 patients from the TRANSCEND CLL 004 trial.

Patients in the standard-of-care arm were treated with a variety of therapies, including chemotherapy, non-CAR-T immunotherapy, BTKis, venetoclax, phosphatidylinositol 3-kinase inhibitors, or a combination thereof. The median follow-up for the standard-of-care arm was 17.2 months; the median follow-up for the liso-cel arm was 35.4 months.

The investigators found the liso-cel group had superior outcomes. After adjustment for imbalances, patients in the liso-cel group had an overall response rate of 52.5% (95% CI, 34.8-79.2), compared with 19.2% (95% CI, 14.1-26.1) in the standard-of-care group.

The median progression-free survival (PFS) was 12.0 months for patients in the liso-cel group (95% CI, 10.8-13.2), compared to 4.4 months for the standard-of-care group (95% CI, 3.2-5.5). When the investigators calculated probable PFS for 24 and 36 months, the rates for liso-cell were 46.3% and 30.3%, respectively, compared to 11.5% and 5.1%, respectively, for patients receiving standard of care.

In terms of overall survival (OS), the median OS in the liso-cel cohort was 33.6 months (95% CI, 31.7-35.5), compared to 14.8 months for the standard-of-care group (95% CI, 9.4-20.1). Probable OS at 24 months was 73.4% for the liso-cel group and 35.1% for the standard-of-care group. At 36 months, the probable OS was 42.6% and 29.7%, respectively.

The investigators concluded the data show liso-cel “was associated with significantly improved response, delayed progression, and prolonged survival” compared to standard of care.

References

1. Wierda W, Wang L, Liu FF, et al. Comparison of outcomes for patients (pts) with R/R chronic lymphocytic leukemia (CLL)/small lymphocytic leukemia (SLL) previously treated with Bruton tyrosine kinase inhibitor (BTKi) and venetoclax from the TRANSCEND CLL 004 study versus a matched cohort of real-world (RW) pts. Presented at: 2025 American Society of Clinical Oncology annual meeting; May 30-June 3, 2025; Chicago, Illinois. Abstract 7039.
2. Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel in chronic lymphocytic leukaemia and small lymphocytic lymphoma (TRANSCEND CLL 004): a multicentre, open-label, single-arm, phase 1-2 study. Lancet. 2023;402(10402):641-654. doi:10.1016/S0140-6736(23)01052-8
3. U.S. FDA approves Bristol Myers Squibb’s Breyanzi as the first and only CAR T-cell therapy for adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). News release. Bristol Myers Squibb. March 14, 2024. Accessed June 16, 2025. https://www.businesswire.com/news/home/20240313169337/en/U.S.-FDA-Approves-Bristol-Myers-Squibb