Liso-Cel Therapy Demonstrates Enhanced Efficacy in R/R CLL/SLL Patients

In a significant advancement for the treatment of relapsed or refractory chronic lymphocytic leukemia (R/R CLL) and small lymphocytic lymphoma (SLL), new data presented at the 2025 American Society of Clinical Oncology (ASCO) annual meeting reveals that lisocabtagene maraleucel (liso-cel), a chimeric antigen receptor (CAR) T-cell therapy, substantially improves patient outcomes compared to standard therapies. The findings, derived from a comparative analysis of the TRANSCEND CLL 004 trial and a matched real-world cohort, indicate enhanced response rates and survival metrics for patients receiving liso-cel.

The study, conducted by a team led by Dr. William Wierda of the University of Texas M.D. Anderson Cancer Center, involved a cohort of 66 patients from the TRANSCEND CLL 004 trial and 212 patients from a real-world setting who had undergone at least two prior lines of therapy. The results highlighted a striking overall response rate of 52.5% for the liso-cel group, in stark contrast to just 19.2% for those receiving standard-of-care treatments, which included chemotherapies, Bruton tyrosine kinase inhibitors (BTKis), and venetoclax.

The median progression-free survival (PFS) was also significantly better for the liso-cel cohort, with a median PFS of 12.0 months compared to 4.4 months for the standard therapy group. Furthermore, the median overall survival (OS) for patients treated with liso-cel was reported at 33.6 months, a considerable improvement over the 14.8 months observed in the standard treatment cohort.

According to Dr. Wierda, “The data clearly demonstrate that liso-cel not only improves response rates but also delays disease progression and extends overall survival in a patient population that has historically faced poor outcomes.” This study marks an important step in validating CAR T-cell therapy's role in managing R/R CLL/SLL, particularly among patients who have experienced treatment failures with existing therapies.

The results align with earlier findings from the TRANSCEND CLL 004 trial, which had already established liso-cel’s potential in delivering complete responses among a subset of patients. However, previous results lacked a comparative group, making this new analysis vital for contextualizing liso-cel’s efficacy against traditional treatments.

The therapeutic landscape for R/R CLL/SLL has been evolving, with the FDA's approval of liso-cel in March 2024 as the first CAR T-cell therapy specifically for adults with these conditions. This approval followed the promising outcomes outlined in the earlier trial results published in the Lancet in 2023.

The implications of these findings are profound, as they not only highlight the potential of liso-cel to reshape treatment protocols for R/R CLL/SLL but also provide hope for patients who have exhausted available therapies. The ongoing challenge remains in identifying suitable candidates for such advanced therapies, as well as managing the associated costs of CAR T-cell treatments.

As the oncology community continues to assess the long-term impacts of liso-cel therapy, further studies are warranted to elucidate the full potential of CAR T-cells in various hematological malignancies. The future of R/R CLL/SLL treatment may be increasingly defined by personalized approaches that leverage innovative therapies like liso-cel, ultimately aiming to improve patient survival and quality of life.