Dr Kenderian on Moving Liso-Cel to the First Line of CLL Treatment

Saad J. Kenderian, MB, CHB, consultant, Division of Hematology, Department of Internal Medicine, Department of Immunology, Department of Molecular Medicine, assistant professor, oncology, immunology, medicine, Mayo Clinic, discusses ongoing research taking place to potentially move lisocabtagene maraleucel (liso-cel; Breyanzi) into earlier lines of therapy for patients with chonic lymphocytic leukemia (CLL), highlighting planned and ongoing research efforts to further investigate liso-cel.

Investigating the potential transition of liso-cel into earlier lines of therapy for patients with CLL holds significant merit, Kenderian begins, saying that CLL is characterized by immune suppression, with patients exhibiting intrinsic T-cell defects that worsen over time. The progressive accumulation of these defects heightens the likelihood of T-cell dysfunction, he states. Administering CAR T-cell therapy at an earlier stage of disease presents a greater opportunity for efficacy, akin to observations in lymphoma where second-line CAR T-cell therapies yield higher response rates compared with third-line treatments, Kenderian explains. This trend is expected to be more pronounced in CLL, given the heightened dysfunctionality of CLL T cells, according to Kenderian. The continuation of ongoing or planned studies in the second-line setting is crucial, as these randomized trials compare CAR T-cell therapy against second-line therapies, Kenderian notes.

Efforts to delve deeper into the effectiveness of liso-cel and other CAR T-cell therapies in CLL are continuously evolving, he expands. Researchers are actively exploring the underlying reasons behind the diminished efficacy of CAR T-cell therapies in CLL, largely attributed to tumor microenvironment–mediated resistance mechanisms, Kenderian says. Strategies to engineer CAR T-cell therapies capable of overcoming or evading such inhibition are under exploration, representing a promising avenue of research, Kenderian elucidates.

Furthermore, within the CAR T-cell domain, there is growing recognition of the potential for combination therapies involving FDA-approved agents to enhance the efficacy of CAR T-cell therapy, he continues. Early findings from trials combining ibrutinib (Imbruvica) with CAR T-cell therapy in patients with CLL have been promising, marked by elevated response rates and reduced toxicity levels. The emergence of next-generation therapeutics within CLL further fuels optimism and underscores the dynamic nature of research aimed at optimizing treatment strategies for patients with CLL, Kenderian concludes.