Dr Kenderian on the Efficacy of Liso-Cel in R/R CLL/SLL

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 the safety and efficacy findings derived from the phase 1/2 TRANSCEND CLL 004 study (NCT03331198) evaluating lisocabtagene maraleucel (liso-cel; Breyanzi) in patients with relapsed/refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

for the treatment of adult patients with relapsed or refractory CLL or SLL who have previously received at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.

Data showed that liso-cel (n = 65) elicited a complete response (CR) rate of 20% (95% CI, 11.1%-31.8%), alongside a noteworthy achievement of minimal residual disease negativity, Kenderian reports. While acknowledging potential avenues for enhancement in CAR T-cell therapy for CLL/SLL, the ability of liso-cel to induce CR in 1 in 5 heavily pretreated patients lacking effective options underscores its significant clinical impact, Kenderian states. Notably, at the data cutoff date, patients who achieved the CR experienced a median duration of response that was not yet reached (NR; 95% CI, 15 months–NR).

Regarding safety, liso-cel exhibited low rates of toxicities, particularly cytokine release syndrome (CRS), attributed partly to its balanced CD4 and CD8 CAR T cell ratio, Kenderian states. Toxicity profiles observed in TRANSCEND CLL 004 align with prior trials of liso-cel; however, CRS and neurotoxicity rates were notably subdued, he reports. This trend is particularly promising for diseases prevalent in older, heavily pretreated populations, Kenderian expands. Most CRS events were of grade 1/2 severity, with 9% escalating to grade 3/4. Similarly, neurotoxicity predominantly manifested as grade 1/2 events. These findings collectively suggest a favorable safety profile for liso-cel, reinforcing its potential as a therapeutic option for patients with CLL whose disease is refractory to standard treatments, Kenderian concludes.

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Saad J. Kenderian, MB, CHB, consultant, discusses the safety and efficacy findings derived from the phase 1/2 TRANSCEND CLL 004 study in CLL/SLL.

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 chronic 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.

Saad J. Kenderian, MB, CHB, discusses ongoing research taking place to potentially move liso-cel into earlier lines of therapy for patients with CLL.

Dr Kenderian on the FDA Approval of Liso-Cel in Relapsed/Refractory CLL/SLL

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 the significance of the FDA approval of lisocabtagene maraleucel (liso-cel; Breyanzi) for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL).

the FDA granted accelerated approval to liso-cel

 for the treatment of adult patients with relapsed/refractory CLL or SLL who have been treated with 2 or more prior lines of therapy, including a BCL-2 inhibitor and a BTK inhibitor. This regulatory decision was supported by findings from the phase 1/2 TRANSCEND CLL 004 trial (NCT03331198), in which patients who received liso-cel achieved an objective response rate (ORR) of 45% (95% CI, 32.3%-57.5%), including a complete response (CR) rate of 20% (95% CI, 11.1%-31.8%). The median duration of response (DOR) in the entire population was 35.3 months (95% CI, 12.4-not yet reached [NR]), and the median DOR in the patients who achieved a CR was NR (95% CI, 15-NR). Moreover, the median time to first response was 1.1 months (range, 0.8-17.4), and the median time to first CR was 3.0 months (range, 1.1-17.9).

The ORR observed with liso-cel in patients with CLL/SLL is notable, Kenderian says, emphasizing that 20% of patients who receive this therapy experienced deep CRs and may be cured of their disease. Some of the first patients with CLL to receive CAR T-cell therapy remain in remission approximately 10 years after CAR T-cell infusion, Kenderian adds. Furthermore, some patients with CLL/SLL who received liso-cel in the TRANSCEND CLL 004 trial remain in remission 4 or more years after liso-cel infusion, Kenderian notes. Overall, the FDA approval of liso-cel in CLL/SLL allows more patients who progressed on other available therapies the opportunity to receive another effective option, Kenderian concludes.

Saad J. Kenderian, MD, CHB, discusses the FDA approval of lisocabtagene maraleucel for chronic lymphocytic leukemia or small lymphocytic lymphoma.

Saad J. Kenderian, MB, CHB

Articles

Dr Kenderian on the Efficacy of Liso-Cel in R/R CLL/SLL

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

Dr Kenderian on the FDA Approval of Liso-Cel in Relapsed/Refractory CLL/SLL