Real-World Data Highlight Favorable Responses to Liso-Cel for R/R CLL

In a real-world setting, patients with relapsed or refractory CLL had favorable response rates to the CAR T-cell therapy lisocabtagene maraleucel.

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Patients with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL) experienced favorable response rates to the gene therapy lisocabtagene maraleucel (Breyanzi; liso-cel), even if they have been heavily pretreated, according to newly released real-world evidence. The findings offer some of the first insights into the chimeric antigen receptor (CAR) T-cell therapy’s performance outside of a clinical trial setting. The data were presented at the American Society of Hematology’s 2025 Meeting and Exposition, which was held December 6-9 in Orlando.1

Liso-cel was approved by the FDA in 2024 for the treatment of people with R/R CLL who have had at least 2 prior lines of therapy, including a Bruton tyrosine kinase (BTK) inhibitor and a BCL-2 inhibitor.2 In the phase 1/2 TRANSCEND-CLL 004 trial, the complete response (CR) or remission rate was 18% (95% CI 9-32; P = .0006).3 That rate included participants with incomplete marrow recovery. The overall response rate (ORR) was 43% (95% CI, 29-58). The trial’s investigator-assessed CR and ORR rates—which were based on the International Workshop on CLL (iwCLL) 2018 criteria—were somewhat higher, at 24% and 57%, respectively.

However, that trial had strict inclusion and exclusion criteria, explained the authors of the new real-world study, which included first author Jennifer Huang, MD, PhD, of the Fred Hutch Cancer Center.

The new study of real-world treatment with liso-cel included 30 patients with ages ranging from 44 to 80 years and a median age of 67 years. They were treated at multiple institutions in the United States and received commercial liso-cel. Patients with Richter transformation were excluded from the trial.

Most of the patients (67%) had either del17p or mutated TP53; 8 patients had complex karyotype cancers, which were defined as at least 3 abnormalities. Patients had received a range of 1 to 12 previous lines of therapy, with a median of 6 prior lines, and 80% had been treated with chemotherapy. Per FDA guidelines, all patients had been previously treated with a covalent BTK inhibitor and a BCL-2 inhibitor. All but one patient had received bridging treatment that was stopped after leukapheresis, the authors said.

Twenty-seven participants (90%) had been treated with the non-covalent BTK inhibitor pirtobrutinib (Jaypirca), including 18 for whom pirtobrutinib was the last line of therapy before liso-cel. Twelve of those patients stopped taking pirtobrutinib between leukapheresis and lymphodepletion, Huang and colleagues said. The other 6 patients resumed pirtobrutinib following liso-cel.

At the time they received liso-cel, 1 patient was in CR and 25 patients had a partial response.

Patients were assessed using iwCLL criteria. Participants who did not undergo a bone marrow biopsy but who otherwise met the criteria for CR were categorized as having an unconfirmed CR (CRu).

The best CR/CRu rate among the cohort was 60%, which included 1 patient with CRu. The best ORR was 83.3%. The median time to best response was 30 days.

The results varied significantly based on whether pirtobrutinib had been the patient’s last line of therapy before liso-cel. Those who received pirtobrutinib as their last line of therapy before liso-cel had a CR/CRu rate of 72%, compared to 28% for those whose final line of therapy before liso-cel was not pirtobrutinib. Among 14 patients who underwent measurable residual disease (MRD) assessment via flow cytometry, the undetectable MRD (uMRD) rate was 64%; among 17 patients who underwent next-generation sequencing-based MRD assessment, the uMRD rate was 41%.

Safety data showed that 3 patients experienced grade 3 cytokine release syndrome (CRS), though 26 patients experienced any-grade CRS. Twelve patients experienced immune effector cell–associated neurotoxicity syndrome (ICANS), including 4 with grade 3 syndrome. No patients experienced grade 4 or 5 CRS or ICANS.

Most patients (n = 27) were still alive at the time of data collection, the authors noted.

The study's median follow-up was just 3.3 months, constituting a limitation of the study. The sample size was also small, and the study was retrospective in nature, they noted. Still, the authors wrote that their findings offer encouraging data, particularly with regard to the use of pirtobrutinib prior to liso-cel.

References

1. Huang J, Voutsinas J, Khaire N, et al. Superior real-world outcomes of lisocabtagene maraleucel in chronic lymphocytic leukemia. Presented at: ASH 2025; December 6-9, 2025; Orlando, Florida. Abstract 798.

2. Caffrey M. FDA grants accelerated approval to liso-cel for CLL/SLL after BTK, BCL-2 inhibitors. AJMC®. March 15, 2024. Accessed December 23, 2025. https://www.ajmc.com/view/fda-grants-accelerated-approval-to-liso-cel-for-cll-sll-after-btk-bcl-2-inhibitors

3. Siddiqui 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