Real-World Analysis Reveals Favorable Outcomes With Liso-Cel in CLL

OncLive^® first published this article.

An analysis presented during the 2026 Transplantation and Cellular Therapy Meetings shed light on the positive real-world outcomes of patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who were treated with lisocabtagene maraleucel (liso-cel; Breyanzi; Bristol Myers Squibb).¹

The overall response rate (ORR) reported in evaluable patients (N = 41) was 85% (n = 35), which included a complete response (CR) rate of 44% (n = 18), an unconfirmed CR rate of 5% (n = 2), and a CR with incomplete blood count recovery rate of 7% (n = 3). The median time to best response was 30 days. At a median follow-up of 3.3 months, the 6-month progression-free survival rate was 92% (95% CI, 83%-100%); 1 patient relapsed. The 6-month overall survival rate in those with a CR was 88% (95% CI, 74%-100%) vs 100% (95% CI, 100%-100%) in those without a CR. Three of the 41 patients died.

Given the results of the TRANSCEND CLL 004 trial (NCT03331198), investigators wanted to evaluate the relationship between pirtobrutinib (Jaypirca; Eli Lilly) as the last line of therapy and achievement of CR. Sixty-five percent of those who received pirtobrutinib as their last line of therapy (n = 24) experienced a CR vs 35% of those who received another treatment strategy (n = 17; P = .3). The P value between pirtobrutinib exposure and response rate was not statistically significant.

Some patients were also treated with Bruton tyrosine kinase (BTK) inhibitors besides pirtobrutinib. As such, investigators evaluated the association between any exposure to BTK inhibition and efficacy. Of those who received any BTK inhibitor as their last line of therapy (n = 31), 83% achieved a CR vs 17% of those who did not (n = 10); this association was not statistically significant (P = .4).

“The real-world CR [rate] and ORR of liso-cel for patients with relapsed or refractory CLL is 56% and 85%, respectively,” Jennifer Huang, MD, PhD, said in a presentation of the data. “This response rate is better than that of liso-cel monotherapy as described in TRANSCEND, and efficacy is perhaps more consistent with the TRANSCEND ibrutinib [Imbruvica] cohort. This may be due to the high utilization of BTK inhibitors, including pirtobrutinib as bridging therapy.”

Huang is a physician and assistant professor in the Clinical Research Division at Fred Hutch Cancer Center in Seattle, Washington, as well as an assistant professor in the Division of Hematology and Oncology at the University of Washington School of Medicine.

Real-World Examination of Liso-Cel in CLL

In March 2024, the FDA granted accelerated approval to liso-cel for use in adult patients with relapsed or refractory CLL/SLL who had received at least 2 previous lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.² The decision was supported by earlier findings from TRANSCEND CLL 004, in which treatment with the chimeric antigen receptor (CAR) T-cell therapy (n = 65) led to a 20% (95% CI, 10.0%-33.7%) CR rate; the ORR was 44% (95% CI, 30.0%-58.7%).³ Huang added that concurrent administration of liso-cel and ibrutinib (Imbruvica; Pharmacyclics/Johnson & Johnson) also led to a CR rate of 45% (95% CI, 31%-60%); the ORR was 86% (95% CI, 74%-95%).⁴

The real-world safety and efficacy of the CAR T-cell therapy in this population are largely unknown, she added.¹ To this end, the multi-institutional, retrospective CARE CAR-T CLL study (Collaborative Assessment of Real-World Evidence of Lisocabtagene Maraleucel in Patients with Relapsed/Refractory CLL/SLL) was launched.

The study included patients who were given commercial liso-cel for CLL/SLL in the US at 19 clinical sites; those with Richter transformation were excluded from analysis. Responses were evaluated leveraging International Workshop on Chronic Lymphocytic Leukemia criteria, and the American Society for Transplantation and Cellular Therapy criteria were used to grade cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS).

In the total of 41 patients, the median age was 68 years (range, 62-72). Most patients were male (71%), White (85%), and not Hispanic or Latino (95%). The median Cumulative Illness Rating Scale score was 4 (Q1, Q3: 2, 7). Patients could have had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (27%), 1 (59%), 2 (10%), and 3 (5%).

Moreover, 9% of patients had an intermediate CLL International Prognostic Index (IPI) score, whereas 41% had a high score and 50% had a very high score; this score was unknown for 9% of patients. Most patients had bulky disease that was smaller than 5 cm (80%). Moreover, the majority of patients had high-risk cytogenetics in the form of del17p or TP53 mutations (63%); a little more than one-third of patients (39%) had complex karyotypes.

In terms of treatment history, 76% of patients received prior chemotherapy, with a median of 1 line of chemotherapy received. The median number of any prior lines of treatment was 6 (Q1, Q3: 4, 7). Most patients (95%) received 3 or more prior lines of any treatment; 73% of patients had received 5 or more prior lines of any treatment. Treatment history included BTK inhibition for all patients, BCL-2 inhibition for 95% of patients, and pirtobrutinib for 90%.

The majority (98%) of patients received bridging therapy, with stop times before leukapheresis (2%), between leukapheresis and lymphodepletion (68%), or continued post liso-cel (29%). Last lines of therapy before receipt of CAR T-cell therapy included the following:

• Covalent BTK inhibitor (5%)
• Noncovalent BTK inhibitor (51%)
• BCL-2 inhibitor (2%)
• Anti-CD20 monoclonal antibody (2%)
• BTK inhibitor and BCL-2 inhibitor (2%)
• BCL-2 inhibitor and anti-CD20 monoclonal antibody (5%)
• BTK inhibitor, BCL-2 inhibitor, and anti-CD20 monoclonal antibody (2%)
• Chemotherapy (10%)
• Other nonchemotherapy (20%)

Lastly, of those who received BTK inhibition as their last line of therapy, 59% received pirtobrutinib; 76% received any BTK inhibitor.

Subgroup Analyses and Safety Profile

Responses were observed with regard to patient and disease characteristics. Odds ratios for age, ECOG performance status (2 to 3 vs 0 to 1), CLL IPI score (very high vs high/intermediate), del17 or TP53 mutated (yes vs no), complex karyotype (yes vs no), and bulky disease (≥ 5 cm vs < 5 cm) were –0.46 (95% CI, –1.76 to 0.63), 0.31 (95% CI, –1.47 to 2.39), 0.79 (95% CI, –0.63 to 2.29), 0.69 (95% CI, –0.65 to 2.07), 0.61 (95% CI, –0.72 to 2.01), and –1.33 (95% CI, –3.44 to 0.49), respectively.

Responses were also assessed with regard to treatment history. The ORs for those with prior chemotherapy (yes vs no), more prior lines of treatment (≥ 5 vs < 5), fewer lines of treatment (≥2 vs 0-1), last line of treatment (BTK inhibitor vs no BTK inhibitor or pirtobrutinib vs other), and timing of discontinuation of last treatment (continued after lymphodepletion vs stopped between leukapheresis and lymphodepletion) were 0.03 (95% CI, –1.51 to 1.50), –0.76 (95% CI, –2.43 to 0.71), –0.13 (95% CI, –1.45 to 1.19), 0.86 (95% CI, –0.66 to 2.45), 0.76 (95% CI, –0.56 to 2.13), and 1.69 (95% CI, 0.13-3.69), respectively.

“CR correlates with less bulky disease and use of bridging therapy that extends past liso-cel infusion,” Huang said.

She added that the safety profiles was as expected.

In terms of CRS, 46% of patients experienced a grade 1 event (n = 19), 29% had a grade 2 event (n = 12), and 10% had a grade 3 event (n = 4). With regard to ICANS, 7% of patients had a grade 1 event (n = 3), 12% had a grade 2 event (n = 5), and 12% had a grade 3 event (n = 5). No grade 4 or 5 CRS or ICANS events occurred.

Huang noted that 3 patients experienced immune effector cell–associated HLH-like syndrome; 1 of these cases were grade 2, and 1 case was grade 5.

References

1. Huang J, Voutsinas J, Khaire N, et al. Favorable real-world outcomes of lisocabtagene maraleucel in chronic lymphocytic leukemia. Presented at: 2026 Transplantation and Cellular Therapy Meetings; February 4-7, 2026; Salt Lake City, UT. Presentation ID 60.
2. Breyanzi. Prescribing information. Bristol Myers Squibb; 2024. Accessed February 23, 2026. https://packageinserts.bms.com/pi/pi_breyanzi.pdf
3. Siddiqi T, Maloney DG, Kenderian SS, et al. Lisocabtagene maraleucel (liso-cel) in R/R CLL/SLL: 24-month median follow-up of TRANSCEND CLL 004. Blood. 2023;142(suppl 1):330. doi:10.1182/blood-2023-179529
4. Siddiqi T, Gauthier J, Kenderian SS, et al. Lisocabtagene maraleucel (liso-cel) in patients (pts) with relapsed or refractory (R/R) chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): Updated follow-up of Transcend CLL 004. Blood. 2024;144(suppl 1):4633. doi:10.1182/blood-2024-200840