The addition of lisocabtagene maraleucel (liso-cel Breyanzi) to the large B-cell lymphoma (LBCL) treatment paradigm has redefined the management of this disease, supported by data that show strong survival benefits over historical standards of care (SOCs), as well as a relatively favorable toxicity profile, according to Taylor Brooks, MD.
In an interview with OncLive®, Brooks discussed highlights from the phase 1 TRANSCEND NHL 001 trial (NCT02631044) dataset that supported the FDA approval of liso-cel in the third-line and later LBCL setting, findings from the phase 3 TRANSFORM trial (NCT03575351) that showed the superior efficacy of second-line liso-cel over standard chemotherapy and transplant in LBCL, and details of liso-cel’s toxicity profile that make it a treatment to consider for many patients with this disease.
He expanded on the role of axicabtagene ciloleucel (axi-cel; Yescarta) for LBCL management in another portion of the interview.
Brooks is an associate staff physician in the Department of Hematology and Oncology at the Cleveland Clinic Taussig Cancer Institute in Ohio; as well as a member of the Population and Cancer Prevention Program at Case Comprehensive Cancer Center.
OncLive: What were the key findings from the TRANSCEND NHL 001 trial of liso-cel in relapsed/refractory LBCL?
Brooks: After the efficacy of axi-cel was demonstrated, liso-cel in the TRANSCEND NHL 001 trial was evaluated in [270] patients, most of whom had relapsed/refractory, diffuse LBCL.1 The overall response rate was [73%] with [53%] of patients having a complete response [CR], and the median overall survival [OS] in that study was [27.3 months]. Most patients historically treated in this setting had much inferior outcomes.
What data led to the FDA approval of liso-cel in the second-line LBCL setting?
The effectiveness of liso-cel was also investigated in the TRANSFORM trial in a similar setting where patients with refractory or early relapsed LBCL received either liso-cel or 3 cycles of salvage chemotherapy followed by transplant in a prospective, randomized, head-to-head fashion.2 In this study, 74% of patients receiving liso-cel had a CR vs 43% of those in the SOC arm. At a median follow-up of [17.5] months, the median event-free survival favored liso-cel overall compared with chemotherapy and transplant. [The median] OS was not reached [NR] in liso-cel–receiving patients vs [29.9] months in patients who received the SOC. Similar to ZUMA-7, a prespecified subgroup analysis that adjusted for crossover from the transplant to liso-cel [arms] continued to find improved OS in patients who were intended to receive cellular therapy as an initial treatment strategy.
The effectiveness of liso-cel in this setting was also investigated in the single-arm phase 2 PILOT study [NCT03483103]. This study specifically enrolled patients who were deemed ineligible for transplant. Even among refractory and early relapsed patients, [54%] in this study had a CR, with a median progression-free survival of [9.0] months and a median OS that was NR.3 With the data demonstrated by TRANSFORM and PILOT, the use of [second-line] liso-cel for patients with refractory or early relapsed LBCL was approved by the FDA in June 2022.
What are the potential benefits of using liso-cel in relapsed/refractory LBCL as opposed to axi-cel, which is also FDA approved in this setting?
Being able to use liso-cel in the second-line setting for high-risk and early relapsing patients is changing the treatment paradigm. One of the most important and interesting questions to ask is: What is the comparative efficacy of the different cellular products that are available in this setting? It is hard to know without a direct head-to-head comparison, though some insights might be gleaned—but should be gleaned with caution—by comparing currently available clinical trial data.
One potential benefit of the use of liso-cel that seems to be shown again and again, either in study populations or real-world settings, is that the use of this construct seems to be associated with lower rates of important toxicities: cytokine release syndrome, immune effector cell–associated neurotoxicity syndrome, and perhaps even others like immune effector cell–associated hemophagocytic syndrome and immune effector cell–associated hematologic toxicities. Why is this the case? It’s not entirely clear. Some speculate that it is because of the [liso-cel] CAR T construct being different compared with axi-cel. Liso-cel has a 4-1BB construct, and axi-cel has a CD28 construct. Whatever the case, [liso-cel] seems to be able to be applied to a wider swath of patients with comorbidities without compromising outcomes.
References
- Abramson JS, Palomba ML, Gordon LI, et al. Two-year follow-up of lisocabtagene maraleucel in relapsed or refractory large B-cell lymphoma in TRANSCEND NHL 001. Blood. 2024;143(5):404-416. doi:10.1182/blood.2023020854
- Abramson JS, Solomon SR, Arnason J, et al. Lisocabtagene maraleucel as second-line therapy for large B-cell lymphoma: primary analysis of the phase 3 TRANSFORM study. Blood. 2023;141(14):1675-1684. doi:10.1182/blood.2022018730
- Sehgal A, Hoda D, Riedell PA, et al. Lisocabtagene maraleucel for R/R LBCL in patients not intended for HSCT: final results of the phase 2 PILOT study. Blood Adv. 2025;9(15):3694-3705. doi:10.1182/bloodadvances.2024015262
