Second-Line Axi-Cel and Liso-Cel Lead as Standards of Care in LBCL

As CAR T-cell therapies reshape the large B-cell lymphoma (LBCL) treatment paradigm, particularly with axicabtagene ciloleucel (axi-cel; Yescarta) and lisocabtagene maraleucel (liso-cel; Breyanzi) in the second-line setting, head-to-head studies comparing the 2 therapies could be helpful in terms of personalizing treatment for patients, according to Supriya Gupta, MD.

“We’re interested in seeing what the future of CAR T-cell therapy holds; however, as of now, both axi-cel liso-cel are great therapies in the second-line setting,” Gupta said during an interview with OncLive®. “[CAR T-cell therapy] has become the new standard of care [SOC] for patients [patients with LBCL] who’ve had early relapse or primary refractory disease to their initial frontline chemoimmunotherapy.”

Gupta is an assistant professor of Medicine, Hematology, Oncology and Transplantation at the University of Minnesota Medical School in Minneapolis.

In the interview, Gupta highlighted axi-cel–related data from the phase 3 ZUMA-7 trial (NCT03391466) and their potential implications in clinical practice, explained the use of axi-cel in the real-world setting, and discussed the phase 3 TRANSFORM trial (NCT03575351) evaluating liso-cel.

OncLive: What were the key data from ZUMA-7 and their potential implication?

Gupta: Axi-cel is widely used in the second-line setting. ZUMA-7 [included] over 350 patients [who were randomly assigned] 1:1 to receive either axi-cel or standard of care. The results favor axi-cel with a superior overall response rate [ORR] and complete response [CR] rate, as well as [a median] event-free survival [EFS], which [also] favors axi-cel. The toxicity profile [of axi-cel] was tolerable. [Any-grade cytokine release syndrome (CRS) was observed in] 92% of patients [n = 170], although the majority [of CRS events] were manageable, just grade 1/2, and 21% of patients had grade 3 or higher neurotoxicity episodes.1 [Overall,] the tolerability of axi-cel is good, and it has great long-term outcomes. I will say, there are no head-to-head trials in comparison to liso-cel; we don’t know which one is better than the other, but both are great therapies to consider in the second-line setting.

How do real-world data help inform clinical practice decisions in LBCL, specifically with axi-cel?

In a real-world study from the CIBMTR [Center for International Blood and Marrow Transplant Research], approximately 37% of the patients were [65 years of age and older], and many of the patients [had at least 1] clinically significant comorbidity. In the real-world setting, the ORRs and CRs were similar to those seen in the ZUMA-7 trial, as were the rates of CRS and immune effector cell-associated neurotoxicity syndrome. Therefore, the real-world data do seem to show that axi-cel is well tolerated, even in comorbid individuals, as well as elderly individuals.

Based on data from TRANSFORM, what is the role of liso-cel in second-line LBCL?

Similar to ZUMA-7, TRANSFORM evaluated 184 patients [who were randomly assigned] to either liso-cel or SOC, which is autologous stem cell transplant. This study also showed promising results, favoring liso-cel over SOC with a greater ORR [and]CR, as well as an improvement in EFS. [Liso-cel demonstrated a] tolerable safety profile, and the any-grade CRS rate was 49% [in this arm (n = 92)], with the majority of [events] being grade 1/2, and the neurotoxicity rate was significantly lower [vs SOC].2 We cannot do cross-trial comparisons, since the trial populations are quite different between liso-cel and axi-cel. [Findings from] the 3-year update from TRANSFORM that were recently published [in the Journal of Clinical Oncology] suggest that this particular therapy is significantly superior compared with SOC, with a [median] EFS of 29.5 months [95% CI, 9.5-not reached] compared with 2.4 months [95% CI, 2.2-4.9] with SOC.3

How have the FDA approvals of axi-cel and liso-cel affected the LBCL treatment paradigm?

With both axi-cel and liso-cel now available, there’s no CAR T-cell therapy that is considered superior to the other. There are no head-to-head trials that have been done, at least as of now. A lot of times the decisions regarding therapy are based on center preferences as well as case-specific factors. In general, the factors that influence clinical decisions [include] age, the functional status of the patient, frailty, and comorbidities. There’s a view that perhaps liso-cel may be safer to use, given that it has a more favorable toxicity profile and lower rates of CRS. However, that’s doing a cross-trial comparison, which is not ideal. In the future, I would love to see some prospective studies that assess axi-cel vs liso-cel, either as a pragmatic clinical trial or as a real-world [study], to suggest which one would be perhaps superior to the other.

References

1. Locke FL, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel as second-line therapy for large B-cell lymphoma. N Engl J Med. 2022;386(7):640-654. doi:10.1056/NEJMoa2116133
2. 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
3. Kamdar M, Solomon SR, Amason J, et al. Lisocabtagene maraleucel versus standard of care for second-line relapsed/refractory large B-cell lymphoma: 3-year follow-up from the randomized, phase III TRANSFORM study. J Clin Oncol. 2025;43(suppl 24):2671-2678.doi:10.1200/JCO-25-00399