TRANSFORM Trial: Clinical Perspectives in Liso-Cel CAR T-Cell Therapy for Second-Line R/R LBCL

Lisocabtagene maraleucel (liso-cel) was evaluated in a well-structured randomized clinical trial comparing it to standard-of-care chemotherapy followed by autologous stem cell transplant. A unique aspect of this study was the opportunity for crossover—patients whose chemotherapy failed were able to receive chimeric antigen receptor T-cell therapy. While this likely improved outcomes in the control arm, it may have also contributed to the trial’s inability to demonstrate a statistically significant overall survival benefit, unlike the ZUMA-7 trial. Additionally, the relatively small sample size of 184 patients may have limited the power needed to detect such a difference.

Despite this, the results were still clinically meaningful. With nearly 3 years of follow-up, a majority of patients—particularly those in the liso-cel arm—were alive, indicating the long-term durability of this treatment. Compared to axicabtagene ciloleucel (axi-cel), liso-cel tends to have a lower incidence of cytokine release syndrome and neurologic toxicity, making it an attractive option for patients who may be more frail or at higher risk for treatment-related complications. That said, one drawback early in the liso-cel trial was a higher rate of manufacturing failures or out-of-specification products, though this has become less of a concern in current clinical practice.

Clinicians often consider axi-cel for aggressive, rapidly progressing disease because of its shorter manufacturing time and proven survival advantage in earlier-line settings. In contrast, liso-cel is often selected for patients with more indolent disease or who may not tolerate the higher toxicity risk of axi-cel. Ultimately, both are valuable therapies, and their differing profiles allow oncologists to tailor treatment based on individual patient needs and disease characteristics, especially in the setting of relapsed or refractory large B-cell lymphoma.