According to Irtiza N. Sheikh, DO, similar efficacy was seen among patients younger than 50 with large B-cell lymphoma (LBCL) who received lisocabtagene maraleucel (Breyanzi; liso-cel) in the real world vs clinical trial setting.
In a conversation with CancerNetwork®, Sheikh discussed a poster presentation he gave at the 2026 Tandem Meetings, which sought to compare the relative efficacy of liso-cel between patients younger than 50 and those 50 years and older in both the real-world and clinical trial settings. He began by outlining the background for conducting this research, which began as a desire to assess the impact of the adolescent and young adult (AYA) population, generally defined as patients between the ages of 18 and 25, who may be treated in the pediatric or adult oncology settings. Ultimately, his team expanded this younger cohort to include all patients younger than 50.
Regarding efficacy in the study, he highlighted statistical similarities across both group types based on age-related and trial-related differences, noting a trend toward more durable responses in the younger population. Next, he highlighted some key adverse effects (AEs) that emerged within the analysis, already having accounted for cytokine release syndrome (CRS) and immune effector cell-related neurotoxicity syndrome (ICANS) in the poster, but also touching upon some others that could be relevant in more granular safety analyses.
He concluded by outlining key questions to consider when assessing disparities across treatment settings, emphasizing that the answers may shed light on some discrepancies in outcomes. Finally, he expressed a hope that clinicians become comfortable administering liso-cel in earlier lines of therapy and emphasized its safety and tolerability in the younger LBCL population.
Sheikh is an assistant professor in the Department of Pediatrics – Patient Care, Stem Cell Transplantation and Cellular Therapy Section of the Division of Pediatrics at The University of Texas MD Anderson Cancer Center.
CancerNetwork: What was the background for conducting the study assessing liso-cel among younger patients with relapsed/refractory LBCL in the real-world and clinical trial settings?
Sheikh: When we first started brainstorming this project, our initial goal was to compare the outcomes between patients who are younger and received liso-cel vs those who are over the age of 50 and received liso-cel. The idea came out of an interest in a niche of oncology and transplantation medicine of AYA [patients]. The reason is the AYA population—or even those who are a bit older but not truly a geriatric age—don’t fit neatly into a box, especially those who are between the ages of 18 and 25.
Should these patients be treated on a pediatric clinical trial or an adult clinical trial? Should they be in pediatric hospitals or adult hospitals? Do they respond differently to therapies, and do they experience AEs at different rates compared with older patients, not just within the general population, but in the real-world and the clinical trial settings? When you’re looking at these AYA patients, you can then expand these points to patients not only on the younger age of the spectrum, but also in those who are less than 50, and then compare that with older patients.
Keeping that in mind, we also wanted to know if there’s a discrepancy between patient characteristics for those who are enrolled in a clinical trial who received liso-cel vs those in the real-world setting. This was a good opportunity to see if there are age-related differences [and] trial-related differences vs those who may be receiving liso-cel as a standard-of-care [regimen] or as part of a clinical trial at respective institutions.
What were some key differences in efficacy between patients treated in the real world vs the clinical trial setting?
It was interesting; we didn’t really see a statistically significant difference between the 2 groups. Both demonstrated that 12-month PFS rates were over 50%. However, when you look at the 12-month and 18-month duration of response, while the results weren’t statistically significant, there was a trend for a higher proportion of patients less than 50 who had a durable or a lasting response. I would say the take-home point is that in the younger patients with relapsed/refractory LBCL who are less than 50 years old and receive liso-cel, real-world and clinical trial settings both demonstrate that responses were deep and durable after treatment, which is similar to outcomes in overall populations.
Aside from ICANS/CRS, what other toxicities emerged? What strategies were employed to mitigate or manage them?
ICANS and CRS were the main toxicities that we were interested in. We also looked at other rates of other toxicities, like severe infections, prolonged cytopenias, and secondary lymphomas. What we saw was that both were similar between younger patients and the overall population, as well as in the real-world and the clinical trial settings. Our next step is going to be to look in more detail if there’s a difference in patient groups and other AEs like hemophagocytic lymphohistiocytosis [HLH], need for ICU admission, and any organ toxicity or dysfunction to further determine if there are differences in the toxicity profile between the younger and older patients.
To answer your question in terms of how to mitigate those AEs, it’s usually by using standard of care, whether it’s immunosuppressants or immune modulators like anakinra [Kineret], tocilizumab [Actemra], or antimicrobials. Those are all things that we’re going to [investigate] on a more granular level to see if there’s any difference between both clinical trial and real-world patients younger than 50, as well as the overall population.
How can the discrepancies between outcomes in the real-world and clinical trial settings be mitigated or rectified, and how can providers make care more equitable for these patients?
It’d be interesting to see if there are differences in clinical characteristics between institutions that are using liso-cel strictly on a clinical trial basis vs those who are giving it as standard of care. That may help answer where these inequities are coming from. We know that those in the real-world setting received at least 1 more line of prior systemic therapy compared with the clinical trial patients; it was a 3 vs 2 respective difference.
It was interesting to see; why did that [difference] exist? Why aren’t patients in the real-world setting going to liso-cel sooner? Of those who received liso-cel in the outpatient setting, how many had chemotherapy-refractory disease? Of those in the clinical trial setting, how many had more than 1 comorbidity, considering [at least half] in the real-world setting… did have more than 1 comorbidity? We don’t have those data for those who were enrolled on a clinical trial.
Overall, my hope is that we can make the cell therapy more accessible to centers that may not be classically associated with clinical trials and clinicians in other settings, including those who are focused on the outpatient setting. We want to communicate to them that they can feel comfortable giving liso-cel sooner [rather] than later in patients and not delay therapy, which is the whole crux of our project. That includes patients who may have been heavily pretreated [or] have multiple comorbidities because it does seem at least safe and effective in those populations.
Is there anything else that you would like to highlight that we might not have covered?
There’s a lot of improvements in outcomes, and there’s an advent of new, exciting drugs like liso-cel. This is a great time to [investigate] age-related differences to help us guide and personalize therapies for our patients based on not only disease but factors such as age, comorbidities, and any predictive factors like possible AEs. When it comes to liso-cel itself, it does appear that it’s safe and effective in patients less than 50 years old. I hope that clinicians are comfortable using it earlier in patients who have relapsed/refractory LBCL.
Reference
Sheikh IN, Patel K, Perales MA, et al. Clinical outcomes of lisocabtagene maraleucel (liso-cel) in YOUNGER PATIENTS (Pts) with relapsed or refractory (R/R) large B-cell lymphoma (LBCL). Presented at: 2026 Transplantation & Cellular Therapy Meetings of ASTCT and CIBMTR; February 4-7, 2026; Salt Lake City, UT. Abstract 210.