In a significant development for older adults with relapsed/refractory large B-cell lymphoma (R/R LBCL), the use of CD19-focused chimeric antigen receptor (CAR) T-cell therapy demonstrates comparable survival outcomes to those seen in younger patients. This finding highlights the therapy's benefits in older populations, commonly diagnosed with this form of non-Hodgkin lymphoma.

"Our real-world study confirms the feasibility of CD19 CAR-T cell therapy for patients aged 75 and above," said Dr. Pierre Bories, MD, PhD, from the Institute for Cancer Strasbourg Europe in Alsace, France. He shared this research during the European Hematology Association (EHA) 2024 meeting in Madrid, Spain.

Patients with R/R LBCL often fall into older demographics, with many over 75 years old. However, these age groups have largely been underrepresented in prior clinical trials investigating CD19 CAR T-cell therapies, despite notable improvements seen in patients benefiting from these treatments.

To explore outcome differences between older and younger populations treated with CAR-T, Dr. Bories and his team conducted a retrospective assessment, analyzing 1524 patients from the French DESCAR-T registry. These individuals received treatment between April 2018 and September 2023, with care provided across 31 centers in France. All participants underwent at least two prior infusions of CAR-T cell therapy.

Among the study group, 1065 patients (representing 69.8%) were treated with axicabtagene ciloleucel (axi-cel), while the rest (30.1%, n=459) received tisagenlecleucel (tisa-cel).

The study revealed that 125 patients were aged 75 or older (median age: 76), while 1399 patients were younger than 75 (median age: 62). Key variations between the two groups included gender, LBCL subset, treatment history, performance status, and other prognostic factors such as age-adjusted International Prognostic Index (IPI).

Patients above 75 had higher hematopoietic cell transplantation–specific comorbidity index (HCT-CI) scores compared to their younger counterparts (31.2% vs. 16.8%, P < .001). Additionally, those over 75 had undergone fewer prior transplants (4.8% vs 21.8%, P < .001) and were more likely to receive tisa-cel (43.2% vs 28.9%, P < .001).

From the 1457 patients who had response data and median follow-up of 12.7 months, there were no marked disparities in overall response rate (ORR) or complete response rate (CRR) between age groups. Among patients aged 75 or older, 74.8% achieved ORR and 62.6% reached CRR, compared to 78.0% and 60.8%, respectively, in the younger subset (P = .425, P = .699).

Survival outcomes also remained similar between groups. The estimated median overall survival (OS) was 18.3 months for those aged 75 and above versus 24.0 months in the younger group (P = .12). Progression-free survival (PFS) estimates were also comparable, with 8.2 months for the older group and 6.1 months in younger patients (P = .73).

In terms of treatment safety, there were no significant variations in grade 3 or higher cases of cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS). CRS was seen in 7.3% of patients aged 75 or older versus 7.4% in younger individuals (P = .97). ICANS occurred in 9.8% and 12.4%, respectively (P = .39).

Admission rates to the intensive care unit (ICU) were similar between both groups, affecting roughly 24% of patients. Mechanical ventilation needs were also consistent, with around 3% of patients requiring it.

However, non-relapse mortality was notably higher in the 75+ age group, where 19.5% of deaths were unrelated to lymphoma progression or relapse, compared to just 8.1% in younger patients (P < .0001).

Breakdowns of early non-relapse mortality, defined as death within 28 days of infusion, revealed 2.4% of patients aged 75 and older experienced early mortality, representing 12.0% of non-relapse deaths, compared with 1.2% of younger patients (13.1% of non-relapse deaths).

Infections remained the predominant cause of non-relapse mortality in both groups, contributing to 57.7% and 54.2% of such deaths in those younger and older than 75, respectively. The likelihood of death from infection, CRS, or other causes was higher in older patients (P = .0003, P = .022, P = .0004), though ICANS rates did not differ significantly (P = .524).

"Our results illustrate heightened non-relapse mortality in older patients driven largely by late infections occurring more than 28 days post-treatment," Dr. Bories remarked. "Despite higher mortality from infections and CRS in older patients, this did not compromise overall survival in our study."

Addressing a question regarding the increased risk of infection in older patients, Dr. Bories emphasized the importance of close monitoring for frail individuals and suggested extended use of prophylactic measures.

Further research by Dr. Bories' team is underway, focusing on a propensity-matched comparison of axi-cel and tisa-cel in older patients.

The findings align with those from earlier studies, including a 2024 multicenter study of 172 diffuse LBCL (DLBCL) patients treated with CAR-T therapy, primarily axi-cel, which showed consistent PFS and OS results across both age groups. Of note, however, that study found no significant differences in non-relapse mortality between age groups.

The previous study also revealed no age-based disparities in ORR, with response rates exceeding 75%. However, a higher risk of relapse or death was associated with tisa-cel treatment, largely due to poor survival outcomes among patients younger than 70 years.

"Some evidence suggests that axi-cel may be more effective than tisa-cel in patients 65 and older, despite higher rates of neurotoxicity," the study authors noted.

Nonetheless, they concluded that "CAR T-cell therapy should not be withheld from elderly DLBCL patients with relapsed/refractory disease."

Low Utilization of CAR-T in the Elderly

Despite promising outcomes, the use of CAR-T cell therapy remains relatively low among older patients, as demonstrated in recent real-world investigations. A study of 551 older DLBCL patients found that 19% of those aged 65-69, 22% of those aged 70-74, and only 13% of those aged 75 and above, received CAR-T therapy.

"While older DLBCL patients show favorable event-free survival rates from CAR-T therapy comparable to younger patients, its usage remains low in this group," explained Dr. Dai Chihara, MD, PhD, of MD Anderson Cancer Center. He suggested an increased need for more accessible and tolerable CAR-T therapies for older adults.

Dr. Bories disclosed associations with several pharmaceutical companies, including Kite Gilead, Novartis, BMD-Celgene, Abbvie, Servier, and Janssen.

This article originally appeared on MDedge.com as part of the Medscape Professional Network.

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