Real-World Evidence Shows CAR T-Cell Therapy Effective in Older Patients With Relapsed/Refractory DLBCL

Chimeric antigen receptor (CAR) T-cell therapy is effective in many older patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), but its use and efficacy appears to be lower in patients over the age of 75, according to new real-world data.

Study authors noted that the first CAR T-cell therapy for patients with relapsed or refractory DLBCL was approved in 2017.

“Development of CD19-directed autologous CAR T-cell therapy has resulted in a paradigm shift in the treatment of relapsed/refractory DLBCL, providing an effective treatment option for older patients who are not necessarily candidates for auto [stem cell transplant],” they wrote in Blood.

Still, the authors said no study has yet looked at real-world utilization of the therapy in older patients. To fill that research gap, they used a CMS database to identify patients aged 65 and older with diagnosed DLBCL to better understand the utilization and outcomes of CAR T-cell therapy in that age cohort.

The database includes records for all patients treated under Medicare fee-for-service plans. The authors found more than 70,000 patients aged 65 and older whose DLBCL was diagnosed between April 2016 and December 2020. Of those, 551 patients underwent CAR T-cell therapy and met the study’s inclusion criteria.

To gauge how often the therapy was used among people with 2 or more previous lines of therapy, the authors analyzed a subset of patients who had at least 2 years of continuous enrollment in Medicaid before their DLBCL diagnosis and for whom line of therapy was delineated in the data. Among those patients, 19% of people aged 65 to 69 years received CAR T-cell therapy in line 3 or beyond compared with 22% of patients aged 70 to 74 years and 13% of patients 75 years and older.

Eighty-three percent of patients who received CAR T-cell therapy received it in an inpatient setting, the authors said, and they stayed in the hospital for an average 21 days. The median total health care cost during the 90-day follow-up period was $352,572, the authors said.

The therapy had favorable efficacy rates, the investigators found. Overall, the median event-free survival (EFS) was 7.2 months, although success rates varied by age group. The investigators estimated 12-month EFS rates of 43% in the 65-to-69 age group, 52% in the 70-to-74 age group, and just 34% in the 75-and-older cohort.

The median overall survival was 17.1 months, which did not differ significantly between age groups, the authors found.

They said this real-world evidence shows that CAR T-cell therapy led to real-world outcomes that were like the outcomes reported in clinical trials.

“However, CAR T-cell therapy was not utilized in more than 80% of patients who received third-line treatment and beyond, highlighting significant barriers to this treatment among older patients,” the authors said.

The reasons for those low utilization rates are not known, although the investigators said the patients’ condition, disease progression, or lack of access to the therapy are possible reasons.

However, they also said that these data show that CAR T cells are not a panacea, particularly when it comes to the oldest patients.

“This study indicated an unmet need for more accessible, effective, and tolerable therapy in older patients, especially in patients aged ≥75,” they concluded.

Reference

Chihara D, Liao L, Tkacz J, et al. Real-world evidence of CAR T-cell therapy in older patients with relapsed/refractory diffuse large B-cell lymphoma. Blood. Published online June 20, 2023. doi:10.1182/blood.2023020197