Favorable survival for older adults treated with Axi-cel and Tisa-cel CD19 CAR-T therapy for relapsed/refractory DLBCL: a U.S. multicenter comparative analysis.

BACKGROUND

Diffuse large B-cell lymphoma (DLBCL) commonly affects older patients > 65 years old, with chimeric antigen receptor T-cell (CAR-T) therapy becoming an increasingly valuable treatment modality for relapsed/refractory (R/R) disease. Real world data on safety, efficacy, and management practices of CAR-T for older patients are important to inform clinical practice and referral.

OBJECTIVE

To compare efficacy and toxicities of axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) in younger (age <65) and older (age ≥ 65) patients with R/R DLBCL, and to describe clinical management practices for delivery of care to older patients.

STUDY

DESIGN

We conducted a retrospective, multicenter analysis of 351 adult patients with R/R DLBCL using data from the Cell Therapy Consortium registry. Patients who underwent apheresis for commercial axi-cel or tisa-cel products from early 2018 to late 2021 were compared by age: 194 patients < 65 years old and 157 patients ≥ 65 years old. Survival was estimated using the Kaplan-Meier method with 95% confidence intervals and compared using the log-rank test. Univariate and multivariate Cox proportional hazards regression was performed to identify factors associating with progression-free survival (PFS) and overall survival (OS).

RESULTS

328 patients (93.5%) were infused with CAR-T product. Combining all CAR-T products, younger and older groups yielded similar overall response rates (ORR, 61% vs 64%) and complete response rates (CR, 43% vs 49%). When evaluating only those who received axi-cel (n = 65), the older group had improved ORR (82% vs 65%, p = 0.02) and CR rates (63% vs 47%, p = 0.04) compared to younger patients. Median PFS (4.4 months in younger vs 6.8 months in older, p=0.44) and OS (22 months in younger vs 18 months in older, p=0.85) were similar between the two groups. In this cohort, 70% developed cytokine release syndrome (CRS, 6% grade > 3) with no significant difference by age overall or within same CAR-T product. In total, 71 patients (38%) developed immune effector cell-associated neurotoxicity syndrome (ICANS) with 23% being grade ≥ 3. There was no difference in any grade ICANS between younger and older patients. On multivariate analysis, overall mortality was increased in patients with high IPI (HR 1.71, p < 0.01) and bulky disease (HR 1.96, p < 0.01). Age group or CAR-T product were not associated with PFS or OS at 2 years. Rates of early infection, severe (grade >3) cytopenias at 3 months, and 100-day and 1-year non-relapse mortality (NRM) were also similar between younger and older patients.

CONCLUSION

Data from our Cell Therapy Consortium retrospective analysis demonstrate that CAR-T recipients older than 65 yrs experience favorable outcomes and manageable toxicity similar to younger patients. Our results support the practice that age alone should not be a barrier to CAR-T consultation or therapy.