Safety and Efficacy of Chimeric Antigen Receptor T-Cell Therapy in Octogenarian Patients (Aged ≥ 80) with Relapsed or Refractory (R/R) Large B-Cell Lymphoma (LBCL)
Authors: Lee Dasom , Bharadwaj Sushma , Rana Masooma S , Jensen Alexandria , Wang William , Ghalehsari Nima , Sahaf Bita , Mallampet Jayasindhu , Elkordy Sarah , Latchford Theresa , Arai Sally , Johnston Laura , Hosoya Hitomi , Lowsky Robert , Negrin Robert S. , Rezvani Andrew R. , Shizuru Judith , Meyer Everett H. , Shiraz Parveen , Mikkilineni Lekha , Weng Wen-Kai , Maeda Lauren S. , Smith Melody , Sidana Surbhi , Muffly Lori , Frank Matthew J. , Miklos David B. , Dahiya Saurabh 
Published: December 2024

Background
Anti-CD19 chimeric antigen receptor T-cell therapy (CAR-T) is an effective therapy for patients (pts) with R/R LBCL. Recent real-world studies demonstrated safety and efficacy in elderly pts comparable to outcomes observed in pivotal registration trials (Tun AM, et al. Blood 2023). However, there is a dearth of data highlighting the experiences of octogenerian pts (aged ≥80) in the real-world setting. Here, we report a single-institution experience describing the safety and efficacy of CAR-T in octogenerian pts as well as correlative data in comparison to those of pts aged 65-79 (comparator cohort).
Method
In this retrospective analysis, pts aged ≥80 who underwent standard of care CAR-T for R/R LBCL at our institution between January 1, 2018 and June 30, 2024 were identified. Forty-two pts aged 65-79, out of 90, were selected based on 2:1 propensity matching algorithm that minimized the overall difference in propensity score between the octogenerian and comparator cohorts. Propensity matching was based on sex, ECOG, lactate dehydrogenase level, stage, and line of therapy for CAR-T. Comorbid conditions were assessed using the modified cumulative illness rating scale (CIRS) (Salvi F, et al. AGS 2008). Absolute CAR T-cell count was measured using flow cytometry at days 7, 14, 21, and 28 after infusion, and peak CAR expansion was collected as higher value at days 7 and/or 14 (Hamilton MP, et al. Blood Advances 2024). Continuous outcomes were compared using a multivariable linear regression, binary outcomes using multivariable logistic regression, and time-to-event outcomes using a Cox proportional hazards model. G-computation was used as a framework for estimating average treatment effects with cluster-robust standard errors to account for the matched memberships.
Results
We identified 21 pts in the octogenerian cohort (aged ≥80) and matched with 42 pts in the comparator cohort (aged 65-79). Pt-related characteristics were similar between the two cohorts including comorbidities assessed according to the CIRS criteria. All pts, except one pt receiving tisagenlecleucel in the octogenerian cohort, received either axicabtagene ciloleucel or lisocabtagene maraleucel (liso-cel). More pts in the octogenerian cohort received liso-cel (n=8 vs 1, 38% vs 2%; P&lt;0.01), bridging therapy (n=15 vs 23, 71% vs 55%; P=0.32), and bendamustine (n= 6 vs 3, 29% vs. 7%; P=0.06) as lymphodepleting agent.
Among the pts with evaluable data, the median follow-up time was 11.6 (IQR 2.8-18.0) months for the octogenerian cohort (n=18) and 24.7 (IQR 16.0-31.1) months for the comparator cohort (n=36). Overall response rate was similar between the octogenerian and comparator cohort (94% and 92%; P=0.23) as well as complete response rate (88% and 81%, P=0.69). 12-month progression free survival (PFS) was 47% (95% CI: 18-72%) for the octogenerian cohort and 56% (95% CI: 37-71%) for the comparator cohort (P=0.45). 12-month overall survival (OS) was 73% (95% CI: 42-89%) for the octogenerian cohort and 75% (95% CI: 55-87%) for the comparator cohort (P=0.19).
Any-grade CRS was 83% (grade [gr] ≥3, 11%) for the octogenerian cohort and 100% (gr ≥3, 0%) for the comparator cohort. Any-grade ICANS for the octogenerian and comparator cohort was 61% and 72%, respectively (P=0.74), while gr ≥3 ICANS was 33% and 25%, respectively (P=0.37). No death from CRS and ICANS was reported. ICU admission was required in 4 pts (22%) in the octogenerian cohort as compared to 1 pt (3%) in the comparator cohort. Median length of hospital stay was 21 (IQR, 15-26) days for the octogenerian cohort and 14 (IQR, 12-20) days for the comparator cohort (P&lt;0.05). One-year non-relapse mortality (NRM) was 11% (1 infection and 1 bowel perforation) in the octogenerian cohort and 3% (1 infection) in the comparator cohort.
The median of peak CAR T-cells was 3.46 (IQR 0.96-27.50) cells/ul for the octogenerian cohort (n=11) and 4.04 (IQR 1.69-19.97) cells/ul for the comparator cohort (n=35, P=0.94).
Conclusion
The octogenerian cohort (aged ≥80) demonstrated comparable efficacy, CAR related toxicity, and peak CAR expansion to that of the comparator cohort (aged 65-79). The octogenerian cohort experienced longer hospital stays and appeared to have higher rates of ICU admission rates. This analysis suggests that pts aged ≥80 should not be excluded from CAR T-cell therapy solely due to advanced age. Pt selection criteria and best supportive care practices need to be established.