Background: Chimeric antigen receptor T-cell (CAR-T) therapies represent a major advance in the management of relapsed/refractory multiple myeloma (RRMM), demonstrating durable responses in heavily pretreated patients in real-world and clinical trial settings. However, elderly patients are underrepresented in pivotal studies, leaving gaps in knowledge regarding their outcomes, toxicities, and infection risks compared to younger populations. Real-world data are essential for optimizing patient selection and management strategies in this vulnerable population.

Methods: We conducted a retrospective cohort analysis using the TriNetX Global Network to compare outcomes in RRMM patients aged ≥70 years and those aged 18–69 years who received FDA-approved CAR-T therapies. Two cohorts were identified: Cohort 1 (≥70 years, n=466) and Cohort 2 (18–69 years, n=466). Propensity score matching (1:1) was performed based on demographics, comorbidities, prior autologous stem cell transplant, and prior use of lenalidomide, cyclophosphamide, daratumumab, bortezomib, thalidomide, pomalidomide, and carfilzomib. The index event was the first administration of CAR-T therapy, and all outcomes were assessed in a 1-year window starting one day after the index date. Patients with a history of the outcome prior to the index event were excluded from that specific outcome analysis. Time-to-event outcomes were analyzed using Kaplan-Meier survival curves, with hazard ratios (HR) and log-rank p-values reported.

Results: Neurotoxicity events were numerically higher in the elderly (HR 1.23, 95% CI 0.75–2.02, p=0.41), but not statistically significant. Rates of neutropenia (HR 1.03, 95% CI 0.73–1.46, p=0.87), thrombocytopenia (HR 1.12, 95% CI 0.78–1.61, p=0.54), and anemia (HR 0.94, 95% CI 0.58–1.51, p=0.79) were also similar between cohorts.

Septic shock occurred with similar frequency (HR 1.44, 95% CI 0.59–3.52, p=0.42). Risk of pneumonia trended lower in the elderly but did not reach significance (HR 0.65, 95% CI 0.37–1.12, p=0.12). CMV infection rates were similar (HR 1.09, 95% CI 0.60–1.96, p=0.79), as were aspergillosis (HR 0.95, 95% CI 0.19–4.72, p=0.95), hypogammaglobulinemia (HR 0.89, 95% CI 0.69–1.16, p=0.39), and IVIG requirement (HR 0.90, 95% CI 0.73–1.12, p=0.34).

Incidence of MDS (HR 0.72, 95% CI 0.30–1.71, p=0.45) and AML (HR 0.53, 95% CI 0.24–1.14, p=0.10) was low in both groups and not significantly different.

Fatigue was comparable (HR 0.85, 95% CI 0.54–1.34, p=0.49). Rates of ESRD/HD were low and did not differ by age (HR 1.18, 95% CI 0.32–4.39, p=0.81).

Incidence of elevated interleukin-6 (≥40 pg/mL) was slightly lower in the elderly but not statistically significant (HR 0.74, 95% CI 0.42–1.30, p=0.29). Similarly, rates of elevated CRP (≥10 mg/L) (HR 1.03, 95% CI 0.79–1.33, p=0.85), hypogammaglobulinemia (IgG <500 mg/dL; HR 0.72, 95% CI 0.16–3.21, p=0.66), and elevated LDH (>250 U/L; HR 1.10, 95% CI 0.79–1.54, p=0.56) did not significantly differ between age groups. The risks of cytokine release syndrome (HR 0.9, 95% CI 0.70–1.20; log-rank p=0.51) and immune effector cell-associated neurotoxicity syndrome (HR 0.84, 95% CI 0.55–1.28; log-rank p=0.42) were similar between older and younger patients.

All-cause mortality did not differ significantly between cohorts (HR 0.87, 95% CI 0.59–1.26, p=0.45). Hospitalization risk was comparable (HR 0.94, 95% CI 0.57–1.56, p=0.86), as was the risk of ER visits (HR 1.00, 95% CI 0.61–1.65, p=0.99).Conclusions: In this large, real-world, propensity-matched analysis of CAR-T therapy for RRMM, elderly patients (≥70 years) experienced similar rates of mortality, healthcare utilization, inflammatory and hematologic toxicities, infectious complications, and secondary hematologic malignancies compared to younger counterparts. These findings support the use of CAR-T therapies in appropriately selected older adults, though continued vigilance for toxicity remains essential.

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2025
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