Unveiling the Real-World Balance of Efficacy and Toxicity: CAR-T versus Bispecific Antibodies for Elderly Patients with Multiple Myeloma

Materials and Methods/Case Presentation/Objective: We performed a retrospective cohort analysis using the TriNetX Network. Patients aged ≥70 years with RRMM treated with either CAR-T (n=320) or bispecific antibodies (n=320) were identified. Cohorts were propensity-matched for demographics, comorbidities, stem cell transplant status, and prior therapies. Outcomes were assessed over 12 months from index therapy. Time-to-event outcomes were analyzed with Kaplan-Meier methods, with hazard ratios (HR) and log-rank p-values reported.

Results/Description/Main Outcome Measures: CAR-T was associated with lower all-cause mortality compared to bispecific antibodies (HR 0.45, 95% CI: 0.30–0.67, p< 0.001). Hospitalization risk was higher with CAR-T (HR 3.42, 95% CI: 1.41–8.32, p=0.004), ER visit rates did not differ significantly (HR 0.90, 95% CI: 0.48–1.67, p=0.738).

CAR-T had substantially higher incidence of cytokine release syndrome (HR 2.31, 95% CI: 1.56–3.42, p< 0.001), while rates of interleukin-6 elevation (≥40 pg/mL) were higher with CAR-T but did not reach statistical significance (HR 2.12, 95% CI: 0.92–4.92, p=0.072). Rates of CRP ≥10 mg/L (HR 1.62, 95% CI: 1.17–2.23, p=0.003) and LDH >250 U/L (HR 2.73, 95% CI: 1.70–4.40, p< 0.001) were both significantly more common in the CAR-T cohort.

Rates of ICANS (immune effector cell-associated neurotoxicity syndrome) were significantly higher with CAR-T (HR 1.82, 95% CI: 1.04–3.17, p=0.032). Hematologic toxicities were more prominent in the CAR-T group, including thrombocytopenia (HR 1.48, 95% CI: 0.90–2.43, p=0.117), anemia (HR 1.41, 95% CI: 0.69–2.89, p=0.343), and neutropenia (HR 2.77, 95% CI: 1.70–4.50, p< 0.001), though not all reached statistical significance.

Hypogammaglobulinemia was more frequent post-CAR-T (HR 1.78, 95% CI: 1.21–2.61, p=0.003). Use of IVIG was higher but not statistically significant in the CAR-T group (HR 1.25, 95% CI: 0.94–1.67, p=0.131). Septic shock was uncommon and similar between arms (HR 0.60, 95% CI: 0.24–1.46, p=0.250). Pneumonia was less common after CAR-T (HR 0.43, 95% CI: 0.23–0.81, p=0.007), rates of CMV infection, candidemia, and aspergillosis were low and not significantly different.

The incidence of myelodysplastic syndrome (HR 1.26, 95% CI: 0.21–7.55, p=0.799) and acute myeloid leukemia (HR 0.90, 95% CI: 0.29–2.78, p=0.850) did not differ significantly. Fatigue was less frequent after CAR-T (HR 0.40, 95% CI: 0.20–0.80, p=0.008). The incidence of end-stage renal disease was rare and similar across cohorts.

Conclusions: In this large, propensity-matched analysis of elderly RRMM patients, CAR-T therapy was associated with improved overall survival but a higher risk of hospitalization, CRS, neurotoxicity, and cytopenias compared to bispecific antibodies. CAR-T recipients had a greater incidence of hypogammaglobulinemia, yet lower rates of pneumonia and fatigue. No significant differences were observed for secondary hematologic malignancies or severe infections. Our results help guide treatment decisions as the use of immunotherapies expands in older adults with multiple myeloma, but more research is needed to establish best practices and improve outcomes.

LL&M

New York, New York