Introduction: Multiple myeloma (MM) is a bone marrow malignancy that predominantly involves older adults. CAR-T is a highly effective immunotherapy approved for use in patients with relapsed/refractory MM (RRMM). However, patients are at an increased risk of infection and deaths related to it due to the prolonged immunosuppression following CAR-T. This raises the question of their safety in older adults in the real-world setting.

Methods: We conducted a retrospective study of patients with RRMM treated at our institution with B-Cell Maturation Antigen CAR-T between October 2021 and April 2025. The primary endpoint of this study was the density of overall infections, as well as by infection by organism type (bacterial, viral, or fungal) within 100 days post-CAR-T. Infection density was estimated as the number of infections per 100 person days at risk. Additional endpoints included the cumulative incidence of infections, infection-related mortality, response rates, progression-free survival (PFS), and overall survival (OS). Baseline variables are reported descriptively, with medians and ranges for continuous variables and frequencies and percentages for categorical variables. The Kaplan-Meier method was used to describe survival outcomes. Univariable Cox proportional hazard regression models were used to identify factors associated with the risk of progression or death.

Results: Forty patients aged 65 years and above received CAR-T between 2021 and 2025. Of those, 62.5% were male and 85% were Caucasian. The median age at infusion was 72.3 years [range, 66.3-83.3]. The majority had a good performance status [ECOG 0-1, 94.8%], and it was maintained at 3-month follow-up. Prior to CAR-T, 25% of the patients had a comorbidity index of 5 or higher. High-risk cytogenetics were seen in 25% of patients. R-ISS at diagnosis was 1 in 11 (34.3%), 2 (16; 50%), 3 (5; 5.6%) and missing in 8 (20%) patients. The overall response rate was 75% [95% CI, 59-87]. Infections developed in 9 (22.5%) patients within 100 days post-infusion with an infection density of 0.28 per 100 patient-days [95% CI: (0.14, 0.49)]. The 30-day, 60-day, and 90-day cumulative incidence of infection were 7.5%, 15%, and 20%, respectively. Proportions of bacterial and viral infections within 100 days of CAR-T were 3 (7.5%) and 5 (12.5%), respectively, with corresponding infection densities of 0.08 and 0.14 per 100 patient-days. From the start of infusion until 1 year, 15/40 (37.5%) had at least one episode of infection, with 11/40 (27.5%) diagnosed after 100 days of CAR-T.

Total number of infections (after 100 days, within 1 year) was 21: 6 bacterial, 2 fungal, 13 viral. With a median follow-up of 11.6 months (range:1.9-38.8), 9 (22.5%) patients died, with infection as the cause of death in only 2 cases (5%). CR was seen in 33 (82.5%) patients. CRS grade 2 or higher was seen in 11 (27.5%) patients. ICANS was seen in 10 (25%) patients, but it was grade 2 or higher in only 2 (5%) patients. Half the patients had no rehospitalizations within 100 days of CAR-T (19; 47.5%). Ten patients (25%) had at least one hospitalization after discharge. Only two patients required skilled nursing facility placement following CAR-T. At the 2-year follow-up, the median PFS in the entire cohort was 1.44 years [95% CI = 0.67-Not reached (NR)], with 1- and 2-year PFS estimates of 55% (95% CI = 38%-79 %) and 33% (95% CI = 15%-74%), respectively. Similarly, the median OS in the entire cohort was NR (95% CI = 1.2- NR), with 1- and 2-year OS estimates of 80% (95% CI = 65%-98 %) and 61% (95% CI = 42%-88%), respectively. The type of CAR-T product, platelet count, and serum calcium before CAR-T were found to be significant prognostic factors for PFS. Age at CAR-T, high-risk cytogenetics, and comorbidity Index were marginally significant risk factors for PFS. Only age at CAR-T was found to be a significant risk factor for OS.

Discussion: CAR-T is safe even in older adults with RRMM. There is a significant incidence of infections with the use of cellular therapy in these patients due to suppressed humoral and cellular immunity. However, safe outcomes can be achieved with close monitoring beyond 3 months, timely diagnosis of infection, and effective antimicrobial therapy.

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2025
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