Incidence of Invasive Fungal Infections Following BCMA-Directed CAR T-Cell Therapy in Multiple Myeloma

Patients with multiple myeloma (MM) treated with B-cell maturation antigen (BCMA)-targeting chimeric antigen receptor (CAR) T-cell therapy show a discernible risk in the cumulative incidence of invasive fungal disease (IFD). The data were presented at IDWeek 2025 in Atlanta.

Patients with MM face an increased risk of infections due to both the disease’s immunosuppressive nature and the effects of intensive therapies used in treatment. Among these therapies, BCMA-directed CAR T-cell therapy has revolutionized care for relapsed or refractory MM, offering durable responses in patients who have exhausted other options. However, as this powerful therapy expands in use, questions remain regarding its infectious complications—particularly invasive fungal diseases (IFDs), which can lead to severe morbidity and mortality.

To better understand the burden of fungal infections following BCMA-directed CAR T-cell therapy, researchers conducted a systematic review and meta-analysis of published studies. The analysis aimed to estimate the pooled cumulative incidence of IFDs, including invasive aspergillosis and invasive candidiasis, among patients treated with these novel cellular therapies.

Investigators searched PubMed and EMBASE databases for studies involving patients with MM who received BCMA-directed CAR T-cell therapy and reported infection outcomes. After screening 232 citations, studies were excluded if they lacked data on infectious complications or if patient follow-up was shorter than 30 days. Ultimately, 9 studies were identified that met inclusion criteria for IFD incidence, providing a comprehensive view across diverse clinical settings and CAR T-cell constructs.

Across these 9 studies, data from 823 patients were analyzed. Among them, 31 patients developed an IFD, corresponding to a pooled cumulative incidence of 3.19% (95% CI, 1.86–4.79). When stratified by infection subtype, the incidence of invasive aspergillosis was 1.22% (95% CI, 0.21–2.77) based on 7 studies encompassing 515 patients, while invasive candidiasis occurred in 0.51% (95% CI, 0.00–1.67) of 515 patients across the same number of studies. These findings highlight that although IFDs are relatively uncommon following BCMA-directed CAR T-cell therapy, they represent a clinically meaningful risk given the vulnerable nature of this patient population.

The pathogenesis of infection in this setting is multifactorial. CAR T-cell therapy induces profound cytopenias and immune dysregulation, particularly B-cell aplasia and hypogammaglobulinemia, which can persist for months following treatment. Additionally, patients often receive corticosteroids or tocilizumab for cytokine release syndrome management, further compounding infection risk. The data underscore the importance of vigilant infection monitoring, prophylactic strategies, and early intervention in managing potential IFDs.

As the first meta-analysis to quantify the incidence of invasive fungal infections among patients with MM receiving BCMA-directed CAR T-cell therapy, this study establishes a valuable benchmark for future research. The results suggest that while IFDs remain relatively infrequent, their potential severity warrants heightened clinical awareness and further investigation.

Prospective studies are needed to better define patient- and treatment-related risk factors, guide antifungal prophylaxis decisions, and improve infection outcomes in this growing population of CAR T-cell recipients.

REFERENCES

Vassilopoulos S, Vassilopoulos A, London A, et al. (P-2160) Cumulative incidence of invasive fungal disease among patients with multiple myeloma who received B-cell maturation antigen–directed CAR T-cell therapy: A systematic review and meta-analysis. Presented at: IDWeek25. 10/19-10/22. Atlanta, Georgia. Abstract P-2160