# 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

## TL;DR

This study finds that patients with multiple myeloma who receive BCMA-directed CAR T-cell therapy face a notable risk of invasive fungal diseases, including aspergillosis and candidiasis.

## Contribution

This is the first meta-analysis to evaluate the incidence of invasive fungal disease in multiple myeloma patients receiving BCMA-directed CAR T-cell therapy.

## Key findings

- The cumulative incidence of invasive fungal disease (IFD) was 3.19% among 823 patients.
- Invasive aspergillosis occurred in 1.22% of patients receiving BCMA-directed CAR T-cell therapy.
- Invasive candidiasis had a cumulative incidence of 0.51% in the studied patient population.

## Abstract

Patients with multiple myeloma are at higher risk for infections due to disease pathophysiology and administered therapies. The purpose of this study was to estimate the incidence of invasive fungal infections in patients with multiple myeloma who received B-cell maturation antigen (BCMA)–directed chimeric antigen receptor (CAR) T-cell therapy.Cumulative incidence rate of IFD among patients with multiple myeloma who received BCMA–directed CAR T-cell therapyCumulative incidence rate of invasive aspergillosis among patients with multiple myeloma who received BCMA–directed CAR T-cell therapy

Cumulative incidence rate of IFD among patients with multiple myeloma who received BCMA–directed CAR T-cell therapy

Cumulative incidence rate of invasive aspergillosis among patients with multiple myeloma who received BCMA–directed CAR T-cell therapy

We searched PubMed and EMBASE for studies that included patients with multiple myeloma who received BCMA–directed CAR T-cell therapy and evaluated the incidence of infections among this patient population. We present the pooled cumulative incidence of invasive fungal disease (IFD), invasive fungal aspergillosis, and invasive fungal candidiasis by performing a random-effects meta-analysis.

After screening 232 citations and excluding studies which did not report infectious complications or with a follow up of less than 30 days, we identified and analyzed studies reporting IFD, invasive aspergillosis, or invasive candidiasis among participants with multiple myeloma who received BCMA-directed CAR T-cell therapy. Specifically, we retrieved 9 studies that reported data on the development of IFD and among 823 patients who received BCMA-directed CAR T-cell therapy, we found that 31 patients developed IFD with a cumulative incidence of 3.19% (95% CI, 1.86-4.79). In addition, we retrieved 7 studies that reported data on the development of invasive aspergillosis, among 515 patients who received BCMA-directed CAR T-cell therapy 9 patients developed invasive aspergillosis with a cumulative incidence of 1.22% (95% CI, 0.21-2.77). For invasive candidiasis, we retrieved 7 studies and among 515 patients who received BCMA-directed CAR T-cell therapy 4 patients developed invasive candidiasis with a cumulative incidence of 0.51 (95% CI, 0.00-1.67).

In this first meta-analysis evaluating the incidence of IFD in patients with MM receiving BCMA-targeted CAR T-cell therapy, we found that this patient population faces a discernible burden of IFD, including aspergillosis and candidiasis. Although these infections remain relatively uncommon, considerable morbidity and mortality among this patient population supports the need for prospective studies aimed at identifying risk factors.

Eleftherios Mylonakis, MD, PhD, Chemic Labs/Koda Therapeutics, LLC: Grant/Research Support|Lumen: DSMB|NIH/NIAID: Grant/Research Support|Sciclone: Grant/Research Support|Shionogi: Advisor/Consultant|Synexis: Clinical trial