Incidence of Invasive Fungal Infections in CAR T-Cell Therapy Recipients: A Single-Center Retrospective Analysis

Background CAR T therapy has transformed hematologic malignancy treatment, yet challenges persist like cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and infections. Invasive fungal infections (IFI) rates post CAR T range 1-7%. Some centers use fungal biomarkers [(1–>3)-β-D-glucan (B-DG) and galactomannan (GM)] and imaging for preemptive fungal therapy. We assessed diagnostic performance of surveillance B-DG and GM for IFI diagnosis in CAR T recipient. Methods We retrospectively analyzed adult patients (pts) who received BCMA and CD19 CAR T therapy for multiple myeloma (MM) and non-Hodgkin lymphoma (NHL) from 2018-2023. IFI followed EORTC/MSG criteria (PMID: 31802125), with inclusion limited to proven or probable infections. Antifungal prophylaxis was per physician's discretion. Monitoring occurred pre-apheresis, pre-infusion, and every 14 days for 6 months (mon). Cumulative incidence was calculated, considering time to IFI, with IFI-free death and disease relapse as competing risks. We used SPSS (version 29.0). Result Of the 148 subjects, 51 pts (34.5%) received BCMA CAR T, and 97 (65.5%) received CD19 CAR T therapy. The BCMA cohort had more prior therapies (median 6 vs. 4 in CD19), a higher rate of prior autologous stem cell transplantation (84% vs. 15% in CD19).In the BCMA cohort, CRS rates were 90% (22% grade 2-4), while ICANS rates were 12% (8% grade 2-4). In the CD19 cohort, CRS rates were 88% (30% grade 2-4), with ICANS rates at 44% (25% grade 2-4).The median follow-up from CAR T infusion was 9.5 mon (range 0-63) in both cohorts, with 12 mon (range 0-63) in the BCMA and 8 mon (range 0-49) in the CD19 cohort.All pts received antifungal prophylaxis: anti-yeast (fluconazole, n=95) and anti-mold (micafungin n=5, isavuconazole n=1, or posaconazole n=52). In the BCMA cohort, 92% received anti-yeast, 8% anti-mold prophylaxis. In the CD19 cohort, 49.5% received anti-yeast, 50.5% anti-mold prophylaxis.Among the pts, 14% had elevated B-DG levels, and only 1% showed elevated GM levels. However, most of these cases (95%) turned out to be false positives, due to IVIG administration accounting for 60% of them.Only one pt in CD 19 cohort developed IFI, resulting in a 1-year Cumulative incidence of 0.7% (95% confidence interval [CI], 0- 2.1). This pt received anti-yeast prophylaxis and had a disseminated Rhizopus infection, leading to death.Median PFS in the overall: 11.7 mon (95% CI, 6.9-16.6), BCMA cohort: 8.6 mon (95% CI, 3.2-13.97), CD19 cohort: 14.6 mon (95% CI, not reached (NR)-NR) (p=0.324). OS in the overall: 32.4 mon (95% CI, 16.3-48.4), BCMA cohort: 41.4 mon (95% CI, 16.74-66.08), CD19 cohort: 23.98 mon (95% CI, NR-NR) (p=0.260). Conclusion The rate of IFI in our cohort was low (0.7%) post-CAR T therapy. The diagnostic performance of serial monitoring of B-DG and GM for the diagnosis of IFI is poor in BCMA and CD19 CAR T therapy.