Fungal Infections Rarer, Linked With Worse Prognosis in Patients Receiving CAR T-Cell Therapy

While more rare than viral infections, fungal infections carry a higher risk of death for patients with blood cancers being treated with chimeric antigen receptor (CAR) T-cell therapy, researchers found.

The study, drawing on data from the World Health Organization’s global database of individual case safety reports, called VigiBase, included 3000 patients receiving axicabtagene ciloleucel and tisagenlecleucel.

The study found that fungal infections occurred at a lower rate than viral infections (22.49% vs 41.46%, respectively), though they were associated with a significantly poorer prognosis (reporting odds ratio [ROR] = 4.39; 95% CI, 1.63–12.47; P = .004). Mixed infections were also associated with a poorer prognosis compared with viral infections (ROR = 4.67; 95% CI, 2.26–10.68; P < .001).

Overall, infections occurred in 18.42% of cases and typically occurred within the first month, significantly dropping from then on. Most were controllable, with 4.4% of cases being fatal. The researchers noted that the risk of overall infection identified in their study is in line with previous research and that infection, often occurring with cytokine release syndrome (CRS), is one of the most common complications associated with CAR T-cell therapy.

“Due to CRS, prolonged cytopenia and B-cell aplasia with associated hypogammaglobulinemia, patients with CAR-T cell therapy are athigh risk of infection, therefore, antimicrobial prophylaxis is recommended,” described the researchers. "For infection prophylaxis for patients undergoing anti-CD-19 CAR-T therapy, levofloxacin (while patients are neutropenic), fluconazole/micafungin, trimethoprim-sulfamethaxazole (or pentamidine ifallergic) and acyclovir/ valacyclovir for ≥3 months were recommended for gram-negative bacteria, candida species, pneumocystis jiroveci andherpes simplex virus and varicella zoster virus, respectively.”

Data also showed that that prognostic differences were apparent between the 2 treatments. Compared with axicabtagene ciloleucel, tisagenlecleucel had a higher risk of infection (ROR = 1.76; 95% CI, 1.46-2.12; P < .001), which also translated into a poorer prognosis (ROR = 1.49; 95% CI, 1.01–2.21, P = .04).The median time of infection was shorter for axicabtagene-ciloleucel than for tisagenlecleucel.

Overall, the most common bacterial infections, which occurred in 60.7% of patients, were staphylococcal infection and Clostridium difficile infection, particularly in patients with neutropenia. The most common viral infections were rhinovirus and cytomegalovirus, and the most common fungal infection was candida infection.

“Considering the data were mainly extracted from the public database, this retrospective study has its limitations as each patient’s data integrity was inconsistent. This study only analyzed CAR-T cell products targeting CD19 (target B cells), but did not analyze other targets, such as CD7 (can target T cells), BCMA (target plasma cells), etc,” noted the researchers. “Thus, conclusions of this study may not apply to all CAR-T therapies. Another limitation is that we don’t pull out information for all VigiBase patients treated with chemotherapy for NHL and ALL as a more relevant comparison group. The VigiBase reporting system has obvious limitations in terms of reporting bias and time. This limits our abilityto report on later infections.”

Reference

Zhou L, Yin E, Zhao H, Ding S, Hu Y, Huang H. Infections in hematologic malignancy patients treated by CD19 chimeric antigen receptor T-cell therapy. ImmunoMedicine. Published online July 17, 2022. doi:10.1002/imed.1036