An article appearing in the journal Therapeutic Advances in Infectious Disease called for research to explore the infectious complications of chimeric antigen receptor (CAR) T-cell therapy and methods to prevent them.
Various CAR T-cell therapies have been approved by the U.S. Food and Drug Administration and other governing bodies for use in the treatment of diffuse large B-cell lymphoma, acute lymphoblastic leukemia, mantle cell lymphoma, and multiple myeloma, with very successful results. The field is also expanding into other disease states, such as autoimmune diseases and viral infections.
However, off-target effects are common, such as cytokine release syndrome, neurotoxicity, and immune suppression. In patients receiving CAR T-cell therapy, immunosuppression often causes neutropenia; serious bacterial and viral infections; and, less commonly, fungal infections and cytomegalovirus reactivation. Infectious complications are a significant cause of morbidity and mortality.
“The incidence of therapy-related toxicity is high and contributes to patient morbidity,” wrote the authors, led by Adam Stewart of the Centre for Clinical Research at the University of Queensland in Australia. “Infectious complications are similarly high and can potentially be mitigated by prevention strategies, including antimicrobial prophylaxis, intravenous immune globulin, and early vaccination.”
However, they argued, although many institutions have internal guidelines to guide decision-making regarding strategies to prevent infections, those standards are not supported by robust evidence. Rather, they are based on expert opinion and based on experience with other patient groups, not necessarily patients on CAR T-cell therapy. They called for research to establish evidence-based standards specifically in this patient population.
“High-level data are lacking on short and long infectious complications and how best to prevent them,” the authors concluded. “Targeted research addressing critical questions pertaining to patient outcomes is needed in order to provide optimal care.”