Mitigating and managing infection risk in adults treated with CAR T-cell therapy

Abstract

Chimeric antigen receptor T-cell therapy (CAR-T) has transformed the treatment paradigm of relapsed/refractory B-cell malignancies. Yet, this therapy is not without toxicities. While the early inflammation-mediated toxicities are now better understood, delayed hematopoietic recovery and infections result in morbidity and mortality risks that persist for months following CAR-T. The predisposition to infections is a consequence of immunosuppression from the underlying disease, prior therapies, lymphodepletion chemotherapy, delayed hematopoietic recovery, B-cell aplasia, and delayed T-cell immune reconstitution. These risks and epidemiology can vary over a post-CAR-T timeline of early (<30 days), prolonged (30-90 days), or late (>90 days) follow-up. Antibacterial, antiviral, and antifungal prophylaxis; growth factors and stem cell boost to expedite count recovery; immunoglobulin replacement therapy; and possibly revaccination programs are important prevention strategies to consider for infection mitigation. Assessment of risk factors, evaluation, and treatment for pathogen(s) prevalent in a particular time frame post-CAR-T are important clinical considerations in patients presenting with clinical features suggestive of infectious pathology. As more data emerge on the topic, personalized risk assessments to inform the type and duration of prophylaxis use and planning interventions will continue to emerge. Herein, we review our current approach toward infection mitigation while recognizing that this continues to evolve and that there are differences among practices stemming from data availability limitations.

Graphical abstract

Figure 1.

Risk factors for infections in the various time frames following CAR T-cell infusion.

Figure 2.

Estimated range of % of patients who develop infections over time with CD19-directed and BCMA-directed CAR T-cells (recognizing variations in reporting and criteria used) derived from refs. ^,,,,, *Data in BCMA-CAR-T recipients are limited.

Figure 3.

Dominant pathogen risk over the post-CAR-T timeline. *Fading boxes for the same pathogen over time suggest a lower risk of the pathogen in that time frame. **If a pathogen is not included in a time frame, it suggests that the risk is lower (not absent). Clinical consideration should be made as appropriate. ^#High-risk factors considered for invasive mold infection include prolonged severe neutropenia, recent BMT, prolonged use of steroids, and use of BTK inhibitors.