Infection Risk After CAR-T Therapy: An Underrecognized but Persistent Threat in the Post-Infusion Window

One of the most clinically significant complications following chimeric antigen receptor T-cell (CAR-T) cell therapy remains infection, with reported infection rates ranging from approximately 45% to 72% across data.^1,2 Clinical attention is often centered on cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS); however, infectious complications continue to contribute substantially to morbidity, hospital readmissions, and prolonged recovery following infusion.^2,3

The highest risk period occurs within the first 30 days post-infusion; however, developing real-world data indicates vulnerability can extend far beyond the acute treatment window, particularly in patients with persistent cytopenias and hypogammaglobulinemia.^1,2 As CAR-T cell therapy use expands into earlier lines of therapy and broader patient populations, infection prevention has become a focal point of post-infusion care.

Why CAR-T Patients Are Uniquely Vulnerable

CAR-T–associated immune dysfunction differs fundamentally from conventional chemotherapy-induced immunosuppression in both structure and duration. Rather than a single, time-limited nadir in immune function, CAR-T cell therapy produces a layered pattern of immune disruption that evolves across multiple phases of treatment and recovery.^1,2

Early immune suppression is driven mainly through lymphodepleting chemotherapy, which induces predictable neutropenia in the peri-infusion period. However, immune recovery does not follow a standard post-chemotherapy trajectory. In many patients, cytopenias persist beyond the acute phase, contributing to sustained impairment in innate immune defenses.^2,3

CAR-T–mediated B-cell aplasia results in prolonged hypogammaglobulinemia, further weakening humoral immunity and increasing susceptibility to both typical and opportunistic infections.^1,3 This combination of early myeloid suppression and prolonged adaptive immune dysfunction creates a distinctly biphasic and often prolonged infection risk profile compared with traditional cytotoxic chemotherapy alone.^1-3

When Infections Occur and Why It Matters

Infections following CAR-T cell therapy tend to follow a predictable but clinically important phase-based pattern.^1,2 Early infections (≤30 days post-infusion) are most frequently bacterial in origin; this includes bloodstream infections, pneumonia, and catheter-related infections, while viral reactivation such as HSV and cytomegalovirus may also occur in the setting of lymphodepletion and acute cytopenias.^2,3

During the intermediate period (30–100 days post-infusion), patients remain immunologically vulnerable despite recovery from acute toxicities, and opportunistic infections become more prominent, including varicella-zoster virus reactivation and, in select high-risk populations, fungal infections.^3,4

Exceeding 100 days, long-term immune dysregulation—particularly persistent hypogammaglobulinemia and delayed immune reconstitution—can sustain infection risk well into survivorship.^1,3 Among current data, overall infection rates following CAR-T cell therapy commonly exceed 30% to 50%, which demonstrates that infectious complications are not rare events but expected outcomes requiring structured prophylaxis and monitoring.^2,4

Evidence Across CAR-T Products

In vital clinical trials and real-world datasets, infectious complications are consistently emerging as a major category of adverse effects following CAR-T cell therapy, occurring alongside CRS and ICANS.^1-3 While CRS and ICANS dominate early toxicity monitoring frameworks, infections remain a frequent and clinically meaningful contributor to post-infusion morbidity and hospitalization.

In CD19-directed therapies such as lisocabtagene maraleucel (Breyanzi, Juno Therapeutics, Inc.), infections have been reported across both early and extended follow-up periods, with risk influenced by baseline disease burden, prior lines of therapy, and the trajectory of immune reconstitution following infusion.⁴

Similarly, in relapsed/refractory multiple myeloma, patients treated with idecabtagene vicleucel (Abecma, Bristol Myers Squibb), infections are frequently observed alongside prolonged cytopenias and hypogammaglobulinemia; this reinforces the importance of structured antimicrobial prophylaxis and long-term immune monitoring in this population.⁵

Why This Matters Now

CAR-T cell therapy is no longer confined to late-line, highly selected patients, as its use continues to expand into earlier lines of therapy across both lymphoma and multiple myeloma indications.^1,2 As patient eligibility broadens, infection risk management is increasingly shifting from a tertiary oncology concern to a core component of standard hematology and pharmacy practice.

While CRS and ICANS dominate acute toxicity management, infectious complications often define the post-acute recovery phase and contribute substantially to morbidity and healthcare utilization.^2,3

This evolution represents a growing opportunity to standardize antimicrobial prophylaxis, optimize monitoring strategies, and close persistent gaps in long-term supportive care within a rapidly expanding cellular therapy landscape.^1-3

REFERENCES

1. Joshua A. Hill, Daniel Li, Kevin A. Hay, Margaret L. Green, Sindhu Cherian, Xueyan Chen, Stanley R. Riddell, David G. Maloney, Michael Boeckh, Cameron J. Turtle; Infectious complications of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy. Blood 2018; 131 (1): 121–130. doi: https://doi.org/10.1182/blood-2017-07-793760

2. Xia Y, Zhang J, Li J, et al. Cytopenias following anti-CD19 chimeric antigen receptor (CAR) T cell therapy: a systematic analysis for contributing factors. Ann Med. 2022;54(1):2951-2965. doi:10.1080/07853890.2022.2136748

3. Neelapu SS. Managing the toxicities of CAR T-cell therapy. Hematological Oncology. 2019;37(S1):48–52. https://doi.org/10.1002/hon.2595

4. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. Lancet. 2020;396(10254):839-852. doi:10.1016/S0140-6736(20)31366-0

5. Munshi NC, Anderson LD, Shah N, et al. (2021). Idecabtagene Vicleucel in Relapsed and Refractory Multiple Myeloma. New England Journal of Medicine, 384(8), 705–716. https://doi.org/10.1056/nejmoa2024850