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

One of the most clinically significant complications following chimeric antigen receptor (CAR) T-cell therapy is 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, emerging real-world data indicate that vulnerability can extend well 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 postinfusion care.

Why Patients Who Receive CAR T-Cell Are Uniquely Vulnerable

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

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

CAR T-cell–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, yet clinically important, phase-based pattern.^1,2 Early infections (≤ 30 days post infusion) are most frequently bacterial in origin, including bloodstream infections, pneumonia, and catheter-related infections. However, viral reactivation, such as herpes simplex virus 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

Beyond 100 days, persistent immune dysregulation—particularly 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 clinical trials and real-world data sets, infectious complications have consistently emerged as a major adverse effect category following CAR T-cell therapy, alongside CRS and ICANS.^1-3 Although CRS and ICANS dominate early toxicity–monitoring frameworks, infections remain a frequent and clinically meaningful contributor to postinfusion 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) frequently develop infections alongside prolonged cytopenias and hypogammaglobulinemia; this underscores 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.

Although CRS and ICANS dominate acute toxicity management, infectious complications often define the postacute recovery phase and contribute substantially to morbidity and health care 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. Hill JA, Li D, Hay KA, et al. Infectious complications of CD19-targeted chimeric antigen receptor–modified T-cell immunotherapy. Blood. 2018;131(1):121-130. doi: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. Hematol Oncol. 2019;37(S1):48-52. doi: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 Jr, Shah N, et al. (2021). Idecabtagene vicleucel in relapsed and refractory multiple myeloma. New Engl J Med. 2021;384(8):705-716. doi:10.1056/nejmoa2024850