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CAR T Cell Tx and Long Term AEs
CAR T-Cell Therapy: What Oncology Nurses Need to Know About Long-Term AEs

Released: December 17, 2025

Beth Faiman
Beth Faiman, PhD, MSN, APN-BC, AOCN, BMTCN, FAAN, FAPO
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Key Takeaways
  • CAR T-cell therapy is an important option for many patients with hematologic malignancies, with the potential to improve overall patient outcomes.
  • Although short-term adverse events (AEs) occur while patients are in the care of CAR T-cell treatment centers, oncology nurses in community practices often encounter late cytopenias, infections, neurologic symptoms, or gastrointestinal complaints.
  • Care plans are central to long-term safety. Instructions for monitoring, appropriate prophylaxis, early recognition of delayed AEs, and clearly written AE management instructions are key to safe, equitable long-term care.

Current and Evolving Role of CAR T-Cell Therapy
In less than a decade, CAR T-cell therapy has evolved from a last-resort option for highly refractory disease to a standard treatment for B-cell acute lymphoblastic leukemia (B-ALL), large B-cell and other non-Hodgkin lymphomas, mantle cell lymphoma, and relapsed/refractory (R/R) multiple myeloma (MM). For example, although BCMA-directed CAR T-cell therapies ciltacabtagene autoleucel (cilta-cel) and idecabtagene vicleucel (ide-cel) were first FDA approved in patients with R/R MM after 4 or more prior lines of therapy, the indications were expanded to earlier-line use based on clinical outcomes from the pivotal phase III CARTITUDE-4 (after 1 or more prior line of therapy with cilta-cel) and KarMMa-3 (after 2 or more prior lines of therapy with ide-cel) trials, which demonstrated deeper responses and superior progression-free survival (PFS) vs standard regimens.

Regulatory guidance has also evolved. In January 2024, the FDA issued a class-wide boxed warning for all approved CD19- and BCMA-directed CAR T-cell products to highlight the serious risk of secondary T-cell malignancies. In June 2025, the FDA removed the Risk Evaluation and Mitigation Strategies (REMS) for all currently approved CD19- and BCMA-directed autologous CAR T-cell products. For ide-cel and lisocabtagene maraleucel, the FDA shortened the requirement for patients to stay within close proximity to a healthcare facility from 4 weeks to 2 weeks and reduced postinfusion driving restrictions from 8 weeks to 2 weeks, reflecting growing real-world experience with toxicity monitoring. Subsequently, in October 2025, cilta-cel received an additional boxed warning for immune effector cell–associated enterocolitis (IEC-EC) after postmarketing reports of severe, sometimes life-threatening diarrhea, abdominal pain, weight loss, gut perforation, and sepsis occurring weeks to months after infusion. Collectively, these changes underscore that long-term toxicity monitoring can no longer reside solely at the CAR T infusion center: oncology nurses in community practices are increasingly becoming the first to encounter late cytopenias, infections, neurologic symptoms, or gastrointestinal complaints.

Current Use of CAR T-Cell Therapies: Patient Selection and Short-Term Care
CD19-directed CAR T-cell therapies like axicabtagene ciloleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, and tisagenlecleucel are used for R/R B-ALL, diffuse large B-cell and related lymphomas, mantle cell lymphoma, and some follicular lymphomas. Obecabtagene autoleucel is currently approved solely for adults with R/R B-cell precursor ALL; brexucabtagene autoleucel is also approved for this indication. BCMA-directed products like cilta-cel and ide-cel are used for R/R MM. Eligibility for CAR T-cell therapy is driven more by functional status, organ function, kinetics of disease progression, and social support than by chronologic age; active infection, uncontrolled CNS disease, or lack of a reliable caregiver are common contraindications.

A successful patient journey begins with early referral, eligibility assessment, and T-cell collection, followed by a 3- to 4-week manufacturing period during which “bridging” therapy may be needed to control disease while preserving T-cell fitness. Immediately before infusion, patients receive lymphodepleting chemotherapy. The infusion itself is brief, but during the subsequent 1-2 weeks, the patient is at increased risk for developing acute toxicities such as cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Thus, close monitoring and rapid access to inpatient care, even when infusion occurs in an outpatient setting, are required. Recent regulatory changes, including the elimination of REMS and shortened driving/proximity restrictions for some products, help reduce logistical burdens, but nurses still need to individualize care according to each patient’s neurotoxicity risk, caregiver and housing support, and other factors.

CRS typically occurs within the first week after infusion, with ICANS often overlapping with or following CRS. Hyperinflammatory syndromes such as hemophagocytic lymphohistiocytosis/macrophage activation syndrome are less common than CRS but can be life threatening and often accompany severe CRS. Nurses should be alert to persistent high fevers, rapidly rising ferritin levels, liver dysfunction, and coagulopathy that do not improve with standard CRS-directed therapy. It is important to note that inflammatory toxicities and infections frequently overlap. Roughly 1 in 4 CAR T-cell recipients develop an infection in the first 30 days, with bacterial infections predominating early and viral infections peaking after the first month. This means that any febrile CAR T-cell recipient should be evaluated for both CRS and sepsis in parallel: obtain cultures and begin empiric antibiotics promptly, even as tocilizumab and/or corticosteroids are started according to institutional CRS guidelines.

Long-Term Toxicities: What Nurses Need to Monitor Postinfusion
Once patients leave the CAR T-cell treatment center, the adverse event profile shifts toward longer-term cytopenias, infections, immune dysregulation, and organ-specific complications—the very issues community oncology nurses are expected to manage.

Immune Effector Cell–Associated Hematotoxicity
Every CAR T-cell recipient is at risk for long-term toxicities. Cytopenias often outlast the acute CRS/ICANS window. Such prolonged or biphasic cytopenias are now recognized as immune effector cell–associated hematotoxicity (ICAHT). The European Hematology Association and European Society for Blood and Marrow Transplantation consensus recommendations outline grading based on the duration and severity of neutropenia, anemia, and thrombocytopenia and emphasize their strong association with infections and transfusion needs.

Risk factors for ICAHT include a high disease burden, extensive prior therapy (including hematopoietic stem cell transplantation), and baseline cytopenias. From a nursing standpoint, key actions in the community include: 

  • Ensuring a standing order set for complete blood count monitoring at least weekly for the first 1-3 months, then appropriately spaced based on recovery;
  • Advocating for G-CSF in patients with prolonged neutropenia when not contraindicated and for transfusion support per institutional thresholds; and
  • Maintaining a low threshold to treat fever or localized symptoms as potential neutropenic infections, even months after infusion.

Hypogammaglobulinemia and Infections
On-target/off-tumor effects on normal B-cells (or plasma cells) cause many patients to develop B-cell aplasia and hypogammaglobulinemia. IgG, IgA, and IgM levels can remain low for a year or longer and clearly contribute to late bacterial and viral infections. To prevent infections, the American Society for Transplantation and Cellular Therapy (ASTCT) 2024 “Best Practice Considerations” recommend herpes simplex virus/varicella zoster virus prophylaxis (eg, acyclovir or valacyclovir) for at least 6 months post infusion and longer if immunosuppression continues; Pneumocystis jirovecii pneumonia prophylaxis for at least 6 months post CAR T-cell therapy; antibacterial prophylaxis during prolonged neutropenia (when absolute neutrophil count <500/µL and continued until neutrophil recovery); targeted antifungal prophylaxis for patients at high risk; and HBV antiviral prophylaxis and monitoring for patients with surface antigen or core antibody positivity. Immunoglobulin replacement remains individualized, but many centers monitor IgG levels monthly for the first 6 months and every 3 months until 1 year and consider IVIG when IgG levels are <400 mg/dL and/or infections are recurrent, continuing into the second year as needed. Community nurses are central to this approach by tracking immunoglobulin levels, CD4 counts, and infection history and by prompting timely discussions about IVIG and adjusting or extending prophylaxis for patients with persistent immune deficits.

Revaccination and Vaccines for Family and Caregivers
Because CAR T-cell recipients often lose protection from prior vaccines, international and ASTCT guidance generally treats these individuals as “functionally unvaccinated” and recommends restarting inactivated vaccines (eg, influenza, COVID-19, pneumococcal, Tdap) beginning around 3 months after CAR T-cell infusion, once acute toxicities have resolved and blood counts are recovering. Live vaccines, if used at all, are reserved for carefully selected patients at least 24 months after CAR T-cell infusion who have good immune reconstitution. Household contacts should be up to date on routine vaccines, including inactivated influenza and COVID-19, while avoiding live intranasal influenza and oral polio vaccines because of the risk of prolonged viral shedding and transmission. Community nurses can normalize revaccination as a standard part of care, coordinate with primary care or infectious disease colleagues, and tailor schedules to each patient’s pace of immune recovery.

Delayed Neurologic and Movement Disorders
Most cases of ICANS occur within the first 2 weeks, but delayed neurologic events, including movement and gait disorders, cranial neuropathies (eg, Bell’s palsy), and subtle cognitive changes, are increasingly recognized after CAR T-cell therapy, particularly with BCMA-directed cilta-cel in R/R MM. Movement changes such as difficulty holding a glass or ataxia are red flags that caregivers often notice first. Community nurses can efficiently screen for movement disorders by asking about handwriting, balance, facial asymmetry, and new tremors and by actively seeking caregiver observations; any new neurologic symptom in the first year after CAR T-cell therapy—especially after cilta-cel—should prompt immediate contact with the treating center and an expedited neurologic evaluation

Transitioning Care: From the CAR T-Cell Treatment Center to the Community
Successful outcomes following CAR T-cell therapy depend on a clear, shared transition plan between the treatment center, the community oncology team, and the patient. A concise post–CAR T-cell infusion care plan sent to the community team and given to the patient should, at minimum, outline the product (target, indication, infusion date), key elements of lymphodepletion and bridging therapy, a brief summary of any acute adverse events that were experienced (such as CRS or ICANS) and how they were managed, current prophylactic medications with stop criteria, recommended lab monitoring (CBC, chemistries, immunoglobulin levels, CD4 counts) with thresholds for growth factors and transfusions, the revaccination plan, and 24/7 contact information for the CAR T-cell treatment center. Wallet cards that list the specific CAR T-cell product used, infusion date, major toxicity concerns (eg, CRS, ICANS, IEC-EC for cilta-cel), and symptoms that require urgent attention remain a simple but critical tool for both patients and healthcare professionals.

Equity and access considerations should be built into every transition plan. Even with the removal of REMS and shorter monitoring restrictions, many patients still face long travel distances, financial strain, and/or caregiver burden. Nurses are often the first to recognize barriers such as lack of transportation, caregiver burnout, or difficulty taking time off work. Healthcare professionals can help mitigate these barriers by leveraging standardized checklists, telehealth touchpoints, and financial navigation and by connecting patients with social workers, patient assistance programs, and nonprofit resources.

Your Thoughts
How are you adapting your referral, education, and follow-up processes as CAR T-cell therapies move earlier in the treatment landscape and ensuring timely recognition of both acute and long-term toxicities? Get involved in the discussion by posting a comment below.

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