Full Title: Late-onset immune effector cell-associated colitis following ciltacabtagene autoleucel (cilta-cel) in relapsed/refractory IgA multiple myeloma
Submitted by Severine Wautier, Marie-Christiane Vekemans, Guillaume Dachy, Cliniques universitaires Saint-Luc, Brussels, Belgium
Physicians expert perspective: Severine Wautier and Guillaume Dachy, Cliniques universitaires Saint-Luc, Brussels, Belgium
Nurses expert perspective: Burcin Bilge, haematological care coordinator nurse, Cliniques universitaires Saint-Luc, Brussels, Belgium
Clinical Case Summary
A 68-year-old patient with relapsed/refractory IgA multiple myeloma in the third-line setting received ciltacabtagene autoleucel (cilta-cel). Bridging therapy with carfilzomib and dexamethasone yielded a very good partial response (VGPR). Post-infusion, the patient developed grade 1 cytokine release syndrome (CRS) between day +6 and day +10, with a peak lymphocyte expansion of 5,500 cells/µL on day +8. Prophylactic dexamethasone (10 mg twice daily) was administered to mitigate the risk of hyperlymphocytosis-associated neurotoxicity. The remainder of the acute phase was uneventful.
On day +40, the patient developed grade 3 diarrhea (8–10 bowel movements/day including 2 nocturnal episodes), accompanied by a 3 kg weight loss over three weeks. Urgent colonoscopy showed macroscopically normal mucosa; however histopathological analyses of biopsies demonstrated aspecific lymphocytic colitis. The infectious workup, including Clostridioides difficile toxin assay, parasite screening, CMV PCR on biopsy samples and stool cultures, was negative.
Which of the following is the most likely diagnosis?
A. Clostridioides difficile colitis
B. Irritable bowel syndrome
C. Immune effector cell-associated colitis (IEC-colitis)
D. New-onset inflammatory bowel disease
E. Myeloma-related gastrointestinal infiltration
A diagnosis of immune effector cell-associated colitis (IEC-colitis) was established. Treatment with methylprednisolone 1 mg/kg/day was initiated, resulting in clinical improvement to grade 1 and allowing successful corticosteroid tapering. In the event of steroid-refractory disease, second-line therapy with ruxolitinib would have been considered, based on emerging evidence from the CAR T-cell and GI-GvHD literature.
Expert Perspective by Severine Wautier & Guillaume Dachy
Background
Immune effector cell-associated colitis (IEC-colitis) is an emerging late complication of CAR T-cell therapy, distinct from the well-defined acute toxicities of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) (1). In contrast to CRS and ICANS, which usually develop within the first two weeks post-infusion, IEC-colitis generally arises after day +30, at a time when vigilance for CAR T-related complications has often waned. Although uncommon with a reported incidence of 1.2% to 4.3% across published series, IEC-colitis may result in severe and occasionally life-threatening complications (1-3). Most reported cases have occurred following treatment with anti-BCMA CAR T-cells, more specifically ciltacabtagene autoleucel.
Differential Diagnosis in the Immunocompromised Host
In any immunocompromised patient presenting with late-onset diarrhea after CAR T-cell infusion, a systematic diagnostic approach is essential. Clostridioides difficile infection should be excluded given the frequent antibiotic exposure during the peri-transplant period. CMV colitis, a potentially life-threatening complication in lymphodepleted patients, should be ruled out by mucosal PCR testing on biopsy samples, as negative serology alone is insufficient and blood PCR suffers from limited sensitivity in this context. Enteropathogenic bacterial, fungal, and parasitic infections should be investigated through stool cultures and microscopy. Overmore, drug-induced diarrhea, including antibiotic-associated dysbiosis, should also be considered. While uncommon in multiple myeloma, disease relapse with gastrointestinal involvement must be borne in mind, particularly in patients with insufficient CAR T-cell responses. Finally, new-onset irritable bowel syndrome remains a diagnosis of exclusion, while a inflammatory bowel diseases require to meet up precise diagnostic criteria.
Pathophysiology
IEC-colitis pathophysiology remains poorly understood but appears to share important features with gastrointestinal graft-versus-host disease (GI-GvHD). Both conditions involve immune-mediated injury to the intestinal epithelium driven by activated cytotoxic T lymphocytes, including expanded CAR T- and bystander T-cells. Tissue damage is mediated through direct cytotoxicity and release of pro-inflammatory cytokines, such as IFN-γ and TNF-α. Furthermore, in BCMA CAR T-cell settings, depletion of IgA-secreting plasma cells within the intestinal mucosa may also contribute to disease pathogenesis. Beyond their role in pathogen neutralization through IgA production, GI-resident plasma cells also exert local immunoregularoty functions by producing anti-inflammatory cytokines, such as IL-10. Their loss may promote dysregulated intestinal immune responses and impaired gut homeostasis (4). When atypical lymphoid infiltrates are observed, CAR T-cell staining and T-cell receptor (TCR) clonality analysis should be performed to distinguish reactive immune cell expansion from a clonal neoplastic process, including the rare possibility of CAR T-cell lymphoma (5).
Clinical Features and Diagnosis
IEC-colitis is characterized by watery, non-bloody, frequently severe (³ grade 3), and often nocturnal diarrhea. Additional manifestations include abdominal cramping pain, malnutrition and weight loss, with some patients requiring a period of parenteral nutrition (1,2). Gastroscopy and colonoscopy may be macroscopically normal, underscoring the importance of systematic biopsy sampling even in the absence of visible mucosal lesions. Histopathological findings typically demonstrate a lymphocytic or mixed inflammatory mucosal infiltrate despite a normal or only mildly inflamed endoscopic appearance, as observed in the present case. Crypt apoptosis and mucosal ulcerations have also been reported (2, 6). The diagnosis is established by histopathological evidence of lymphocytic colitis after exclusion of infectious etiologies. A low threshold for diagnostic investigation is warranted in any patient presenting with unexplained diarrhea beyond day +30 after CAR T-cell infusion.
Management
First-line treatment relies on systemic corticosteroids, typically methylprednisolone at 1-2 mg/kg/day, with dose tapering guided by clinical response. In our patient, diarrhea improved to grade 1 within 10 days, allowing initiation of a progressive corticosteroid taper. In steroid-refractory patients, ruxolitinib, a JAK1/2 inhibitor, has emerged as a second-line option, extrapolated from steroid-refractory GI-GvHD literature and supported by growing numbers of reports describing its use in CAR T-cell associated IEC-colitis (7). Other immunomodulatory agents, such as infliximab or vedolizumab, may also be considered in selected patients with corticosteroid-refractory disease (1,8).
Conclusion
This case highlights the importance of recognising IEC-colitis as a distinct and potentially underdiagnosed late complication of CAR T-cell therapy. Clinicians should promptly perform endoscopic evaluation with systematic biopsies in patients presenting with late-onset diarrhea after CAR T-cell infusion, even in absence of endoscopic lesions.
Correct Answer – C. Immune effector cell-associated colitis (IEC-colitis)
References:
1. Fortuna, Gliceida Galarza et al. “Immune effector cell-associated enterocolitis following chimeric antigen receptor T-cell therapy in multiple myeloma.” Blood cancer journal vol. 14,1 180. 16 Oct. 2024, doi:10.1038/s41408-024-01167-8
2. Susanibar-Adaniya, Sandra et al. “Immune effector cell-associated enterocolitis post-BCMA directed CAR T-cell therapy: insights from a multicenter case series.” Blood cancer journal vol. 16,1 64. 28 Apr. 2026, doi:10.1038/s41408-026-01473-3
3. Lim, Kenneth Jc et al. “Diagnosis and management of immune effector cell-associated enterocolitis (IEC-EC) following ciltacabtagene autoleucel.” Blood advances, bloodadvances.2025018853. 10 Apr. 2026, doi:10.1182/bloodadvances.2025018853
4. Lycke, N Y, and M Bemark. “The regulation of gut mucosal IgA B-cell responses: recent developments.” Mucosal immunology vol. 10,6 (2017): 1361-1374. doi:10.1038/mi.2017.62
5. Somay, Kayra et al. “Is immune effector cell-associated enterocolitis a CAR T-cell lymphoproliferative disorder?.” Blood cancer journal vol. 15,1 117. 3 Jul. 2025, doi:10.1038/s41408-025-01319-4
6. Osnis, Leah et al. “Patterns of Gastrointestinal Injury Associated With CAR-T Therapy for Patients With Multiple Myeloma.” The American journal of surgical pathology vol. 50,3 (2026): 292-300. doi:10.1097/PAS.0000000000002499
7. Blumenberg, Viktoria et al. “Ruxolitinib for ciltacabtagene autoleucel-associated refractory diarrhea.” Blood vol. 147,19 (2026): 2215-2225. doi:10.1182/blood.2025032347
8. Banerjee, Rahul et al. “Managing IEC-associated enterocolitis following CAR-T therapy in multiple myeloma.” Blood cancer journal vol. 15,1 112. 30 Jun. 2025, doi:10.1038/s41408-025-01320-x
Nurses Expert Perspective by Burcin Bilge
Introduction
The nursing management of patients undergoing CAR T-cell therapy has evolved considerably as the complexity and timeline of potential complications have expanded. While acute toxicities such as CRS and ICANS are now well integrated into nursing protocols, late-onset complications — including IEC-colitis — remain less familiar to many nursing teams and represent an important educational priority.
Early Recognition: A Nursing Responsibility
In the outpatient follow-up setting, nurses are frequently the first point of contact for patients reporting new or worsening symptoms. In this case, the patient developed grade 3 diarrhea at day +40 — a period at which patients have often returned home and may attribute gastrointestinal symptoms to dietary changes, anxiety, or residual treatment-related effects. This is particularly relevant for patients living at a significant distance from the treating centre: our patient resided approximately 100 km away, making in-person assessment neither immediate nor straightforward.
At our centre, a dedicated CAR T-cell telephone helpline is available for all patients throughout the follow-up period. In addition, patients without scheduled consultation received proactive weekly phone calls from the nursing team, ensuring continuity of monitoring regardless of geographical distance. This structured remote surveillance proved critical in this case: it was during a scheduled telephone contact that the patient first reported increased stool frequency, prompting urgent clinical evaluation and subsequent colonoscopy.
Structured nursing telephone assessment should include systematic questioning about stool frequency and consistency, nocturnal episodes, and associated symptoms such as abdominal cramping and weight loss. The use of the CTCAE grading scale for diarrhea facilitates consistent documentation and prompt escalation to the medical team.
Patient Education and Empowerment
Prior to CAR T-cell infusion and throughout the follow-up period, nurses play a central role in patient education. Patients and caregivers should be explicitly informed that complications may arise weeks after infusion, and that any new symptoms should be reported without delay, even if they appear minor. In our experience, delayed reporting of diarrhea is not uncommon among patients living far from the centre, as symptoms are often perceived as minor or self-limiting complaint. Clear written and verbal instructions on warning signs requiring medical advice — including defined thresholds such as ≥4 stools/day above baseline, nocturnal episodes, or weight loss exceeding 2 kg — can meaningfully reduce diagnostic delay, particularly in geographically remote patients.
Nursing Assessment and Monitoring During Treatment
Following IEC-colitis diagnosis and systemic corticosteroid initiation, nursing monitoring encompasses several key domains. Fluid and electrolyte balance must be closely assessed, with attention to signs of dehydration, hyponatraemia, and hypokalaemia — particularly relevant in elderly patients such as this one. Nutritional status should be monitored systematically, with early involvement of the dietitian when significant weight loss has occurred. Steroid-related side effects, including hyperglycaemia, insomnia, mood changes, and increased infection susceptibility, require structured assessment and proactive patient communication. In patients receiving ruxolitinib as second-line therapy, nurses should be aware of specific monitoring requirements, including regular full blood count surveillance and heightened vigilance for opportunistic infections.
Psychological and Supportive Care Dimensions
Beyond physical symptoms, grade 3 diarrhea has a significant impact on quality of life, autonomy, and psychological wellbeing. In particular, nocturnal episodes may cause profound sleep disturbance, social withdrawal, and anxiety. For patients living at a distance from the centre, combination of physical symptoms and geographical isolation can amplify distress. Nurses are well positioned to address these dimensions through active listening during telephone contacts, validated quality-of-life screening, and timely referral to psychological support services when needed.
Conclusion
IEC-colitis after CAR T-cell therapy highlights the need for sustained multidisciplinary vigilance well beyond the acute post-infusion period. A proactive nursing follow-up model, combining a dedicated helpline with systematic weekly telephone contact for remote patients, enabled early symptom detection and rapid clinical evaluation in this case. Nurses, as continuous patient advocates, are essential in bridging the gap between symptom onset and diagnosis, and in supporting patients through a treatment trajectory that extends far beyond hospital discharge.
Future Clinical Case of the Month
If you have a suggestion for future clinical case to feature, please contact Anna Sureda.