CARVYKTI - Adverse Event - Immune Effector Cell-Associated Enterocolitis (IEC-EC)

Summary

• Johnson & Johnson does not recommend the use of CARVYKTI in a manner that is inconsistent with the approved labeling.
• As clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• Mikkilineni et al (2026)¹ presented a retrospective study of 27 patients with multiple myeloma (MM) who developed immune effector cell-associated enterocolitis (IEC-EC) after CARVYKTI infusion. The median time to onset of diarrhea was 82 days.
• Lim et al (2025)² presented a retrospective study of 9 patients with relapsed/refractory multiple myeloma (RRMM) who developed IEC-EC after CARVYKTI infusion. The median time to onset of diarrhea was 3.5 months.
• Lim et al (2025)³ presented a retrospective study of 6 patients with MM who developed IEC-EC following CARVYKTI infusion. The median onset of diarrhea was 98.5 days.
• Fortuna et al (2024)⁴ conducted a retrospective analysis of 14 patients with MM who developed IEC-EC following CARVYKTI or idecabtagene vicleucel (ide-cel) infusion. The median onset of diarrhea was 92.5 days.
• Bar et al (2024)⁵ presented a multicenter case series of 12 patients with MM who developed colitis after CARVYKTI infusion. The median onset of diarrhea was 98 days.
• Blumenberg et al (2025)⁶ presented a case series of 5 patients with RRMM who developed IEC-EC after CARVYKTI infusion.
• Rolak et al (2025)⁷ reported a case of a 73-year-old woman with a history of immunoglobulin G (IgG) kappa MM who developed IEC-EC after CARVYKTI infusion.
• Coleman and Wang (2025)⁸ reported a case of a 66-year-old male patient with MM who developed eosinophilic colitis after CARVYKTI infusion.
• Hamidu and Rosenvinge (2024)⁹ reported a case of a 67-year-old woman who developed colitis after CARVYKTI infusion.

CLINICAL DATA - RETROSPECTIVE STUDIES

Mikkilineni et al (2026)¹ presented a retrospective study of patients with MM who developed IEC-EC following CARVYKTI infusion.

Methods

• Cases (N=27) of unexplained diarrhea following CARVYKTI infusion were retrospectively identified across 7 participating institutions between 2019 and 2024.
• Clinical, imaging, and pathological characteristics for each case were documented at the respective sites and subsequently evaluated through a centralized review.
• Based on author consensus, the cases were categorized as follows:
  • Mild/moderate (n=2); resolved with corticosteroids alone and without grade 4 toxicities
  • Severe (n=25); required biologic immunosuppression and/or complicated by grade ≥4 toxicities

Results

Patient Demographics and Clinical Characteristics

• In the overall population (N=27), the median age was 67.0 years (range, 50.0-80.0) and 77.8% of patients were male (n=21). The majority of patients (92.6%) received bridging therapy; 66.7% received standard multiple myeloma regimens as bridging therapy (n=18), 25.9% received high‑dose or multi‑agent chemotherapy (n=7), and 7.4% received no bridging therapy (n=2).
• High‑risk cytogenetic features were present in 37% of patients, and extramedullary disease was observed in 5% of patients.
• Grade 0-2 and grade 3 cytokine release syndrome (CRS) occurred in 96.3% and 3.7% of patients, respectively.
• Immune effector cell-associated neurotoxicity syndrome (ICANS) was uncommon and limited to low‑grade events, with grade 1-2 ICANS occurring in 11.1% of patients.

IEC-EC Characteristics in Patients

• The median time to onset of diarrhea was 82 days (n=23; range, 30-226) with a median absolute lymphocyte count (ALC) of 1.24 cells/µL at diarrhea onset (n=22; range, 0.08-0.310).
• Imaging studies in 26 patients showed colonic and small-bowel involvement in 70.4% and 40.7% of patients, respectively.
• Majority of the reported cases were classified as severe (70.3%).
• Mild cases were managed with supportive care, mesalamine, and/or corticosteroids, whereas severe cases were treated with infliximab, vedolizumab, cyclosporine, high‑dose cyclophosphamide, and/or ruxolitinib.
• Death related to IEC‑EC or associated complications occurred in 40.7% of patients (n=11).
• Detailed data are provided in Table: IEC-EC Complications and Treatment.

Endoscopic Evaluation and Histologic Profile

• Based on assessments conducted at individual centers, macroscopic endoscopic findings varied from normal mucosal appearance to visible endoscopic abnormalities.
• Histologic examination of duodenal biopsy samples showed villous blunting, a dense lamina propria with small to slightly enlarged lymphocytes exhibiting mild nuclear contour irregularities, and an increased number of intraepithelial lymphocytes.
• Focal apoptotic bodies were observed within the crypts.
• The cases included cluster of differentiation (CD) 4+, CD8+, CD4/CD8‑negative, or mixed CD4+/CD8+ patterns, reflecting heterogeneity across cases.

Lim et al (2025)² presented a retrospective study of patients with RRMM who developed IEC-EC following CARVYKTI infusion.

Results

IEC-EC Characteristics in Patients

• Of 235 patients who received CARVYKTI between February 2022 and December 2024 at 3 Mayo clinic sites, 9 (3.8%) patients developed IEC-EC.
• The median time to onset of IEC-EC was 3.5 months (range, 1.2-5.6) from CARVYKTI infusion.
• All patients experienced Common Terminology Criteria for Adverse Events (CTCAE) grade ≥3 non-bloody diarrhea; 3 (33%) had pneumatosis intestinalis, and 5 (56%) required total parenteral nutrition (TPN).
• At onset, co-infections were encountered by 5 (56%) patients (norovirus, n=2; sapovirus, n=1; Clostridium difficile, n=2) and 4 patients received anti-microbial directed therapy; diarrhea persisted for all patients after subsequent negative infection testing.
• Biopsy findings were as follows:
  • Abnormal duodenal biopsies were observed in 8/8 (100%) patients.
  • Abnormal colon biopsies were observed in 3/8 (38%) patients.
• Prior to IEC-EC, IEC-nerve palsies were observed in 2 patients and IEC-Parkinsonism (IEC-PKS) was observed in 3 patients.
  • Having delayed neurotoxicity was associated with IEC-EC (odds ratio [OR]=10.1; 95% confidence interval [CI], 2.5-41.2; P<0.01).

IEC-EC Predisposing Factors

• Use of alkylator-based bridging therapy, elevated CAR-HEMATOTOX scores, and delayed neurotoxicity may be associated with a higher risk of IEC-EC development. Selected potential associated risk factors are presented in Table: Characteristics Associated with IEC-EC.

Management Strategies and Outcomes

• First-line (1L) management:
  • Patients received combination of intravenous (IV) immunoglobulin (100%), budesonide (89%), bile acid sequestrants (78%), octreotide (33%) and systemic steroids (56%).
    • Of 9 patients, 3 (33%) patients had transient (<1 month) reduction in stool count per day and required additional systemic therapies.
    • Of 9 patients, 6 (67%) were refractory to 1L treatment.
• Second-line (2L) management:
  • Overall, 5 patients received 2L biologic therapy; median time from symptom onset to treatment initiation was 3 months (range, 0.2-11).
    • Vedolizumab (n=2) and infliximab (n=3) were administered; 3 patients (2/2 who received vedolizumab, 1/3 who received infliximab) achieved a durable response (≤ grade 1 diarrhea and not requiring TPN for >1 month) within 5-16 months.
      • One patient continues biologic therapy.
  • One biologic-refractory patient was diagnosed with an enteropathic T-cell lymphoproliferative disorder with DNA methyltransferase 3 alpha mutation and was treated with cyclosporin, ruxolitinib and upadacitinib sequentially and failed to respond.
  • One patient received 2L high dose cyclophosphamide and failed to respond after 1 month.
• Overall, 3 patients did not receive 2L treatment.
  • One patient remains alive with ongoing symptoms at 24 months.
  • Death occurred in 2 patients before symptom resolution (MM in 1 case, IEC-PKS in the other).

Lim et al (2025)³ presented a retrospective study of patients with MM who developed IECEC following CARVYKTI infusion.

Results

Patient Characteristics

• Out of 172 patients who received CARVYKTI between February 2022 and September 2024 at Mayo Clinic Minnesota, Arizona, and Florida, USA, 6 (3.5%) patients developed IEC-EC. The control group consisted of 82 patients who did not develop enterocolitis.
• At baseline, the median age was 61 years (range, 51-70) in the IEC‑EC group (n=6) and 63 years (range, 31-79) in the control group (n=82); females accounted for 67% and 51% of patients, and high‑risk cytogenetics were reported in 83% and 63% of patients, respectively.
• Bridging therapy was administered in 83% of patients in the IEC‑EC group and 66% of patients in control group; exposure to an alkylator within <3 months prior occurred in 67% and 23%, and CAR‑HEMATOTOX high‑risk status was observed in 67% and 21% of patients, respectively.
• The median onset of diarrheal symptoms was 98.5 days (range, 35-132) from CARVYKTI infusion.
• At the time of data cutoff, all cases were grade ≥3 based on CTCAE version 5.0.
• Increased odds of IEC-EC were observed in patients who received alkylator-based therapy within 3 months of CARVYKTI infusion (OR, 6.6; 95% CI, 1.1-3.90) and in patients who were CAR-HEMATOTOX high risk (OR, 7.4; 95% CI, 1.3-44.0).

Pre-lymphodepleting Chemotherapy and Month 1 After CARVYKTI Infusion

• Analyses of variables during pre-lymphodepleting chemotherapy and month 1 after CARVYKTI infusion in patients with IEC-EC vs the control group are presented in Table: Pre-lymphodepleting Chemotherapy and Month 1 After CARVYKTI Infusion.

Post-Chimeric Antigen Receptor T-cell (CAR-T) Therapy Toxicities

• Post-CAR-T toxicities in patients with IEC-EC vs the control group are presented in Table: Post-CAR-T Toxicities.

Fortuna et al (2024)⁴ conducted a retrospective analysis of 14 cases of IEC-EC following CARVYKTI or ide-cel infusion in patients with MM.

Methods

• A retrospective analysis was conducted on cases of diarrhea, enterocolitis, or colitis following commercial ide-cel or CARVYKTI infusions at 11 centers within the United States Multiple Myeloma Immunotherapy Consortium.
• Cases were identified through internal discussions at standing myeloma- and/or CAR-T-related meetings and, where available, through IEC compliance or long-term follow-up program databases.
• CRS and ICANS were graded per the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. Diarrhea, colitis, and enterocolitis were graded per CTCAE version 5.0.

Results

Patient Characteristics

• Out of the 14 cases of IEC-EC diagnosed at 1 of the 11 centers within the United States Multiple Myeloma Immunotherapy Consortium, 13 cases were due to post-CARVYKTI infusion, and 1 case was after ide-cel infusion.
  • The overall incidence of IEC-EC was 1.2% out of 1287 infusions (636 ide-cel and 651 CARVYKTI), with product-specific incidences of 0.2% for ide-cel and 2.2% for CARVYKTI. This calculation excluded 3 cases of patients with confirmed T-cell lymphoproliferative disorders.
• At baseline, patients had a median age of 64 years (range, 39-79); males accounted for 50% of patients (n=7), median prior lines of therapy were 4.5 (range, 4-7).
• Any‑grade CRS was reported in 93% of patients (n=13), CRS grade ≥2 in 29% (n=4), any‑grade ICANS in 7% (n=1), ICANS grade ≥2 in 7% (n=1).
• Following CARVYKTI infusion, 3 patients developed delayed cranial nerve palsies with neurotoxicity resolution before the onset of enterocolitis in 2 of these cases.

IEC-EC Characteristics in Patients

• IEC-EC characteristics at symptom onset in patients are presented in Table: IEC-EC Characteristics in Patients.
• All patients had grade ≥3 diarrhea; 10 (71%) also reported abdominal pain.
• Small or large bowel inflammation occurred in 6 (43%) cases, including 2 with diffuse colonic pneumatosis.
• Biopsies:
  • Colon biopsies showed ulceration, crypt dropout, and increased apoptosis.
  • Duodenal biopsies revealed villous blunting and marked intraepithelial lymphocytosis in 6 cases.
• Crypt architecture distortion was rare; features resembled graft-versus-host disease but all patients received autologous CAR-T therapy (no prior allogeneic transplant).
• Multiplex immunofluorescence/immunohistochemistry was used to detect CAR-transduced T cells (CD8+ and CD8-) infiltrating the duodenal lamina propria.
• At symptom onset, alternative bacterial causes of diarrhea were not identified.
• Peripheral blood cytomegalovirus (CMV) infections were negative in 7 cases, below the lower level of detection in 2 cases, and positive in 2 cases (peak values of 186 and 12800 IU/mL, respectively).
  • Both patients with CMV viremia received IV ganciclovir, with CMV clearance in 1 case and ongoing low-level positivity in the other.
  • Biopsy results for infectious agents were negative in all cases, including 2 patients with CMV viremia.

IEC-EC Treatment and Outcomes

• IEC-EC treatment and outcomes in patients are presented in Table: IEC-EC Treatment and Outcomes.
• Corticosteroids
  • Six patients received oral prednisone with a median starting dose of 0.87 mg/kg/day (range, 0.19-2) for a median duration of 21 days (range, 1-145).
  • Four patients received IV methylprednisolone with a median starting dose of 1.40 mg/kg/day (range, 1-2) for a median duration of 49 days (range, 20-68 days).
    • Median days of corticosteroid initiation were 26 days (range, 1-80) following symptom onset. Symptomatic improvements were noticed in 40% of steroid-treated patients.
• Infliximab
  • For immune-related AEs, 6 (43% of all cases) patients with corticosteroid-refractory symptoms were subsequently started with infliximab based on American Society of Clinical Oncology guidelines.
    • Median time to infliximab initiation was 61 days (range, 34-100) after diarrhea onset.
    • Symptomatic improvements were reported in half of the infliximab-treated patients after 1-3 doses.
• Vedolizumab
  • Vedolizumab was prescribed to 3 patients (21%) for overexpression of α4β7 integrin on CAR-T cells in the colon.
    • Median days of vedolizumab initiation were 59 days (range, 40-120) after diarrhea onset, with 1 of 3 patients having symptomatic improvement, but they subsequently developed Clostridioides difficile infection (CDI) and required fecal microbiota transplantation.

IEC-EC Status

• IEC-EC status at a median follow-up of 187 days (range, 44-532) since diarrhea onset is provided in Table: IEC-EC Status as of the Data Cutoff.
• Deaths were reported either due to directly from bowel perforation secondary to IEC-EC (n=3) or from treatment-emergent sepsis (n=2).
• Characteristics of patients with symptom resolution vs deceased patients are summarized in Table: Characteristics of Patients with Resolved Diarrhea vs Deceased Due to IEC-EC.

CLINICAL DATA – CASE Series and Case REPORTS

Bar et al (2024)⁵ presented a case series of 12 patients with MM who developed colitis after CARVYKTI infusion.

Methods

• Data were contributed by 5 academic centers and extracted using a retrospective chart review.
• Patients who developed unexplained diarrhea following CAR-T therapy were included in the analysis.
• Diarrhea was graded according to CTCAE version 5.0, whereas CRS and ICANS were graded using ASTCT criteria.
• Treatment response was evaluated based on the International Myeloma Working Group criteria.

Results

Patient Characteristics

• As of the data cutoff on May 20, 2024, a total of 12 patients were included in the study.
• At baseline, patients had a median age of 66 years (range, 39-77); females accounted for 50% of patients, high‑risk cytogenetics were reported in 25% of patients, and 83% of patients were triple‑class refractory.
• Key parameters of the post-CAR-T outcomes are presented in Table: Post-CAR-T Clinical Course.

Characteristics in Patients with Colitis

• Median time to onset of diarrhea after CARVYKTI infusion was 98 days (range, 60-211).
• At the time of data cutoff, 75% of patients were alive without disease progression.
• No lymphoproliferative disorder was reported at diagnosis or follow-up.
• Grade 3/4 diarrhea, cryptitis/apoptosis on biopsy, upper and lower gastrointestinal (GI) involvement, and pneumatosis intestinalis on imaging were reported in 92%, 83%, 83%, and 25% of patients, respectively.

Colitis Treatment and Outcomes

• Median time to resolution of colitis was 38 days (range, 30-56).
• Median time to grade 1 colitis was 124 days (range, 100-147).
• Out of 7 patients, 1 patient who received IV or high oral dose of steroids responded to treatment Treatments based on colitis response group are presented in Table: Treatments Based on Colitis Response Group.

Colitis-Related Events

• Events related to colitis are summarized in Table: Colitis-Related Events.

Blumenberg et al (2025)⁶ presented a case series of 5 (10.9%, n=46) patients with RRMM who received CARVYKTI treatment between January 2023 and February 2025, and developed IEC-EC; median onset occurred at 56 days (range, 40-151) post CARVYKTI infusion. Clinical features included at least CTCAE grade 3 non-bloody watery diarrhea, abdominal cramping, nausea, and emesis, with peak stool frequency of 11 times/day (range, 6-17) and a median maximum stool volume of 4200 mL/day (range, 3400-6700), leading to body weight loss (median 17.4 kg or 22.7% initial weight) and requirement for TPN in all patients (median duration, 57 days). Histological evaluation of GI biopsies showed active enteritis with CD3+ T cell infiltration and decreased or absent plasma cells in the lamina propria for all patients; Droplet Digital PCR confirmed CAR-T cells presence in GI tissue. Two patients achieved symptom resolution with supportive care and intermittent corticosteroids alone. Three patients who were non-responsive to vedolizumab and corticosteroids, were treated with ruxolitinib at a median of 140 days (range, 48-171) after onset, resulting in improvement within 1 to 7 days and leading to discontinuation of TPN within 5 to 44 days post-ruxolitinib. Complete symptom resolution occurred within 28-177 days post-ruxolitinib initiation; however, one patient had symptom recurrence after discontinuation, which was resolved upon re-initiation; two patients experienced disease progression while on ruxolitinib.

Rolak et al (2025)⁷ presented a case of a 73‑year‑old woman with a history of IgG kappa MM who was hospitalized with acute-onset, non-bloody diarrhea occurring 170 days after receiving CARVYKTI. The patient reported >4 L/day of non‑bloody stool accompanied by hypokalemia, hypernatremia, acute kidney injury with creatinine 2.83 mg/dL (from baseline 1.19 mg/dL), and albumin 3.4 g/dL. The patient tested negative for GI pathogen panel and Clostridium difficile. Colonoscopy appeared normal, and biopsies were negative for microscopic colitis or CMV; however, push enteroscopy revealed nodularity in the duodenum and jejunum. Jejunal biopsies showed villous blunting, crypt apoptosis, and increased intraepithelial lymphocytes with a predominance of CD4+ T cells. Genetic testing showed clonal T-cell receptor gene arrangements. The patient received IV methylprednisolone without significant improvement in her symptoms after 5 days, after which she was administered cyclophosphamide 1.5 mg/m². Given the occurrence of persistent diarrhea, 2 doses of 300 mg IV vedolizumab were administered 1 week apart, resulting in decreased diarrhea. At follow‑up, the patient was doing well with 2-3 bowel movements per day.

Coleman and Wang (2025)⁸ presented a case of a 66-year-old male patient with MM presenting with a complaint of watery stool 5-6 times per day (CTCAE grade 2). Despite several prior lines of treatment for MM, the patient had recurrent MM for which he received elotuzumab, pomalidomide, and dexamethasone for 2 years, followed by CARVYKTI, which helped achieve cancer remission. Two months after CARVYKTI infusion, the patient complained of several weeks of grade 2 diarrhea with weight loss and electrolyte abnormalities with a negative infectious workup, including a GI panel for 22 pathogens. The patient was started on cholestyramine, diphenoxylate/atropine, and budesonide without much response. Colonoscopy revealed eosinophils and apoptotic bodies in the ileum and throughout the colon, consistent with eosinophilic enterocolitis. C-reactive protein (CRP) was within normal limits (2.07). The patient had elevated CRP (12.62) when mesalamine was added with ongoing budesonide, and he had significant inflammation, grade 3 diarrhea, and weight loss. The patient was initiated on IV steroids alongside infliximab and a prednisone taper to manage refractory enterocolitis. His symptoms improved, with bowel movements decreasing to 3-5 semisolid episodes per day. After receiving the third infliximab dose and completing the prednisone taper, he reported complete resolution of both GI and systemic symptoms.

Hamidu and Rosenvinge (2024)⁹ reported a case of a 67-year-old woman with relapsed MM who was hospitalized with diarrhea 9 weeks after CARVYKTI infusion. Initial evaluation revealed mild colitis with positive stool test for CDI and negative for toxins A and B. Fidaxomicin was initially administered for presumed CDI but failed to resolve diarrhea, prompting colonoscopy on day 10 which revealed pseudomembranous exudate in the transverse colon, confirmed by biopsies. Retreatment with vancomycin failed to resolve diarrhea. The patient required supplemental parenteral nutrition. Systemic steroids were limited due to steroid myopathy. Hence, oral budesonide formulated for controlled ileal release was administered, which rapidly resolved diarrhea. Budesonide was successfully tapered 4 months after discharge, with no recurrence of diarrhea observed.

LITERATURE SEARCH

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) was conducted on 26 March 2026.