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.
• Lin et al (2026)¹ presented a retrospective analysis of 6 patients with relapsed/refractory multiple myeloma (RRMM) enrolled in CARVYKTI clinical trials who developed immune effector cell-associated enterocolitis (IEC-EC) after CARVYKTI infusion. The median time to onset of IEC-EC was 67 days.
• Mikkilineni et al (2026)² presented a retrospective study of 27 patients with multiple myeloma (MM) who developed IEC-EC after CARVYKTI infusion. The median time to onset of diarrhea was 82 days.
• Fortuna et al (2024)³ 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.
• Lim et al (2026)⁴ published a retrospective study of 9 patients with RRMM who developed IEC-EC after CARVYKTI infusion. The median time to onset of diarrhea was 85 days.
• Hamilton et al (2026)⁵ presented a retrospective study of 8 patients who developed IEC-EC after CARVYKTI infusion. The median time to onset of diarrhea was 64 days.
• Hansen et al (2026)⁶ presented a retrospective cohort study of 5 patients with RRMM who developed enterocolitis (EC) after CARVYKTI infusion. The median time to onset of EC was 130 days.
• Susanibar-Adaniya et al (2026)⁷ presented a multicenter case series of 19 patients who developed IEC-EC after CARVYKTI infusion. The median onset of diarrhea was 81 days.
• Bar et al (2024)⁸ presented a multicenter case series of 12 patients with MM who developed colitis after CARVYKTI infusion. The median onset of diarrhea was 98 days.
• Rolak et al (2025)⁹ 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)¹⁰ reported a case of a 66-year-old male patient with MM who developed eosinophilic colitis after CARVYKTI infusion.
• Hamidu and Rosenvinge (2024)¹¹ reported a case of a 67-year-old woman who developed colitis after CARVYKTI infusion.
• Other relevant literature on CARVYKTI-associated IEC-EC in patients with MM has been identified in addition to the data summarized above.¹²

CLINICAL DATA - RETROSPECTIVE DATA - CARTITUDE STUDIES

Lin et al (2026)¹ presented a retrospective analysis of patients with RRMM enrolled in CARVYKTI clinical trials (CARTITUDE-1, CARTITUDE-2 [cohorts A, B, and C], CARTITUDE-4, and CARTIFAN-1) who developed IEC-EC following CARVYKTI infusion.

Methods

• Cases reported from August 28, 2018, to January 16, 2025, were included in the analysis and patients were considered to have IEC-EC if they experienced grade ≥3 diarrhea, defined by the presence of ≥2 of the following:
  • Serious or prolonged (≥3 weeks) diarrhea with no direct infectious etiology
  • Gastrointestinal (GI) samples with crypt dropout, apoptotic changes, villous blunting, and/or T-cell infiltration (if biopsied).

Results

Patient Demographics and Clinical Characteristics

• Baseline characteristics in patients with IEC-EC (n=6) included median age (62 years), male sex (5/6) with Eastern Cooperative Oncology Group performance status (ECOG PS) 1 in 3/6 patients, ≥3 prior LOTs in 4/6 patients, high-risk cytogenetics in 4/6 patients, and bone marrow plasma cells ≥60% in 1/6 patients.

Clinical Course and Management of Patients With IEC-EC

• A total of 483 patients with RRMM were treated in the CARVYKTI clinical trials, 6 (1.2%) of whom developed IEC-EC.
• All 6 patients achieved a complete response or better (≥CR) following CARVYKTI infusion.
• None of the patients experienced cranial nerve palsy (CNP) or immune effector cell-associated parkinsonism (IEC-PKS).
• The median time to onset of IEC-EC was 67 days (range, 12-214) after CARVYKTI infusion.
• Patients with IEC-EC were treated with steroids (3/6) and cyclosporine (1/6); intravenous immunoglobulin (IVIG) was administered to 4/6 patients.
• Two patients with IEC-EC achieved a partial response after 3 cycles of bridging therapy (case 3: pomalidomide, bortezomib, and dexamethasone; case 5: daratumumab, pomalidomide, and dexamethasone).
• Among the 6 cases of IEC-EC, 4 were resolved; 2 patients had persistent symptoms until death due to multiorgan failure and coronavirus disease 2019 (COVID-19).
• A detailed summary of the clinical course of patients with IEC-EC is provided in Table: IEC-EC Cases Among Patients in CARTITUDE Studies.

Chimeric Antigen Receptor-Positive T Cells in the Blood of Patients With IEC-EC

• Persistence of chimeric antigen receptor (CAR)-positive T cells in the peripheral blood was longer in patients with IEC-EC vs patients without GI symptoms (controls) and was comparable vs patients with other GI symptoms.
• Patients with IEC-EC exhibited a longer depletion of IgA and B cells, a lower level of B cells, and a higher level of inflammatory cytokines (eg, interleukin-6) at onset vs the GI symptom-free control group at a comparable timepoint.
• No increase in T-cell receptor clonality in the peripheral blood was observed in association with the onset of IEC-EC or GI symptoms.

Histopathology of GI Biopsies From Patients Experiencing IEC-EC

• Plasma cells were largely absent in biopsy specimens from the stomach, duodenum, and colon, and findings indicative of injury were observed in the colon (66% of specimens) and duodenum (40% of specimens); see Table: Aberrant Findings by Biopsy Site.
• The presence of chimeric antigen receptor T cell (CAR-T) in the duodenal lamina propria did not appear to be associated with epithelial damage.

CLINICAL DATA - RETROSPECTIVE STUDIES

Multicenter Analysis Evaluating IEC-EC After CARVYKTI Infusion

Mikkilineni et al (2026)² 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 MM regimens as bridging therapy (n=18), 25.9% received high-dose or multiagent chemotherapy (n=7), and 7.4% received no bridging therapy (n=2).

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 CD4+, CD8+, CD4-/CD8-negative, or mixed CD4+/CD8+ patterns, reflecting heterogeneity across cases.

Multicenter Consortium Data: IEC-EC After CARVYKTI or Ide-cel Infusion

Fortuna et al (2024)³ 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, EC, 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.
• Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) were graded per the American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria. Diarrhea, colitis, and EC were graded per Common Terminology Criteria for Adverse Events (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 CNPs, with neurotoxicity resolution before the onset of EC 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 intravenous (IV) ganciclovir, with CMV clearance in 1 patient 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 adverse events, 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 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 Clostridium 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.

Mayo Clinic Experience: IEC-EC After CARVYKTI Infusion

Lim et al (2026)⁴ published a retrospective study of patients with RRMM who developed IEC-EC following CARVYKTI infusion.

Methods

• Medical records of patients with RRMM who received CARVYKTI between February 1, 2022, and November 30, 2024, at 3 Mayo clinic sites (Rochester, Florida, and Arizona) were retrospectively evaluated.
• CRS and ICANS were assessed according to the consensus grading criteria established by the ASTCT.
• Other toxicities were assessed using the National Cancer Institute Common Toxicity Criteria for Adverse Events v5.0.

Results

IEC-EC Diagnosis and Evaluation

• In the no delayed toxicity (n=214) and IEC-EC (n=9) groups, the median age was 65 (range, 31-82) and 66 (range, 51-77) years, and 54% (n=116) and 33% (n=3) of patients were male, respectively. Most patients had ECOG PS 0-1 (92% and 100%), with a higher proportion of high-risk disease per International Myeloma Society (IMS)/ International Myeloma Working Group (IMWG) criteria in the IEC-EC group vs no delayed toxicity group (78% vs 37%).
• Of 229 patients who received CARVYKTI, 9 (3.9%) patients developed IEC-EC; see Table: Postinfusion Characteristics.
• All 9 patients with IEC-EC experienced diarrhea that did not resolve and persisted for >2 weeks.
• The median time to onset of IEC-EC was 85 days (range, 35-166) from CARVYKTI infusion.
• All patients experienced grade ≥3 non-bloody and severe diarrhea per CTCAE; other common presenting symptoms included nausea and vomiting (4/9) and abdominal pain/discomfort (3/9).
• The median time from diarrhea onset to the first hospitalization was 31 days (range, 14-154), and 6 patients (67%) had >10% weight loss at the initial hospitalization.
• Elevated C-reactive protein (CRP) was observed in 4/5 patients (80%), and elevated ferritin was observed in 6/6 patients (100%).
• Among those who underwent subsequent stool testing for malabsorption, 3 patients showed elevated 24-hour fecal fat, and 4 patients showed evidence of bile acid malabsorption.
• Within 1 month of diarrhea onset, coinfections were encountered in 5 (56%) patients (norovirus infection, n=2; sapovirus infection, n=1; CDI, n=1; and norovirus + CDI, n=1), and 4 patients received antimicrobial directed therapy (oral vancomycin for Clostridium difficile and nitazoxanide for viral diarrhea); diarrhea persisted in all 4 patients.

Endoscopy Findings

• The median time to first endoscopy from onset of diarrhea was 49 days (range, 16-308).
• Seven of 9 patients (78%) had abnormal duodenal findings on esophagogastroduodenoscopy, with duodenal nodularity being the most common feature (5/9).
• Among 8 patients with colonoscopy findings, abnormal results were reported in 4 (50%).
• Six of 9 patients with IEC-EC had biopsy samples available for central pathology review, and all samples (from the duodenum, terminal ileum, and colorectum) showed plasma cell depletion.
• Biopsy details are provided in Table: Summary of GI Tract Biopsy Findings.

Cohort Survival Outcomes

• At a median follow-up of 14.1 months (95% confidence interval [CI], 12.2-16.6), progression had occurred in 31 patients and death in 29 patients.
• The estimated 12-month progression-free survival (PFS) and overall survival (OS) rates were 77% (95% CI, 70-83) and 88% (95% CI, 82-92), respectively.
• PFS did not differ significantly in patients with vs without IEC-EC (12-month PFS, 89% vs 77%; P=0.89).
• Among patients without IEC-EC, 35 deaths were reported, with 14 due to disease progression, 3 due to immune effector cell (IEC)-related causes, and the remaining due to other causes.
• Among patients with IEC-EC, 3 deaths were reported, attributed to concurrent IEC-EC and therapy-related myelodysplastic syndrome (n=1), IEC-PKS (n=1), and progressive disease (n=1).
• Nonrelapse mortality was higher in the IEC-EC group at 22% (2/9; 95% CI, 3-60) compared with 8% (18/220; 95% CI, 5-13) in patients without IEC-EC (P=0.18).

IEC-EC-Associated Risk Factors

• Patients who developed IEC-EC vs those who did not, had a higher prevalence of high-risk disease (odds ratio [OR], 6.1; 95% CI, 1.2-30; P=0.03); at lymphodepletion, elevated CAR-HEMATOTOX scores were more frequent patients with IEC-EC, and the use of alkylator-based bridging therapy showed a trend toward an association with IEC-EC.
• After CARVYKTI infusion, no differences were observed in the rates of any-grade or high-grade CRS, ICANS, and immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS); patients with IEC-EC experienced a longer CRS duration and more frequent need for repeated tocilizumab dosing.

Impact of Peak Lymphocyte Expansion

• Following CARVYKTI infusion, ALC expansion began after day 8 and peaked at a median of 12 days (interquartile range [IQR], 11-13).
• The median time to peak ALC was comparable between the IEC-EC group (11 days; IQR, 10.5-13.5) and controls (12 days; IQR, 11-13).
• Patients with IEC-EC demonstrated a higher peak ALC level vs controls (8.13×10⁹/L vs 2.3×10⁹/L; P=0.017). These patients also exhibited greater cumulative ALC expansion over 28 days (area under the curve [AUC]) attributable to patients who developed delayed neurotoxicity. Patients with IEC-EC without prior delayed neurotoxicity showed similar ALC_peak and ALC_AUC values compared with the control group.

Management Strategies and Outcomes

• First-line (1L) management:
  • Patients received a combination of IVIG (100%), budesonide (89%), and systemic steroids (56%).
    • Of 9 patients with IEC-EC, 3 (33%) experienced transient (<1 month) reduction in the stool count per day and required additional systemic therapies.
    • Of 9 patients with IEC-EC, 6 (67%) were refractory to 1L treatment.
• Second-line (2L) management:
  • Overall, 5 patients received 2L biologic therapy; the median time from symptom onset to treatment initiation was 3 months (range, 0.2-11).
    • Vedolizumab was administered to 2 patients; both achieved a durable response (grade ≤1 diarrhea and not requiring total parenteral nutrition [TPN] for >1 month) within 5 and 6 months, respectively and one patient continues vedolizumab as maintenance therapy.
    • Infliximab was administered to 3 patients; one achieved a durable response after 16 months. Of the 2 infliximab-refractory patients, 1 received third-line cyclophosphamide and has not yet responded after 1 month. The other patient was diagnosed with a CD4+ T-cell lymphoproliferative disorder and was later sequentially treated with cyclosporin, ruxolitinib, and upadacitinib. The patient failed to respond and currently remains on TPN.
• Overall, 4 patients did not receive biologic therapy as 2L treatment.
  • One patient received 2L high-dose cyclophosphamide and failed to respond after 1 month.
  • Three patients did not receive 2L therapy and died without symptom resolution or improvement after 4 to 24 months from onset of diarrhea.
• See Table: IEC-EC Management and Outcomes for details.

MD Anderson Cancer Center Experience: IEC-EC After CARVYKTI Infusion

Hamilton et al (2026)⁵ presented a retrospective study of patients who developed IEC-EC after CARVYKTI infusion.

Methods

• Medical records of 145 patients who received CARVYKTI at MD Anderson Cancer Center between July 2022 and July 2025 were retrospectively evaluated, and 8 suspected cases of IEC-EC were identified.

Results

Clinical Characteristics, Incidence, and CAR Exposure

• Among patients with suspected IEC-EC (n=8), the median age at infusion was 64.5 years and 5/8 patients were male.
• The cumulative incidence of IEC-EC at 6 months was 5.7% when progression and death were treated as competing risks.
• Among 6 evaluable patients with IEC-EC, CAR exposure during days 0-30 was 3.3-fold higher compared with 57 evaluable patients without IEC-EC, and CAR persistence beyond day 50 was 133-fold higher compared with 10 evaluable patients without IEC-EC.
• The median time to onset of diarrhea was 64 days from CARVYKTI infusion.

Gastrointestinal Pathologic Evaluation

• The GI pathologic evaluation of patients with IEC-EC ranged from mild to severe lymphocytic infiltration.
• Infiltrates were predominantly observed in the duodenum and terminal ileum; anti-camelid staining of GI tissue from 5 patients showed CAR-positive infiltration in all cases with heterogeneous T-cell tropism.
• In 2 patients with available GI flow cytometry, BCMA CAR-positive cells were identified in the duodenum.
  • One showed exclusively clonal CD4+ CAR-positive cells, while the other exhibited a mixture of polytypic CD8+ CAR-positive and clonal CD4+ CAR-positive T-cells.

IEC-EC Treatment and Outcomes

• Of the 4 patients who received cyclophosphamide (1-2 g/m²), 3 experienced an improvement in diarrhea output.
• One patient treated with infliximab followed by ustekinumab had initial improvement with subsequent relapse.
• Clonal T-cell populations were identified in 7 patients by T-cell receptor amplification or flow cytometry.
• Among 4 patients who underwent clinical sequencing using a 162-gene panel, no somatic gene mutations were detected.
• IEC-EC accounted for 3 of the 12 non-relapse deaths in the cohort, and 1 patient experienced relapse during the follow-up period.

Real-world Analysis of Enterocolitis After CARVYKTI Infusion

Hansen et al (2026)⁶ presented a retrospective cohort study of patients with RRMM who developed EC after CARVYKTI infusion.

Methods

• Electronic medical records from Loopback Analytics for patients who received CARVYKTI between February 2017 and June 2025 were retrospectively evaluated.
• The index date was CARVYKTI infusion; the baseline period comprised the 12 months prior to infusion, and the follow-up period extended from the index date to the earliest of death or end of data availability.
• New-onset EC after infusion was defined as the presence of ≥2 diagnosis codes (International Classification of Diseases, Tenth Revision, Clinical Modification [ICD-10-CM]: K52.1, K52.89, K52.9) recorded on separate days within 30 days, confirmed in physician notes, and with no EC diagnoses during the baseline period.
  • This study focused on EC, as the criteria for the diagnosis of IEC-EC may not have been consistently adopted.
• Inclusion criteria (N=423): Adult patients receiving CARVYKTI after 1-3 prior LOT (04/05/2024 to 06/30/2025) or ≥4 prior LOT (02/28/2022 to 06/30/2025), consistent with the approved indication; ≥2 MM diagnoses on distinct dates, including ≥1 pre-infusion; ≥12 months of pre-infusion data availability; evidence of lymphodepleting chemotherapy.
• Exclusion criteria (N=78): Clinical trial participation during the CARVYKTI LOT; diagnosis of amyloidosis prior to infusion; evidence of prior CAR-T infusion.

Results

Study Population and Patient Characteristics

• Of 345 patients treated with CARVYKTI, 5 developed new-onset EC.
• In the overall population (n=345) vs new-onset EC (n=5) groups, the median age was 66 (range, 37-83) vs 65 (range, 51-68) years, 44.3% (n=153) vs 20.0% (n=1) of patients were female, 8.7% (n=24) vs 0.0% (n=0) of patients had ECOG status ≥2, and 55.9% (n=90/161) vs 75.0% (n=3/4) had high-risk cytogenetic abnormalities.

Clinical Characteristics, Management, and Outcomes of EC

• Median time to onset of EC after CARVYKTI infusion was 130 days (range, 38-238).
• Structured EMR data identified infectious etiologies of diarrhea occurring between infusion and EC onset in 40% of patients (n=2).
• Management and outcomes of EC are summarized in Tables: Clinical Characteristics and Management of EC and Outcomes and Response to CARVYKTI.
• At the end of follow-up, all patients remained alive and did not require further treatment.

CLINICAL DATA - CASE Series and Case REPORTS

Multicenter Case Series Evaluating IEC-EC After CARVYKTI Infusion

Susanibar-Adaniya et al (2026)⁷ presented a multicenter case series of 19 patients who developed IEC-EC after CARVYKTI infusion.

Methods

• Data were retrospectively obtained from 6 United States (US) academic centers.
• Patients who developed unexplained diarrhea following CAR-T therapy between April 2022 and December 2024 were included in the analysis (after exclusion of infectious causes).
• Diarrhea/colitis were graded according to CTCAE version 5.0, whereas CRS and ICANS were graded using ASTCT criteria.
• Response to CAR-T therapy, progression, and survival data were collected in accordance with IMWG.

Results

Patient Characteristics

• At baseline, patients had a median age of 68 years (range, 39-77); females accounted for 40% of patients, high-risk cytogenetics were reported in 26% of patients, and 79% of patients were triple-class refractory.

IEC-EC Characteristics in Patients

• IEC-EC characteristics are summarized in Table: IEC-EC Characteristics in Patients.

Endoscopic and Histopathological Findings

• Histopathological and tissue findings are summarized in Table: Histopathological and Tissue Findings in Patients With IEC-EC.

IEC-EC Treatment Approaches

• Systemic corticosteroids (IV or oral) were administered to 11 patients (58%); symptomatic improvement was observed in only 1 patient.
• Infliximab was administered to 4 steroid-refractory patients, among whom 2 (50%) demonstrated improvement to grade 1.
  • Ruxolitinib was administered to two patients who responded; 1 achieved improvement with ruxolitinib followed by photopheresis, whereas the other received ruxolitinib for 7 days without improvement.
• Budesonide was administered to 9 patients and octreotide to 2 patients.
• TPN was administered to 9 patients (47%), with clinical benefit observed in 7 patients.

IEC-EC Treatment Outcomes

• At the last follow-up, complete resolution occurred in 7 patients (37%) with a median of 101 days (range, 30-312).
• Five patients (26%) improved to grade 1 with a median time of 100 days (range, 30-147).
  • One patient died due to infection related to IEC-EC.
  • One patient developed recurrent grade 3 colitis at day 441, was subsequently diagnosed with secondary acute myeloid leukemia (AML), and died thereafter.
• Seven patients (37%) had persistent grade ≥2 symptoms.
  • Of these, 4 (57%) died from IEC-EC-related complications (perforation or infection).
• Sixteen patients (84%) required ≥1 hospitalization.
• Infectious complications were reported in 6 patients, with a total of 9 events, including gram-negative bacteremia, nocardia, asymptomatic CMV reactivation, and disseminated zoster.
• Overall mortality was 37%, with 5 patients dying from IEC-EC, 1 from progressive myeloma, and 1 from secondary AML.
• Among the survivors, progressive myeloma occurred in 3 patients at a median of 606 days (range, 394-765), while the other patients remain in remission.

Multicenter Case Series Evaluating Colitis After CARVYKTI Infusion

Bar et al (2024)⁸ 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 IMWG 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 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.

Case of IEC-EC After CARVYKTI Infusion

Rolak et al (2025)⁹ 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.

Case of Eosinophilic Colitis After CARVYKTI Infusion

Coleman and Wang (2025)¹⁰ 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 LOTs 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 EC. 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 EC. 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.

Case of Colitis After CARVYKTI Infusion

Hamidu and Rosenvinge (2024)¹¹ 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 16 June 2026.