CARVYKTI - Use in Patients with Renal Impairment

SUMMARY

• Renal impairment (RI) studies of CARVYKTI were not conducted. In patients with mild (creatinine clearance [CrCL] 60 to <90 mL/min) or moderate (CrCL 30 to <60 mL/min) renal dysfunction, CARVYKTI exposure (maximum concentration and area under the curve in the first 28 days) was similar to that in patients with normal renal function (CrCL ≥90 mL/min).¹
• CARTITUDE-1 is a phase 1b/2, open label, multicenter study of CARVYKTI in patients with relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs) including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-cluster of differentiation (CD) 38 monoclonal antibody (mAb).^2-5
  • Per protocol, enrollment required adequate renal function during the screening phase defined as: estimated glomerular filtration (eGFR) ≥40 mL/min/1.73 m² based upon Modified Diet in Renal Disease (MDRD) formula calculation or 24-hour urine collection.⁶
• CARTITUDE-4 is a phase 3, open-label, multicenter study evaluating CARVYKTI versus standard care regimens, DARZALEX FASPRO (daratumumab and hyaluronidase), pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib, and dexamethasone (PVd), in patients with RRMM who received 1-3 prior LOTs, including a PI and an immunomodulatory drug, and are refractory to lenalidomide.^7-9
  • Re-testing was permitted prior to randomization.¹⁰
  • Per protocol, patient’s enrollment required adequate renal function during the screening phase defined as eGFR ≥40 mL/min/1.73 m² by MDRD.¹⁰
  • San-Miguel et al (2023)^7,11 published efficacy and safety results from CARTITUDE-4 at a median follow-up of 15.9 months, including subgroup analysis on progression-free survival (PFS) by baseline renal function.
  • Einsele et al (2026)⁹ published efficacy and safety results from CARTITUDE-4 at a median follow-up of 33.6 months, including findings from a subgroup analysis of PFS and overall survival (OS) by baseline renal function.
• Sidana et al (2025)¹² evaluated the real-world outcomes of RRMM patients with RI treated with CARVYKTI in a multicenter study.
• Swamy et al (2025)¹³ reported a case series of 5 dialysis‑dependent patients (4 on hemodialysis [HD] and 1 on peritoneal dialysis [PD]) with RRMM who were treated with CARVYKTI.
• Pak et al (2024)¹⁴ reported 2 cases of CARVYKTI use in patients with RRMM who were on maintenance HD for kidney failure at the Memorial Sloan Kettering Cancer Center, New York.
• Aaron et al (2025)¹⁵ reported a case of CARVYKTI use in a patient with relapsed, triple‑class refractory immunoglobulin (Ig)A lambda multiple myeloma (MM) and end‑stage renal disease requiring continuous PD.

PRODUCT LABELING

• CARVYKTI (ciltacabtagene autoleucel) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/CARVYKTI-pi.pdf.
• DARZALEX FASPRO (daratumumab and hyaluronidase-fihj) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/DARZALEX+Faspro-pi.pdf

CLINICAL DATA - cartitude-4

CARTITUDE-4 (NCT04181827) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI vs standard care (physician's choice of PVd or DPd) in adult patients with lenalidomide-refractory MM after 1 to 3 prior LOTs.^7-9

Study Design/Methods

• Re-testing was permitted prior to randomization.¹⁰
• Per protocol, patient’s enrollment required adequate renal function during the screening phase defined as eGFR ≥40 mL/min/1.73 m² by MDRD.¹⁰
• Patients were randomized to receive either CARVYKTI or standard care (PVd or DPd).¹⁰

Results

San-Miguel et al (2023)^7,11 published efficacy and safety results from CARTITUDE-4 at a median follow-up of 15.9 months (range, 0.1-27.3) of patients who received CARVYKTI (n=208) or standard care (n=211; DPd [n=183] or PVd [n=28]).

• Efficacy was evaluated in the intention-to-treat (ITT) population (all randomized patients; CARVYKTI, n=208; standard care, n=211).⁷
  • The median PFS was not reached in the CARVYKTI arm and was 11.8 months (95% confidence interval [CI], 9.7-13.8) in the standard care arm (hazard ratio [HR] 0.26; 95% CI, 0.18-0.38; P<0.001).
  • Subgroup analysis of PFS by baseline renal function (<60 mL/min/1.73 m² vs ≥60 mL/min/1.73 m² by MDRD) favored CARVYKTI with results consistent with the ITT population.¹¹
    • Baseline renal function <60 mL/min/1.73 m²: HR 0.29; 95% CI (0.13-0.68).
    • Baseline renal function ≥60 mL/min/1.73 m²: HR 0.28; 95% CI (0.14-0.59).

Einsele et al (2026)⁹ published the efficacy and safety results from CARTITUDE-4 at a median follow-up of 33.6 months (interquartile range, 20.3-35.0) for patients who received CARVYKTI.

• Efficacy was evaluated in the ITT population (all randomized patients; CARVYKTI, n=208; standard care, n=211).
  • The median PFS was not reached (95% CI, 34.5 months-not evaluable [NE]) in the CARVYKTI arm and was 11.8 months (95% CI, 9.7-14.0) in the standard care arm (HR 0.29; 95% CI, 0.22-0.39).
    • Subgroup analysis of PFS by baseline renal function (<60 mL/min/1.73 m² vs ≥60 mL/min/1.73 m² by MDRD) is presented in Table: Subgroup Analysis of PFS by Baseline Renal Function.
  • The median OS was not reached (95% CI, NE) in the CARVYKTI arm and was not reached (95% CI, 37.7 months-NE) in the standard care arm (HR 0.55; 95% CI, 0.39-0.79; P=0.0009).
    • Subgroup analysis of OS by baseline renal function (<60 mL/min/1.73 m² vs ≥60 mL/min/1.73 m² by MDRD) is presented in Table: Subgroup Analysis of OS by Baseline Renal Function.

real-world EXPERIENCE

Sidana et al (2025)¹² presented real-world outcomes in patients with RRMM with RI treated with standard-of-care CARVYKTI.

Study Design/Methods

• Of the 233 patients enrolled in the multicenter study, 21 (13%) patients who received CARVYKTI had RI; 8 of these 21 patients were on dialysis.¹²
• The median follow-up was 13 months.¹²
• RI was defined as having CrCL <40 mL/min or being on dialysis while receiving chimeric antigen receptor T-cell (CAR-T) therapy (trial exclusion criterion).¹²

Results

Patient Characteristics

• RI was observed in older patients with revised International Staging System (R-ISS) stage 3 diseases driven by higher β₂-microglobulin levels, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≥2, higher ferritin levels, and lower hemoglobin levels.¹²
• The proportion of patients with high-risk cytogenetics, extramedullary disease, prior therapy, and penta-refractory status were comparable between patients with and without RI; however, RI patients had a lower likelihood of prior auto-transplant.¹²
• Bridging therapy use and response were similar between the 2 groups.¹²
• Fludarabine (Flu)/cyclophosphamide (Cy) was administered as lymphodepleting chemotherapy in 65% (n=13) vs 85% (n=174) of patients (P=0.08) with RI vs without RI.¹²
  • Among patients with RI receiving Flu/Cy, Flu dose reduction was more common with RI (85% vs 19%; P<0.01).

Efficacy

• A lower response rate, inferior PFS, and lower OS was observed in patients with RI vs without RI. Efficacy outcomes in patients with RI vs without RI are presented in Table: Efficacy Outcomes.¹²
  • When censoring non-myeloma related causes of death and focusing on progression alone, time-to-progression (TTP) was not significantly different by RI.

Safety

• Adverse events reported in patients with and without RI are summarized in Table: Adverse Events in Patients With RI and Without RI.
• A comparable rate of severe cytopenias on day 30 and day 90 was observed in patients with RI vs without RI.¹²
• In patients with RI vs without RI, nonrelapse mortality was 19% (n=4) vs 8% (n=16) (P=0.09) and was driven by cytokine release syndrome (CRS; n=2), immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS; n=1), and infection (n=1).¹²
• In most patients, renal function did not significantly change after receiving CARVYKTI.¹²

Case SERIES AND Case reports

Swamy et al (2025)¹³ reported a case series of 5 dialysis‑dependent patients (HD, n=4; PD, n=1) with RRMM who were treated with CARVYKTI per dose‑adjusted lymphodepletion and tailored dialysis schedules at the University of Chicago.

Study Design/Methods

• This analysis included 5 patients with RRMM and RI who were treated with CARVYKTI at the University of Chicago.
• Prior to CARVYKTI infusion, patients underwent lymphodepletion with the following:
  • For the 4 patients undergoing HD: reduced Flu (15 or 20 mg/m²) + Cy (300 mg/m²) on days -5, -4, -3 in 3 patients and days -6, -5, -3 in 1 patient; dialysis timing was coordinated to be approximately 12 hours after each lymphodepletion dose
  • For the patient undergoing PD: bendamustine (70 mg/m²) on days -6 and -5 (dose reduced from 90 mg/m²) instead of Flu/Cy
• The detailed dialysis regimen for patients undergoing HD is presented in Table: HD Prescription of Patients Receiving CARVYKTI.
• On day 0, patients received a CARVYKTI infusion of 0.3 to 0.7×10⁶ chimeric antigen receptor-positive (CAR+) T cells/kg, with continued individualized renal support thereafter.
• Safety was monitored in all patients.

Patient 1

• Safety and postinfusion events:
  • The patient developed grade 2 CRS, grade 2 immune effector cell-associated neurotoxicity syndrome (ICANS) and grade 2 IEC-HS, all of which were resolved with tocilizumab, siltuximab, high‑dose corticosteroids, and anakinra.
  • The patient experienced prolonged cytopenias requiring transfusion support and underwent stem cell rescue.
  • The patient developed cranial nerve VII palsy on day +45 that lasted 1 week and resolved on its own.
• Clinical outcomes:
  • The patient progressed despite additional therapies (including talquetamab and elranatamab) and ultimately died on day +293 due to multiorgan failure.

Patient 2

• Safety and postinfusion events:
  • On day +6, the patient developed a neutropenic fever and was managed for grade 1 CRS; he received acetaminophen and a single dose of tocilizumab for persistent fever, followed by dexamethasone with a 4‑day taper.
  • During hospitalization, he had anemia and thrombocytopenia but did not require transfusion; he was discharged on day +14.
  • After discharge, he developed cranial nerve VII palsy on day +33 and was treated with a 5‑day course of dexamethasone with improvement.
• Clinical outcomes:
  • Bone marrow biopsy performed on day +60 showed no evidence of disease; he further exhibited measurable residual disease negativity by next‑generation sequencing at 10^-6 sensitivity, and suppressed serum light chains, consistent with a stringent CR.
  • He had persistent secondary hypogammaglobulinemia and received regular intravenous immunoglobulin (IVIG). Bone marrow biopsy on day +390 also demonstrated minimal residual disease negativity. His response remains excellent, and he continues with outpatient HD 3 times per week.

Patient 3

• Safety and postinfusion events:
  • On day -5, the patient developed a fever and hypotension; peritonitis was ruled out, and she was treated with cefdinir.
  • On day -4, she developed recurrent fever, which was treated with acetaminophen, and experienced rigors, hypotension, and wheezing during an IVIG infusion, which was discontinued due to concerns of an infusion reaction. She received small fluid boluses, 1 dose of dexamethasone, broader‑spectrum antibiotics, and nightly PD with minimal ultrafiltration; her symptoms improved by day -2.
  • After infusion, she developed a fever consistent with grade 1 CRS on day 0 and continued with nightly PD through day +5.
• Clinical outcomes:
  • The patient was discharged on day +12 and was off dialysis.
  • As an outpatient, she maintained renal function and had her PD catheter removed. Day +62 positron emission tomography/computed tomography and bone marrow biopsy showed no evidence of myeloma, consistent with a stringent CR.
  • At 4 months after CARVYKTI infusion, disease progression was identified, with multiple osseous and extramedullary lesions; she received salvage bendamustine with minimal response, followed by talquetamab without response, after which disease control was briefly achieved again with salvage bendamustine. After 2 cycles, she elected to discontinue treatment and enroll in hospice and died 9 months after CAR-T therapy (day +274), having remained off dialysis from day +12.

Patient 4

• Safety and postinfusion events:
  • During CAR-T infusion, the patient experienced transient left‑sided chest and arm pain; subsequent cardiac evaluation was unremarkable.
  • Her clinical course was unremarkable through day +9, and she was discharged; however, on day +10, she was admitted with headache, shortness of breath, and a neutropenic fever consistent with grade 1 CRS.
  • She was treated with acetaminophen and tocilizumab and received dexamethasone for 4 days because of concerns of grade 1 IEC-HS; she was discharged on day +14 after symptom resolution and improvement in inflammatory markers.
  • After discharge, she developed anemia, thrombocytopenia, and neutropenia, requiring 3 doses of filgrastim.
• Clinical outcomes:
  • On day +60, she achieved a partial response, with a reduction in monoclonal IgG lambda from 2.89 g/dL to 0.68 g/dL; bone marrow biopsy demonstrated no evidence of disease, with minimal residual disease negativity by next-generation sequencing at a sensitivity of 10^-6.She continues to receive outpatient HD 3 times per week.

Patient 5

• Safety and postinfusion events:
  • During CAR-T infusion, she experienced transient hypoxia on room air to 89% and required supplemental oxygen via a nasal cannula.
  • On day +4, she developed fever and neutropenia, and received acetaminophen, tocilizumab, and 1 dose of dexamethasone for grade 1 CRS.
  • She received 2 additional doses of tocilizumab over the subsequent 2 nights for recurrent fever and was started on scheduled dexamethasone, with dose escalation the following day due to another febrile episode.
  • On day +9, anakinra was initiated for IEC-HS.
  • On days +10, +11, and +12, she received cryoprecipitate for hypofibrinogenemia. She required 2 additional units of cryoprecipitate and 1 unit of packed red blood cells.
  • On day +13, the frequency of anakinra was increased, and ruxolitinib was added due to persistently rising ferritin levels; consequently, ferritin began to decline by day +15, and immunomodulatory therapy was tapered.
• Clinical outcomes:
  • At the time of discharge on day +26, the glomerular filtration rate estimated by creatinine and cystatin C was approximately 10 mL/min/1.73 m², and she was anticipated to require HD at least twice weekly.
  • By day +42, her kappa-free light chain (FLC) level had normalized, and although cytopenias persisted, she did not require blood product support or filgrastim.
  • By day +99, she developed evidence of extramedullary myeloma involvement and was receiving outpatient HD 3 times per week at that time.

Pak et al (2024)¹⁴ reported 2 cases of CARVYKTI use in patients with RRMM who were on maintenance HD for kidney failure at the Memorial Sloan Kettering Cancer Center, New York.

• The first patient was 50-year-old female who was initially diagnosed with kappa-FLC International Staging System (ISS) stage III MM with high-risk cytogenetics (del[1p] and del[17p]).
  • Safety and postinfusion events:
    • The patient did not experience CRS, ICANS, or Flu-related neurotoxicity after treatment.
    • The absolute neutrophil count reached a nadir on day +4 (0.7×10⁹/L) and normalized without intervention on day +10.
    • On day -1, the patient received 1 unit of packed red blood cells for a hemoglobin of 6.8 g/dL and remained transfusion-free while the patient’s hemoglobin returned to baseline on day +40 (9.4 g/dL) and platelet count remained above 100×10⁹/L.
  • Clinical outcomes:
    • The serum kappa-FLC decreased from 141 mg/L to 0.8 mg/L and the kappa/lambda ratio decreased from 19.29 to 0.42 after treatment. These values remained low on the latest patient follow-up on day +64.
    • No immunohistochemical or immunophenotypic evidence of disease was identified on bone marrow examination on day +28.
• The second patient was a 70-year-old male patient with a history of kappa-FLC ISS stage III MM with high-risk cytogenetics (del[17p]), polycythemia vera, hypertension, and MM-related kidney disease.
  • Safety and postinfusion events:
    • The patient experienced grade 1 CRS with fevers on days +6, +8, and +9. The fever subsided after treatment with tocilizumab on day +6 and dexamethasone on days +8 and +9.
    • The patient did not experience ICANS after treatment.
    • The absolute neutrophil count dropped below 0.5×10⁹/L on day +9; however, the count normalized by day +17 without any intervention.
    • On day +10, the lowest hemoglobin and platelet counts were 8.8 g/dL and 95×10⁹/L, respectively, and transfusions were not required.
  • Clinical outcomes:
    • Disease restaging on day +28 showed a decrease in serum M-spike, kappa-FLC, and kappa/lambda ratio.
    • No plasma cell neoplasm was identified on bone marrow biopsy (via immunohistochemistry and flow cytometry).
    • The serum M-spike further decreased to 0.18 g/dL and kappa/lambda ratio remained normal at 0.93 on day +90.

Aaron et al (2025)¹⁵ reported a case of CARVYKTI use in a 51-year-old male patient with relapsed, triple‑class refractory IgA lambda MM and end‑stage renal disease requiring continuous PD.

• Safety and postinfusion events:
  • The patient experienced grade 1 CRS on day +7 after CARVYKTI infusion; CRS was resolved with supportive care.
  • The patient experienced grade 3 anemia, grade 4 thrombocytopenia, and grade 3 neutropenia, with no neurotoxicity, delayed motor‑neurotoxicity, or clinically significant infections reported. These events occurred within 2 months after CARVYKTI infusion.
• Clinical outcomes:
  • Restaging bone marrow assessment revealed no evidence of disease, and the patient’s myeloma markers had decreased markedly, indicating an early treatment response.

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 15 April 2026.