SUMMARY

• Renal impairment 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 (MMY2001) was a phase 1b/2, open-label, single-arm, multicenter study evaluating the efficacy and safety of CARVYKTI in patients with relapsed or refractory multiple myeloma (RRMM) who had received a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).^2-4
  • 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.⁵
• CARTITUDE-4 (MMY3002) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO^® [DPd]) in lenalidomide refractory multiple myeloma (MM) after 1-3 prior line(s) of therapy (LOT).^6,7
  • Re-testing was permitted prior to randomization.⁸
  • Per protocol, patient’s enrollment required adequate renal function during the screening phase defined as eGFR ≥40 mL/min/1.73 m² by MDRD.⁸
  • San-Miguel et al (2023)^6,9 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.
• Sidana et al (2025)¹⁰ evaluated the real-world outcomes of RRMM patients with renal impairment (RI) treated with CARVYKTI in a multicenter study.
• Pak et al (2024)¹¹ reported 2 cases of CARVYKTI use in patients with RRMM who were on maintenance hemodialysis (HD) for kidney failure at the Memorial Sloan Kettering Cancer Center, New York.

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 (MMY3002; NCT04181827) is an ongoing, phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician’s choice of PVd or DPd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.⁶

Study Design/Methods

• Re-testing was permitted prior to randomization.⁸
• Per protocol, patient’s enrollment required adequate renal function during the screening phase defined as eGFR ≥40 mL/min/1.73 m² by MDRD.⁸
• Patients were randomized to receive either CARVYKTI or standard care (PVd or DPd).⁸

Results

San-Miguel et al (2023)^6,9 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).⁶
  • The median PFS was not reached in the CARVYKTI arm and was 11.8 months (95% CI, 9.7-13.8) in the standard arm (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.⁹
    • 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).

real-world EXPERIENCE

Sidana et al (2025)¹⁰ 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 multi-center study, 21 (13%) patients who received CARVYKTI had RI; 8 of these 21 patients were on dialysis.¹⁰
• The median follow-up was 13 months.¹⁰
• Renal impairment 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).¹⁰

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.¹⁰
• 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.¹⁰
• Bridging therapy use and response were similar between the two groups.¹⁰
• Fludarabine/cyclophosphamide (Flu/Cy) was administered as lymphodepleting chemotherapy in 65% (n=13) vs 85% (n=174) of patients (P=0.08) with RI vs without RI.¹⁰
  • Among patients with renal impairment receiving Flu/Cy, fludarabine dose reduction was more common with renal impairment (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.¹⁰
  • When censoring non-myeloma related causes of death and focusing on progression alone, time to progression (TTP) was not significantly different by RI.

Safety

• AEs 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.¹⁰
• In patients with RI vs without RI, non-relapse mortality was 19% (n=4) vs 8% (n=16) (P=0.09) and was driven by CRS (n=2), immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome (IEC-HS; n=1), and infection (n=1).¹⁰
• In most patients, renal function did not significantly change after receiving CARVYKTI.¹⁰

Case reports

Pak et al (2024)¹¹ 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 case was a 50-year-old female patient who was initially diagnosed with κ-free light chain (FLC) International Staging System (ISS) stage III MM with high-risk cytogenetics (del[1p] and del[17p]). The patient presented with an acute kidney injury that required urgent HD. The patient received induction treatment with cyclophosphamide-bortezomib-dexamethasone and autologous hematopoietic stem cell transplantation for MM. Despite attaining a very good partial response (VGPR) and substantial decrease in serum FLC with treatment, the patient remained dependent on dialysis. The patient relapsed several times after initial treatment and received lenalidomide-bortezomib-dexamethasone, daratumumab-lenalidomide-dexamethasone, and carfilzomib-pomalidomide-dexamethasone. The patient achieved a VGPR after each regimen. The patient experienced disease progression 2.5 years after carfilzomib-pomalidomide-dexamethasone therapy, with a serum κ-FLC of 368 mg/L and κ/λ ratio of 20. A decision was made to administer CARVYKTI for relapsed MM.
  • Due to the underlying kidney failure, the patient received modified lymphodepletion and HD.
    • Lymphodepletion: cyclophosphamide 300 mg/m² (standard dose) and fludarabine 15 mg/m² (50% reduced dose)were administeredon days -5, -4, and -3.
    • During lymphodepletion, HD was performed 10.5-15 hours after each fludarabine dose using a high-flux dialyzer (Optiflux F160Nre) with blood flow rates of 300-350 mL/min. Each HD session lasted 6 hours. On day -3, the patient’s dialysis arteriovenous graft infiltrated during cannulation, necessitating urgent insertion of HD catheter.
  • CARVYKTI was administered on day 0 without issue. On day +1 (>24 hours post CARVYKTI infusion), the patient underwent a standard 4-hour HD session.
  • The patient did not experience CRS, ICANS, or fludarabine-related neurotoxicity after treatment.
  • The absolute neutrophil count reached a nadir on day +4 (0.7 x 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).
  • The platelet count remained above 100 x 10⁹/L.
  • The serum κ-FLC decreased from 141 mg/L to 0.8 mg/L and the κ/λ 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 case was a 70-year-old male patient with a history of κ-FLC ISS stage III MM with high-risk cytogenetics (del[17p]), polycythemia vera, hypertension, and MM-related kidney disease. The patient had received induction treatment with bortezomib-dexamethasone for MM and had achieved good hematologic response. The patient experienced disease progression and received treatment with carfilzomib-dexamethasone. Despite therapy, the patient developed kidney failure and was dependent on maintenance dialysis. Subsequently, the patient received treatment with carfilzomib-lenalidomide-dexamethasone followed by daratumumab-bortezomib-dexamethasone and was on maintenance treatment with daratumumab-bortezomib for the last 3 years before presenting with a serum M-spike of 0.74 g/dL, serum κ-FLC of 168 mg/L, and κ/λ ratio of 8.26. Bone marrow examination revealed 20%-25% plasma cells (97.6% of the cells were abnormal). A decision was made to administer CARVYKTI for cytoreduction of MM to achieve eligibility for kidney transplant.
  • Lymphodepletion was modified to include administration of cyclophosphamide 300 mg/m² (standard dose) on days -5, -4, and -3. Fludarabine was not included in the lymphodepletion regimen.
  • HD was performed on days -6, -3, and -1 using a high-flux dialyzer (Optiflux F160Nre) with blood flow rates of 400 mL/min. Each HD session lasted 4 hours. HD sessions on days -1 and +1 were performed at least 24 hours apart from CARVYKTI infusion.
  • CARVYKTI was administered on day 0.
  • 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 x 10⁹/L on day +9; however, the count normalized by day +17 without any intervention.
  • The lowest hemoglobin count was 8.8 g/dL on day +10.
  • The lowest platelet count was 95 x 10⁹/L on day +10.
  • The patient did not require transfusions.
  • Disease restaging on day +28 showed a decrease in serum M-spike, κ-FLC, and κ/λ 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 κ/λ ratio remained normal at 0.93 on day +90.

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 12 August 2025.