Summary

• CARTITUDE-1 (MMY2001) was a phase 1b/2, open-label study evaluating CARVYKTI in patients with relapse or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI), immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).^1-4
  • Berdeja et al (2021)^1,3 published primary results of CARTITUDE-1 at a median follow-up of 12.4 months. Bridging therapy was allowed when clinically indicated (i.e. to maintain disease stability while waiting for manufacturing of CARVYKTI). Overall, 75% of patients (n=73) received bridging therapies between apheresis and CARVYKTI infusion.
  • Based on CARTITUDE-1 data, enhanced bridging therapy was implemented across the CARVYKTI development program to help prevent or reduce the incidence and severity of neurological adverse events (AEs), including parkinsonism. Enhanced bridging is defined as an investigator-directed approach to lowering baseline tumor burden prior to chimeric antigen receptor (CAR)-T cell infusion.^1,5

• CARTITUDE-4 (MMY3002) is a phase 3, open-label study evaluating CARVYKTI versus standard care regimens (pomalidomide, bortezomib, and dexamethasone [PVd] or DARZALEX FASPRO [daratumumab and hyaluronidase], pomalidomide, and dexamethasone [DPd]) in patients with relapsed and lenalidomide-refractory multiple myeloma (MM) who received 1-3 prior LOTs, including a PI and an immunomodulatory drug.⁶
  • San-Miguel et al (2023)⁶ published primary results of CARTITUDE-4 at a median follow-up of 15.9 months. Patients in the CARVYKTI arm received at least 1 cycle of bridging therapy with PVd or DPd (with the number of cycles based on clinical status and manufacturing time).
  • Anguile et al (2024)⁷ presented a post hoc analysis evaluating the efficacy of CARVYKTI based on patient’s response to bridging therapy, with a median follow-up of 15.9 months.
• Dhakal et al (2025)⁸ reported a multicenter retrospective study that evaluated safety and efficacy of a short course of TALVEY (0.8 mg/kg, subcutaneously every other week) as a bridging therapy prior to CARVYKTI or idecabtagene vicleucel (ide-cel) infusion in patients with RRMM. At a median follow-up of 6.9 months (interquartile range [IQR], 5.2-10.3), the median progression-free survival (PFS) and overall survival (OS) were not reached. Following TALVEY bridging, the complete response (CR) rate with CARVYKTI vs ide-cel was 55% vs 47%. Following CAR-T treatment, any grade cytokine release syndrome (CRS) was reported in 68% of patients. Two patients experienced grade 3/4 CRS with CARVYKTI. Immune cell-associated neurotoxicity syndrome (ICANS) was reported in 7 patients with one grade 3 ICANS with CARVYKTI. There were no cases of parkinsonism, peripheral neuropathy or Guillain-Barré syndrome.
• Ailawadhi et al (2025)⁹ presented a retrospective cohort study of patients with RRMM who received CARVYKTI after more than 4 prior LOT to assess the association between bridging therapy with treatment-free interval (TFI) and OS. The median follow-up was 6.8 months. Bridging therapy vs non-bridging therapy patients had similar TFI rates (6 months; 95.0% vs 92.5% and 12 months; 87.8% vs 88.6%). OS rates for bridging therapy vs non-bridging therapy patients were comparable (6 months; 97.5% vs 95.4% and 12 months; 91.1% vs 91.6%). After adjusting for differences in baseline characteristics, patients with bridging therapy were less likely to have a TFI or OS event compared to patients without bridging therapy (adjusted HR for TFI, 0.68; 95% CI, 0.24-1.95; adjusted HR for OS, 0.65; 95% CI, 0.14-3.02).
• Sidana et al (2025)¹⁰  reported a retrospective study that evaluated outcomes with CARVYKTI after exposure to ≥4 prior LOTs. Bridging therapy administered in 78% of patients had overall response rate (ORR) of 27%. Response to bridging therapy did not affect the PFS, and the response rates.

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.
• TALVEY (talquetamab) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc. https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-pi.pdf

clinical data - cartitude-1 - PHASE 1B/2 STUDY

CARTITUDE-1 (MMY2001; NCT03548207) was a phase 1b/2, open-label, multicenter study that evaluated the safety and efficacy of CARVYKTI in patients with RRMM.^1-4

Study Design/Methods

• Bridging therapy refers to as a short-term anti-plasma cell directed treatment administered between apheresis and the start of the conditioning/lymphodepletion regimen.³
  • Bridging therapy had to involve agents previously used by the patient that had resulted in at least stable disease.¹
  • Additional cycles of bridging therapy could be considered based on patient’s clinical status and timing of availability of CARVYKTI.³
  • Patients were not permitted to receive CARVYKTI infusion if they had CR after bridging therapy.³
• Based on CARTITUDE-1 data, patient management strategies were implemented across the CARVYKTI development program to prevent or reduce the incidence and severity of neurological AEs/parkinsonism.^1,2,6
• In CARTITUDE-1, patients who experienced movement and neurocognitive treatment-emergent adverse events (MNTs) were typically characterized by the presence of at least two of the following factors: high tumor burden, grade ≥2 CRS, any grade ICANS following CARVYKTI infusion, and high CAR T-cell expansion or persistence.^1,2,5
• To mitigate the risk of MNTs, several strategies were implemented across the CARVYKTI development program, including enhanced bridging therapy and extended neurotoxicity monitoring.⁵
• Enhanced bridging therapy provided investigators with greater flexibility in both the selection and duration of treatment, including the option to use agents the patient had not previously received, to effectively reduce baseline tumor burden prior to CARVYKTI infusion.⁵
  • Enhanced bridging therapy was not implemented in CARTITUDE-1. It was implemented in CARTITUDE-2 and subsequent studies in the CARTITUDE program.

Results

Treatment Disposition and Treatment Characteristics

• Overall, 75% of patients received bridging therapies (systemic corticosteroids, antineoplastic agents, or immunosuppressants) between apheresis and CARVYKTI infusion. See Table: CARTITUDE-1: Bridging Therapies for a complete listing of therapies.¹
• During the bridging therapy period prior to lymphodepleting chemotherapy, 52% of patients (n=38) showed either an increase or no change in M-protein and/or serum free light chains (sFLCs), while 45% (n=33) demonstrated a decrease. No patients achieved a CR, and 3% (n=2) were not evaluable at baseline.^1,3

CLINICAL DATA - CARTITUDE-4 - PHASE 3 STUDY

CARTITUDE-4 (MMY3002; NCT04181827) is a phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (PVd or DPd) in patients with lenalidomide-refractory MM after 1-3 prior LOTs.⁶

San-Miguel et al (2023)⁶ published primary results of CARTITUDE-4 at a median follow-up of 15.9 months (range, 0.1 - 27.3). Patients in the CARVYKTI arm received at least 1 cycle of bridging therapy with PVd or DPd (with the number of cycles based on clinical status and manufacturing time).

Study Design/Methods.

• Patients were randomized 1:1 to receive either CARVYKTI or standard care (PVd or DPd).⁶
• CARVYKTI arm: After undergoing apheresis, patients arm received ≥1 cycle of bridging therapy with PVd or DPd (number of cycles was based on clinical status and CARVYKTI manufacturing time).⁶
  • PVd as bridging therapy was administered as 21-day cycles of pomalidomide 4 mg orally (PO) daily for 14 days; bortezomib 1.3 mg/m² subcutaneously (SC) on bridging days 1, 4, 8 and 11 and dexamethasone 20 mg PO on bridging days 1, 2, 4, 5, 8, 9, 11, and 12.^6,11
  • DPd as bridging therapy was administered as 28-day cycles of DARZALEX FASPRO 1800 mg SC weekly on days 1, 8, 15, and 22; pomalidomide 4 mg PO for 21 days and dexamethasone 40 mg PO or IV on bridging days 1, 8, 15, and 22 or split over 2 days (two-20 mg doses).^6,11
  • Physicians’ choice of PVd or DPd was based on the patient’s prior anti-myeloma therapy.¹²
  • Prior to initiating the lymphodepletion regimen, patients had to have a washout period which occurred from the last dose of bridging therapy. Cycles beyond bridging cycle 1 could be truncated to allow for adequate washout and minimize time off therapy.¹²
  • Patients who had confirmed disease progression during bridging therapy or lymphodepletion were assessed as having a progression event. Subsequent therapy with CARVYKTI could be administered at investigator discretion.⁶

Results

Treatment Disposition and Treatment Characteristics

• Overall, 419 patients were randomized to receive CARVYKTI (n=208) or standard care (n=211; DPd [n=183] or PVd [n=28]).⁶
  • All 208 patients randomized to the CARVYKTI arm received bridging therapy with either DPd (n=182) or PVd (n=26).
  • A total of 176 patients (84.6%) received CARVYKTI as study treatment (as-treated population). In the as-treated population, 21.6% of patients received 1 bridging therapy cycle, 58.5% of patients received 2 bridging therapy cycles, and 19.9% of patients received 3-6 bridging therapy cycles.^6,13

Anguile et al (2024)⁷ presented a post hoc analysis evaluating the efficacy of CARVYKTI in CARTITUDE-4 based on patient’s response to bridging therapy, with a median follow-up of 15.9 months (range, 0.1-27.3).

Study Design/Methods

• Patients in the CARVYKTI arm underwent apheresis and bridging therapy followed by a single CARVYKTI infusion 5-7 days after the start of lymphodepletion.⁷
  • Bridging therapy was physician's choice of either DPd or PVd.
• PFS was measured from randomization and evaluated from baseline to the start of lymphodepletion in patients with ≥25% tumor burden reduction vs <25% (defined as <25% decrease, no change, or an increase in tumor burden). Overall, 2 patients were not evaluable.⁷
• Tumor burden change was measured by determining the difference between paraprotein at baseline and at lymphodepletion for each patient.⁷
• The in vivo effector-to-target (E:T) ratio was derived from peak chimeric antigen CAR-T cell expansion, which was assessed by flow cytometry and normalized to pre-infusion serum soluble B-cell maturation antigen (sBCMA) levels.⁷

Results

Treatment Disposition and Treatment Characteristics

• A total of 176 patients received CARVYKTI as study treatment and all patients received bridging therapy with either DPd (n=158) or PVd (n=18).⁷
• During the period of bridging therapy, 148 patients (84%) had ≥25% tumor burden reduction, and 28 patients (16%) had <25% decrease.⁷
• Patient baseline details are presented in Table: CARTITUDE-4 Post Hoc Analysis: Baseline Disease Characteristics Based on Tumor Burden Decrease (CARVYKTI Arm).⁷

Efficacy by Response to Bridging Therapy

• The median PFS was not reached (95% CI, NE-NE) in patients with ≥25% tumor burden reduction vs. 19.2 months (95% CI, 15.8-NE) in patients with <25% decrease in tumor burden (HR, 0.32; 95% CI, 0.16-0.66). See Figure: PFS by Tumor Burden Change of ≥25% Between Baseline and Start of Lymphodepletion.⁷
  • The estimated 15-month PFS rates were 87.5% (95% CI, 80.6-92.1) and 74.0% (95% CI, 52.9-86.7) in patients with ≥25% and <25% tumor burden reduction, respectively.⁷

Biomarker Correlates of Response to Bridging Therapy and Post CARVYKTI Outcomes

• Among patients with biomarker data, patients with ≥25% decrease in tumor burden showed a comparable CAR-T peak expansion in the blood (C_max), lower sBCMA levels pre-infusion, and a higher in vivo E:T ratio vs patients with <25% decrease in tumor burden.⁷ See Figure: Cmax (A), sBCMA (B), and E:T Ratio (C) by Response to Bridging Therapy in Patients with ≥25% Tumor Reduction.⁷
  • The median (IQR) C_max was 479.5 (811.8) cells/mL vs 508 (1353.8) cells/mL in patients with ≥25% and <25% tumor burden reduction, respectively.⁷
  • The median (IQR) pre-infusion sBCMA was 6.2 (14.6) mg/mL vs 64.0 (216.5) mg/mL in patients with ≥25% and <25% tumor burden reduction, respectively.⁷
  • The median (IQR) normalized C_max was 62.6 (139.2) cells/mL vs 5.4 (62.3) cells/mL in patients with ≥25% and <25% tumor burden reduction, respectively.⁷
  • Lower pre-infusion sBCMA levels were observed in patients with greater tumor burden reduction; no correlation with C_max was noted.⁷
  • Patients with effective bridging therapy had a higher E:T ratio (adjusted for baseline tumor burden variations).⁷
• Patients with higher E:T ratios showed improvement in PFS.⁷
  • C_max was similar in the subgroups of patients with both higher and lower tumor burden.⁷

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 23 September 2025.