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, 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 LOT, including a proteasome inhibitor and an immunomodulatory drug, and are refractory to lenalidomide.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 presented a post hoc analysis investigating the correlation between response to bridging therapy in patients who were infused with CARVYKTI as study treatment or as subsequent therapy and efficacy and safety outcomes after a median follow-up of 30.4 months.
• Hansen et al (2025)⁹ reported a single-center, retrospective cohort study that evaluated outcomes with CARVYKTI after bridging therapy and assessed their association with low pre-lymphodepletion plasma cell burden (pre-LD PCB). Among patients with measurable disease at bridging therapy (n=115), 54% had a decreased disease burden; higher disease reduction was achieved with TALVEY (80%) vs other bridging therapy regimens and with 1 to 3 LOTs (68%) vs 4 to 5 LOTs or ≥6 LOTs. Patients with a decreased disease burden during bridging therapy vs patients with increased disease burden/stable disease exhibited lower high-risk cytogenetics (16% vs 60%), a higher rate of <50% pre-LD PCB (77% vs 55%), and lower median peak absolute lymphocyte count after infusion (0.5×10³/μL vs 0.97×10³/μL). Of the 115 patients who had measurable disease during bridging therapy, 92% achieved a partial response or better (≥PR) and 69% achieved a complete response or better (≥CR) after CARVYKTI. Overall response rate (ORR) and rate of ≥CR to CARVYKTI were higher among those who responded to bridging therapy and had decreased disease burden vs those with stable disease or increased disease burden (ORR, 95% vs 89%; ≥CR rate, 73% vs 64%). ORR (94% vs 88%) and rate of ≥CR (70% vs 58%) to CARVYKTI were higher in patients who had <50% pre-LD PCB vs ≥50% pre-LD PCB. Median progression-free survival (PFS) was 30 months (95% CI, 16.4-NR) in patients with low pre-LD PCB and 14 months (95% CI, 9.4-NR) in those with high pre-LD PCB. Grade ≥3 immune cell-associated neurotoxicity syndrome (ICANS) occurred in 1.6% vs 11% of patients and grade ≥3 cytokine release syndrome (CRS) occurred in 1.6% vs 7.5% of patients with decreased disease burden vs stable disease or increased disease burden. Grade ICANS ≥3 occurred in 3.9% vs 12% of patients and grade ≥3 CRS occurred in 0% vs 12% of patients with low pre-LD PCB vs high pre-LD PCB.
• Dhakal et al (2025)¹⁰ 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 PFS and overall survival (OS) were not reached. Following TALVEY bridging, the CR rate with CARVYKTI vs ide-cel was 55% vs 47%. Following CAR-T treatment, any grade CRS was reported in 68% of patients. Two patients experienced grade 3/4 CRS with CARVYKTI. 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)¹¹ 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)¹² reported a retrospective study that evaluated outcomes with CARVYKTI after exposure to ≥4 prior LOTs. Bridging therapy administered in 78% of patients had 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 study evaluating the efficacy and safety of CARVYKTI in patients with RRMM after ≥3 prior LOT including a PI, an immunomodulatory drug, and an anti-CD38 mAb.^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 (MMY3001; NCT04181827) is a Phase 3, randomized, open-label study evaluating the efficacy and safety of CARVYKTI versus standard care (physician's choice of DPd or PVd) in adult patients with lenalidomide-refractory MM after 1-3 prior LOT.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.^6,13
  • 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).^6,13
  • Physicians’ choice of PVd or DPd was based on the patient’s prior anti-myeloma therapy.¹⁴
  • 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.¹⁴
  • 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.^6,15

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

• 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).

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.

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.
  • 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.
  • 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.
  • 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.
  • Lower pre-infusion sBCMA levels were observed in patients with greater tumor burden reduction; no correlation with C_max was noted.
  • Patients with effective bridging therapy had a higher E:T ratio (adjusted for baseline tumor burden variations).
• 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.

Dhakal et al (2025)⁸ presented a post hoc analysis investigating the correlation between response to bridging therapy and efficacy and safety outcomes after CARVYKTI infusion, with a median follow-up of 30.4 months.

Study Design/Methods

• Patients with CARVYKTI as study treatment or as subsequent treatment were included in the analysis.⁸
• PFS was measured post hoc from CARVYKTI infusion.⁸
  • As per the protocol, disease evaluation prior to CARVYKTI infusion was scheduled at apheresis, on day 1±7 of each bridging cycle, starting with cycle 2, and ≤7 days before initiating lymphodepletion.

Results

Patient Characteristics and Treatment Responses

• A total of 196 patients received CARVYKTI infusion; of these, 176 received CARVYKTI as the study treatment and 20 who progressed on bridging therapy received CARVYKTI as subsequent treatment.⁸
• Overall, 172 patients (87.8%) received DPd as bridging therapy:⁸
  • CARVYKTI as study treatment subgroup: 89.8% (158/176)  
  • CARVYKTI as subsequent therapy subgroup: 70.0% (14/20)
• The median number of bridging therapy cycles were 2 (range, 1-6) for DPd and 3 (range, 2-4) for PVd in the CARVYKTI as study treatment subgroup and 2 (range, 1-4) for DPd and 2 (range, 1-3) for PVd in the CARVYKTI as subsequent therapy subgroup.⁸
• Treatment responses to bridging therapy before lymphodepletion are presented in Table: Response to Bridging Therapy (Before Lymphodepletion).⁸
• Patients achieving deeper responses (≥PR) to bridging therapy experienced better PFS and OS following CARVYKTI treatment, as detailed in Table: PFS and OS with CARVYKTI by Response to Bridging Therapy.

Outcomes in Patients Who Received CARVYKTI as Subsequent Therapy

• Among the 20 patients who received CARVYKTI as subsequent therapy, 8 patients underwent salvage therapy after progression on bridging therapy before CARVYKTI, with a median of 3 prior LOTs (range, 2-5), and 9 patients had ≥4 LOTs, making them ineligible for CARTITUDE-4.⁸
• The median PFS after CARVYKTI infusion was 7.4 months for patients with progressive disease during bridging.⁸
• By data cutoff, 14 PFS events, including 12 OS events, had occurred after CARVYKTI infusion.⁸
  • At a median follow-up of 28.6 months (range, 25.4-35.7), 6 patients (30%) derived benefit from CARVYKTI and were progression free.

Safety by Response to Bridging Therapy

• Patients with deeper responses to bridging therapy had lower rates of most adverse events of interest before CARVYKTI infusion as presented in Table: AEs of Special Interest.⁸

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 11 December 2025.