CARVYKTI - Bridging Therapy

Summary

• 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).^1-5
  • 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 (ie 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.^1,6
• CARTITUDE-4 is a phase 3, open-label, multicenter study evaluating CARVYKTI vs 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.^7,8
  • San-Miguel et al (2023)⁷ 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).
  • Einsele et al (2026)⁸ published results from a second interim analysis of overall survival (OS) and from an updated analysis of progression-free survival (PFS) in the intention-to-treat population from CARTITUDE-4 at a median follow-up of 33.6 months.
  • Anguile et al (2024)⁹ 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)¹⁰ 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.
• Real‑world studies assessing the use of bridging therapy for disease control before CARVYKTI infusion are included in the Clinical Data - Real‑world Studies section.

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

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

CARTITUDE-1 (NCT03548207) was a phase 1b/2, open-label study evaluating the efficacy and safety of CARVYKTI in patients with RRMM after ≥3 prior LOTs 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 a complete response (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.^1,2,7
• 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 cytokine release syndrome (CRS), any grade immune cell-associated neurotoxicity syndrome (ICANS) following CARVYKTI infusion, and high CAR T-cell expansion or persistence.^1,2,6
• To mitigate the risk of MNTs, several strategies were implemented across the CARVYKTI development program, including enhanced bridging therapy and extended neurotoxicity monitoring.⁶
• 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 CR, and 3% (n=2) were not evaluable (NE) at baseline.^1,3

CLINICAL DATA - CARTITUDE-4 - PHASE 3 STUDY

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 multiple myeloma (MM) after 1 to 3 prior LOTs.^7,8

San-Miguel et al (2023)⁷ 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).

Einsele et al (2026)⁸ published results from a second interim analysis of OS and from an updated analysis of PFS in the intention-to-treat population from CARTITUDE-4 at a median follow-up of 33.6 months (interquartile range [IQR], 20.3-35.0).

Study Design/Methods

• Patients were randomized 1:1 to receive either CARVYKTI or standard care (PVd or DPd).^7,8
• 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).^7,8
  • 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.^7,11
  • 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 intravenous on bridging days 1, 8, 15, and 22 or split over 2 days (two 20 mg doses).^7,11
  • 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.^7,8

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]).^7,8
  • All 208 patients randomized to the CARVYKTI arm received bridging therapy with either DPd (n=182) or PVd (n=26).^7,8
  • A total of 176 patients (84.6%) received CARVYKTI as study treatment (as-treated population).^7,8
  • 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.¹³

Anguile et al (2024)⁹ 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.⁹
• The in vivo effector-to-target (E:T) ratio was derived from peak CAR T-cell expansion, which was assessed by flow cytometry and normalized to pre-infusion serum soluble B-cell maturation antigen (sBCMA) levels.⁹

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).⁹
• During the period of bridging therapy, 148 patients (84%) had ≥25% tumor burden reduction, and 28 patients (16%) had <25% decrease.⁹
• 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% confidence interval [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 (hazard ratio [HR], 0.32; 95% CI, 0.16-0.66). See Figure: PFS by Tumor Burden Change of ≥25% Between Baseline and Start of Lymphodepletion.⁹
  • 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-cell 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.⁹ 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.⁹
  • C_max was similar in the subgroups of patients with both higher and lower tumor burden.

Dhakal et al (2025)¹⁰ 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.¹⁰
• PFS was measured post hoc from CARVYKTI infusion.¹⁰
  • 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.¹⁰
• Overall, 172 patients (87.8%) received DPd as bridging therapy:¹⁰
  • 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.¹⁰
• Treatment responses to bridging therapy before lymphodepletion are presented in Table: Response to Bridging Therapy (Before Lymphodepletion).¹⁰
• Patients achieving deeper responses (partial response or better [≥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-4.¹⁰
• The median PFS after CARVYKTI infusion was 7.4 months for patients with progressive disease during bridging.¹⁰
• By data cutoff, 14 PFS events, including 12 OS events, had occurred after CARVYKTI infusion.¹⁰
  • 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 AEs of interest before CARVYKTI infusion as presented in Table: AEs of Special Interest.¹⁰

Clinical Data - Real-World Studies

Details pertaining to select real-world studies assessing the use of bridging therapy prior to the use of CARVYKTI are summarized in Table: Results From Select Real-world Studies.

• Additional Real-world studies assessing the use of bridging therapy for disease control before CARVYKTI use are identified below.

Impact of Bridging Therapy Response on Neurotoxicity and Nonrelapse Mortality with CARVYKTI

Sidana et al (2025)¹⁴ reported a multicenter, retrospective study from the US Multiple Myeloma Immunotherapy Consortium evaluating outcomes of 761 patients treated with CARVYKTI with relapsed MM who were treated at 15 centers between May 2022 and December 2024.

• The median age was 65 years (range, 30-88), and patients had received a median of 5 prior LOTs (range, 1-23).
• A total of 86% patients received bridging therapy; response to bridging therapy (≥PR) was observed in 33% of patients.
• At a median follow-up of 10.1 months after CARVYKTI treatment, response rate was 92% and CR rate was 70%.
• Delayed neurotoxicity (DNT) occurred in 10% of patients (n=75) overall, including parkinsonism in 2.9% (n=22), cranial nerve palsy in 4.6% (n=35), and other DNTs in 2.4% (n=18); some patients experienced more than 1 type of DNTs.
  • The risk of DNT was higher in nonresponders to bridging therapy vs responders (any DNT, 12% vs 6%; Parkinsonism, 5% vs 0.5%; P<0.05 for both).
• Nonresponse to bridging therapy was identified as an independent risk factor for parkinsonism on multivariable analysis (odds ratio, 9.9; P=0.03).
• Among the 63 patients (8%) who experienced NRM events, the most common cause was infectious complications (56%; n=35), followed by acute immune‑mediated AEs (CRS, ICANS, or immune effector cell-associated hemophagocytic syndrome) in 22% (n=14), delayed immune‑mediated AEs (including DNT and colitis) in 9.5% (n=6), second malignancies in 8% (n=5), and other causes in 5% (n=3).
• On multivariable analysis, nonresponse to bridging therapy was independently associated with an increased risk of NRM (HR, 2.41; P=0.046).

Outcomes with TALVEY as Bridging Therapy Prior to CAR T-cell Therapy

Dhakal et al (2025)¹⁶ reported a multicenter retrospective study that evaluated safety and efficacy of a short course of TALVEY (0.8 mg/kg SC every other week) as a bridging therapy prior to CARVYKTI or idecabtagene vicleucel (ide-cel) infusion in 134 patients with RRMM.

• Among patients who received TALVEY, 119 patients proceeded to CAR T-cell therapy.
• At a median follow-up of 6.9 months (IQR, 5.2-10.3), the median PFS and OS were not reached.
• Skin-related AEs occurred in 38% of patients (primarily dry skin, pruritus, and exfoliation), oral AEs in 70% (mostly grade 1-2), nail AEs in 17% (all grade 1), and weight reduction in 15% (predominantly grade 1-2).
• Following TALVEY bridging, the CR rate with CARVYKTI vs ide-cel was 55% vs 47%.
• Response to TALVEY bridging did not differ significantly among patients with high-risk features, including extramedullary disease, high-risk cytogenetic abnormalities, prior BCMA-targeted therapy, and elevated baseline ferritin.
• CRS was reported in 68% (n=81; grade 1-2, n=79; grade 3, n=1; grade 4, n=1).
• ICANS was reported in 6% (n=7; grade 3, n=1).
• Infections were reported in 27 patients (16%; grade 3, 5%).
• Non-ICANS neurologic events were limited to two reversible cases of facial palsy, with no cases of peripheral neuropathy, Guillain-Barré syndrome, or parkinsonism.

Impact of Bridging Therapy Response on Efficacy, Safety, and Nonrelapse Mortality Following CAR T-cell Therapy

Rana et al (2025)¹⁷ reported, for a median follow-up of 12 months (IQR, 7-26), results from a single‑center, retrospective analysis of 135 patients with RRMM who received CAR T-cell therapy (CARVYKTI, n=85; ide‑cel, n=50) between May 2021 and March 2025.

• TALVEY was more frequently used with CARVYKTI vs ide-cel (20% vs 6%), whereas high‑dose alkylators were more commonly used with ide‑cel vs CARVYKTI (20% vs 16%).
• A ≥PR to bridging therapy was achieved in 41% of patients treated with CARVYKTI and 24% of patients treated with ide‑cel (P=0.04).
• The response rate was higher with TALVEY (92%) than with conventional therapy (23%) and high‑dose alkylators (85%) (P<0.001).
• Nonresponders vs responders to bridging therapy had a higher rate of ≥grade 2 CRS (31% vs 11%; P=0.05) and any DNT (26% vs 11%; P=0.1).
• Within 6 months of CARVYKTI infusion, death occurred in 15 patients.
• NRM was higher in patients who did not respond to bridging therapy vs responders (13% vs 6%).
• The CR rate was 60% with CARVYKTI and 42% with ide‑cel despite lower-grade bridging therapy responses. Among patients who did not respond to bridging therapy, 44% (12/27) treated with ide‑cel and 67% (26/39) treated with CARVYKTI achieved a CR following CAR T-cell therapy.

CARVYKTI Outcomes by Bridging Therapy Response and Pre-Lymphodepletion Disease Burden

Hansen et al (2025)¹⁸ 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).
• The 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 PFS was 30 months (95% CI, 16.4-not reached [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 ICANS 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.

Additional Real-world Studies

Additional real-world studies identified assessing the use of bridging therapy for disease control before CARVYKTI use include:

Impact of Bridging Therapy Use and Response on Progression-Free Survival with CARVYKTI

Sidana et al (2025)¹⁹ reported a multicenter retrospective study that evaluated outcomes with CARVYKTI after exposure to ≥4 prior LOTs in 255 patients with RRMM who underwent leukapheresis for CARVYKTI manufacturing between March 1, 2022 and December 31, 2022 at 16 United States academic medical centers.

• Bridging therapy administered in 78% of patients (n=184) had overall response rate (ORR) of 27%.
• In time‑to‑event analyses, patients who did not require bridging therapy demonstrated better PFS on univariate analysis (P=0.06) and response to bridging therapy did not impact PFS.
• CRS occurred in 75% (n=177; grade 1, n=115; grade 2, n=49; grade 3, n=6; grade 4, n=3; grade 5, n=3).
• ICANS occurred in 14% (n=32; grade 1, n=14; grade 2, n=8; grade 3, n=4; grade 4, n=4; grade 5, n=1).
• DNT occurred in 10% (n=24).
• Infection of any grade was reported in 47% (n=110); severe infections were reported in 46% (n=49).
• In the first 90 days, grade ≥3 neutropenia was reported in 80% (n=163), grade ≥3 anemia in 37% (n=61), and grade ≥3 thrombocytopenia in 53% (n=94).

Association of Bridging Therapy with Treatment-Free Interval and Overall Survival

Ailawadhi et al (2025)²⁰ published a retrospective cohort study of 242 patients with RRMM who received CARVYKTI after ≥4 prior LOTs to assess the association between bridging therapy with treatment-free interval (TFI) and OS at a median follow-up of 11 months. The data were accessed from Komodo Research Database (1/1/2016-06/30/2024).

• TFI rates at 6, 12, and 18 months were 94.0% (95% CI, 89.8-96.5), 89.0% (95% CI, 83.5-92.7), and 80.3% (95% CI, 70.9-87.0), respectively.
• OS rates at 6, 12, and 18 months were 97.3% (95% CI, 94.1-98.8), 93.4% (95% CI, 88.5-96.3), and 93.4% (95% CI, 88.5-96.3), respectively.
• 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, 0.76; 95% CI, 0.32-1.80; adjusted HR for OS, 0.48; 95% CI, 0.13-1.70).
• Patients who received bridging therapy with PI demonstrated a directional improvement in TFI (adjusted HR 0.36, 95% CI, 0.10-1.27) and OS (adjusted HR 0.30, 95% CI, 0.08-1.11) vs without BT; however, statistical significance was not achieved.

Outcomes with Bispecific T-cell Engagers Bridging Therapy Prior to CARVYKTI

Flores et al (2026)²¹ reported a single‑center, retrospective real‑world study from the Montefiore Medical Center evaluating the use of bispecific T‑cell engagers as bridging therapy prior to CARVYKTI infusion in 49 patients with RRMM from an underserved population, treated between September 2023 and March 2025.

• Among patients who received CARVYKTI, 17 received bispecific T‑cell engager therapy as bridging treatment (TALVEY in 12 patients, TECVAYLI in 3 patients, and other agents in 2 patients), with a median time from leukapheresis to CARVYKTI infusion of 63 days vs 64 days in patients who did not receive bridging therapy.
• CRS occurred in 59% of patients who received bispecific bridging therapy and in 81% of patients who did not receive bridging therapy (P=0.17).
• ICANS was not observed in patients who received bispecific bridging therapy but occurred in 4 patients who did not receive bridging therapy (P=0.29).
• The rate of prolonged cytopenias lasting for more than 30 days was similar in patients who received bispecific bridging therapy vs those who did not (52.9% vs 50%).
• The ORR after CARVYKTI was 91.9% (CR, 63.3%; very good partial response [VGPR], 20.4%; and partial response, 8.2%), with the CR rate comparable between patients who received bispecific bridging therapy vs those who did not (64.6% vs 62.2%; P=0.52).
• A total of 3 deaths occurred (2 with bispecific bridging therapy and 1 with no bridging therapy).
• At the last follow‑up, 88.2% of patients who received and 84.4% of those who did not receive bispecific bridging therapy remained progression free.

Clinical Outcomes and Safety of TALVEY Bridging Therapy Prior to CARVYKTI

Scott et al (2025)²² reported a single-center, retrospective real-world study from the Emory University Winship Cancer Institute evaluating TALVEY as bridging therapy prior to CARVYKTI infusion in 25 patients with RRMM treated between October 2023 and June 2025, with a median follow-up of 370 days from the start of bridging therapy.

• The median age was 66 years (range, 38-80), patients had received a median of 4 prior LOTs (range, 3-8), all were refractory to immunomodulatory agents, PIs and anti-CD38 monoclonal antibodies, and 24% (n=6) had received prior BCMA-directed therapy, including ide-cel in 3 patients.
• A total of 25 patients received TALVEY as bridging therapy; per institutional protocol, all patients received prophylactic tocilizumab prior to the first step-up dose.
  • Due to factors including rapid disease progression, 52% of patients (n=13) received a dose of TALVEY before leukapheresis.
  • The ORR of TALVEY bridging was 88% (n=22) with a ≥VGPR of 56%.
  • CRS occurred in 36% of patients (n=9; grade 1, n=7; grade 2, n=2).
  • ICANS occurred in 16% of patients (n=4; grade 4, n=1).
  • Among 24 patients evaluable for G protein-coupled receptor class C group 5 member D (GPRC5D)-associated toxicities, dysgeusia, ageusia, or xerostomia occurred in 100%, rash or non-rash skin changes in 67% (n=16), and nail changes or loss in 38% (n=9), all of which resolved by last follow-up.
  • Two deaths occurred prior to CARVYKTI infusion (hemophagocytic lymphohistiocytosis, n=1; disease progression on TALVEY, n=1).
• A total of 23 patients received CARVYKTI at a median of 87 days (range, 37-266) after TALVEY initiation.
  • By day 100 restaging after CARVYKTI infusion, all treated patients achieved ≥VGPR.
  • CRS occurred in 35% (n=8; grade 1, n=7; grade 2, n=1), and grade 1 ICANS occurred in 4.3% (n=1).
  • Disease progression was reported in 22% of patients (n=5) at a median of 209 days (range, 106-335) after CARVYKTI infusion.
    • Two deaths occurred after disease progression.

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 May 2026.