SUMMARY  

• Janssen does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by the regulatory agencies.
• Dhakal et al (2025)^1,2 published multicenter, retrospective study evaluating the efficacy and safety of TALVEY bridging therapy (BT; N=134) prior to standard-of-care (SOC) B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR-T) therapy (ciltacabtagene autoleucel [cilta-cel] or idecabtagene vicleucel [ide-cel]) in patients with relapsed/refractory multiple myeloma (RRMM).
• Fandrei et al (2025)³ published a retrospective, single-center study evaluating 52 patients who received BT prior to undergoing BCMA CAR-T therapy for RRMM. Of these patients, 5 received TALVEY as BT. The therapy's responses, its impact on leukapheresis and CAR-T cell production, as well as T-cell expansion dynamics were detailed.
• Grajales-Cruz et al (2024)⁴ presented a single-center, retrospective analysis evaluating the efficacy and safety of TALVEY 0.8 mg/kg subcutaneous (SC) every other week (Q2W) in 54 patients. Of these patients, 15 received TALVEY as BT to CAR-T therapy.
• Waldschmidt et al (2024)⁵ presented a multicenter, retrospective analysis evaluating bispecific antibodies (BsAb) as a debulking or BT after T cell apheresis for RRMM patients undergoing BCMA CAR-T therapy.
• Shaikh et al (2024)⁶ presented a multicenter, retrospective study evaluating the efficacy and safety of TALVEY (N=13) after leukapheresis but before CAR-T therapy.

CLINICAL DATA

Dhakal et al (2025)^1,2 published a multicenter retrospective study evaluating the efficacy and safety of TALVEY BT (N=134) prior to SOC BCMA-targeted CAR-T therapy (ide-cel or cilta-cel) in patients with RRMM.

Study Design/Methods

• The study was conducted across 18 United States (US) academic medical centers and 2 German centers.
• Eligibility:
  • Patients with RRMM who underwent leukapheresis and received TALVEY BT before commercial cilta-cel or ide-cel were included.
  • Patients who received TALVEY prior to apheresis as holding therapy and then continued as BT were also included.
• Endpoints:
  • Primary outcomes of the study included assessment of the efficacy, safety, and feasibility of TALVEY BT in patients intended to receive cilta-cel or ide-cel.
    • Safety outcomes included cytokine release syndrome (CRS; any and grade ≥3), immune effector cell-associated neurotoxicity (ICANS; any and grade ≥3), TALVEY related unique toxicities, delayed neurotoxicity, infections, secondary primary malignancies, and severe cytopenia (grade ≥3).
    • Efficacy outcomes included response rates to TALVEY and CAR-T therapies, progression-free survival (PFS), overall survival (OS), and non-relapse mortality (NRM; death due to a non–myeloma-related cause; deaths attributed to myeloma were censored at the time of death).

Results

Patient Disposition and Characteristics

• Out of 134 patients included in the study, 119 patients (89%) subsequently received CAR-T therapy (cilta-cel, n=98 [82%]; ide-cel, n=21 [18%]). See Table: Baseline Characteristics.
• Most patients started TALVEY after apheresis except 19 patients (14%) who received TALVEY before T-cell collection due to rapid disease progression.
  • Of the 19 patients, 3 patients couldn’t proceed with CAR-T infusion: 2 due to manufacturing failure and 1 due to disease progression.

TALVEY Bridging

• A total of 82% of patients received TALVEY 0.8 mg/kg SC Q2W after step-up dosing. See Table: Baseline Characteristics for the baseline characteristics of the 134 patients included in the study.
• The median treatment duration with TALVEY was 23 days (range, 13-52), and median number of TALVEY doses administered at 0.8 mg/kg or equivalent was 2 (range, 1-30).
• The median time from the last dose of TALVEY to CAR-T infusion was 26 days (range, 20-34).
• A total of 15 patients couldn’t proceed with CAR-T infusion.
• A total of 19 patients received TALVEY as a holding and BT prior to apheresis. See Table: Baseline Characteristics of Patients With TALVEY as a Holding and Bridging Therapy for additional details.

Efficacy

• The median follow-up from the first TALVEY dose was 6.9 months (interquartile range [IQR], 5.2-10.3) and the median follow-up from CAR-T infusion was 4.2 months (IQR, 3.1-7.1).
• Summary of response to TALVEY and best response to CAR-T therapies is presented in Table: Overall Response to TALVEY and CAR-T Therapy.
• Median PFS and OS were not reached in the CAR-T group.
• The probability of progression at 6 months from the first dose of TALVEY was 12.6% (95% confidence interval [CI], 7.6-20.6).
• Multivariate analysis for PFS and OS in patients receiving TALVEY bridging prior to CAR-T therapy is presented in Table: Multivariate Analysis for PFS and OS in Patients Receiving TALVEY Bridging Therapy Prior to CAR-T Therapy.
• CAR-T therapy following TALVEY BT led to a deepened response in 42% of patients.

Efficacy in Subgroups

• The response rates were 78% with and 95% without prior BCMA exposure.
• Response to TALVEY across different subgroups is presented in the Table: TALVEY Response Rate Across Different Subgroups.

Safety

• The safety outcomes of patients after receiving TALVEY BT prior to CAR-T is presented in Table: Safety Outcomes of Patients After Receiving TALVEY as a Bridging Therapy to CAR-T.
  • TALVEY toxicity across different subgroups is presented in Table: Safety Outcomes of TALVEY Across Different Subgroups.
  • Complete resolution of TALVEY-related toxicities was observed in 60% of patients at the time of the last follow-up.
• The incidence of CAR-T-associated adverse events (AEs) remained consistent irrespective of whether the TALVEY washout period was ≥4 weeks or <4 weeks. See Table: AEs Post CAR-T by TALVEY Washout.
• No patients had immune effector cell associated hemophagocytic lymphohistiocytosis like syndrome after CAR-T infusion.
• One patient developed acute myeloid leukemia (AML) 5 months post CAR-T infusion (cilta-cel).

Cytokine Release Syndrome

• CRS occurred with CAR-T in 77% of patients who had not experienced CRS with TALVEY, compared to 67% of patients who had experienced CRS with TALVEY.
• In the patients receiving only TALVEY BT, median time to CRS onset was 1 day.

Neurotoxicity

• ICANS occurred with CAR-T in 5% of patients who did not experience ICANS with TALVEY, compared to 50% of patients who had experienced ICANS with TALVEY.
• No cases of parkinsonism, peripheral neuropathy or Guillain-Barré syndrome were observed with CAR-T therapy; VII cranial nerve palsy was reported in two patients post–CARVYKTI administration, and both cases resolved completely.

Mortality

• A total of 21 patients died during the study, of which 10 patients did not receive CAR-T infusion.
  • Seventeen patients died due to myeloma, 2 patients due to septic shock, 1 each due to AML and pneumonia.

Fandrei et al (2025)³ published a retrospective, single-center study evaluating 52 patients who received BT prior to undergoing BCMA CAR-T therapy for RRMM.

Study Design/Methods

• This study explored various BT regimens before BCMA CAR-T therapy and assessed impact on clinical outcomes, in vivo CAR-T cell expansion, T cell compartment differentiation, and in vitro cytotoxicity to elucidate their effects on CAR-T cell proliferation and functionality.³ 

Results

Treatment Disposition/Patient Characteristics

• A total of 52 patients received BT prior to BCMA-directed CAR-T therapy. Patient characteristics are provided in the Table: Baseline Characteristics.³ 
• Median follow-up of the entire population (N=52) after CAR-T therapy was 6 months (range, 5-10).³ 

• Additional baseline characteristics of patients who received BsAb BT³:
  • At a median follow-up of 6 months (range, 4-10), patients had received 6 (range, 5-13) median prior lines of therapy.
  • A median of 3 BsAb cycles (range, 1-6) were administered before CAR-T therapy.
  • A total of 70% of patients were classified as triple-class refractory multiple myeloma (TCRRMM) and 20% were penta-refractory multiple myeloma (PentaRRMM).
  • High-risk cytogenetic abnormalities were present in 90% of cases, defined as amplification (more than 4 copies) or gain of 1q, t(4;14), t(4;16), or del(17/17p).
  • Using the Myeloma CAR-T Relapse (MyCARe) model, 20% of BsAb patients were classified as high risk, 70% as intermediate risk and 10% as low risk.

Leukapheresis

• A total of 9 out of 10 (90%) patients received their first BsAb dose before leukapheresis and had a median of 3 doses (range, 1-5).³ 
• Out-of-specification (OOS) CAR-T cell products were observed in 4 out of 10 patients.³ 
  • The median time between the last BsAb infusion and leukapheresis did not differ between leukapheresis resulting in OOS products (n=6, 43 days [range, 8–140]) and those resulting in successful productions (n=7, 43 days [range, 16–198], Wilcoxon rank-sum test; P=0.84).

Efficacy

• The median follow-up after CAR-T therapy was 6 months (range, 5-10).³ 
• ORR for the entire population (N=52) was 56% with a complete response (CR) of 8%, very good partial response (VGPR) of 19%, and partial response (PR) of 29%.³ 
  • In the BsAb cohort (n=10), 2 patients achieved CR, and 8 patients achieved a VGPR.
• Median PFS of the entire population (N=52) by response is not reached (NR) in patients achieving CR, 10 months (95% CI; 10-NR) in VGPR/PR, and 6 months (95% CI; 2-NR) in stable disease (SD)/progressive disease (PD).³ 
  • In the BsAb cohort, the median PFS was NR.

Safety

• After CAR-T therapy in the entire population (N=52)³:
  • CRS of grade 1 or 2 occurred in 75% of patients, with 27% requiring tocilizumab administration. 
  • Neurotoxicity occurred in 4 patients with grade 1 ICANS in 7.7% of patients.
• After BT, all patients who received BsAb experienced grade 1 CRS without requiring tocilizumab.³ 

CAR-T Cell Expansion and Tumor Debulking

• Major T-cell subsets which included CD4+ central memory, CD4+ effector, CD4+ effector memory, CD4+ thymic emigrants, CD8+ central memory, CD8+ effector, CD8+ effector memory, CD8+ thymic emigrants, naive CD4+, and naive CD8+ were relatively low across all BT regimens, suggesting lymphodepletion was not affected by the type of BT.³ 
• There was no difference in the total CAR-T cell expansion between BsAb and other BT regimens.³   
• Early expansion of CD4+CAR+ cells and a delayed expansion of CD8+CAR+ cells occurred in BsAb-treated patients, leading to an elevated CD4+CAR+/CD8+CAR+ ratio on day 7 (median, 2.3 [0.01–3.1] vs. 0.3 [0.03–3.7] with other BT, P=0.03).³ 
• Median serum BCMA (sBCMA) on day 0 for patients who received TALVEY BT was 4 ng/mL (range, 1-61) compared to 59 ng/mL (range, 1-1540) for those receiving other BT.³ 

T cell Differentiation and Exhaustion

• There was no observed difference in PD-1+, TIGIT+, TIM3+, LAG-3+ or VISTA+CD4+CAR+ and CD8+CAR+ in patients who received BsAb BT compared to other BT regimens.³ 
• Patients treated with BsAb had a higher fraction of PD-1+CD8+ and PD-1+CD4+ non-transduced T-cells at leukapheresis.³ 
• There was no difference in proportions of PD-1+CD4+ or PD-1+CD8+ non-transduced T cells between the BT regimens after CAR-T cell therapy.³ 
• A single-cell transcriptomic analysis revealed higher exhaustion scores in most CD4+ and CD8+ effector and exhausted subtypes at the time of leukapheresis for the entire population. However by days 30 and 100 post-CAR-T cell therapy, no differences in exhaustion scores were observed across CD4+ and CD8+ subsets.³ 

Grajales-Cruz et al (2024)⁴ presented a retrospective analysis of 54 patients with RRMM who received TALVEY at Moffitt Cancer Center from September 2023 to July 1, 2024. Of these patients, 39 patients were treated with TALVEY until disease progression or intolerable AEs, while 15 patients received TALVEY as BT to CAR-T.

Study Design/Methods

• Patients received TALVEY 0.8 mg/kg SC Q2W after step-up dosing.⁴
• American Society for Transplantation and Cellular Therapy (ASTCT) criteria were used to grade CRS and ICANS, and International Myeloma Working Group (IMWG) criteria were used to grade responses.⁴

Results

Efficacy

• At a median follow-up of 5.04 months (range, 0.3-11.6), responses to TALVEY BT are presented in the Table: Response to TALVEY Bridging Therapy to CAR-T.⁴       

Safety

• CRS occurred in 11 of 15 patients (73.3%) who received TALVEY BT.⁴

Waldschmidt et al (2024)⁵ presented a multicenter, real-world, retrospective analysis across 9 different centers in Germany evaluating BsAb (N=39) as a debulking or BT for RRMM patients undergoing BCMA CAR-T therapy.

Results

Treatment Disposition/Patient Characteristics

• A total of 39 patients received BsAb therapy prior to CAR-T treatment, of which 2 patients (5.1%) experienced CAR-T manufacturing failure, and 1 patient was excluded due to immature follow-up (<4 weeks after CAR-T ).⁵
• Patient characteristics are shown in Table: Patient Characteristics.⁵ 

Efficacy

• The ORR was 62.5% in patients treated with idecabtagene vicleucel (n=16, 41.2% achieving ≥VGPR) and 85% in those treated with ciltacabtagene autoleucel (n=20, 70.0% achieving ≥VGPR).⁵
• At a median follow-up of 5.1 months after CAR-T therapy, PFS for the entire cohort was 9.6 months (range, 0.7-NR), with no significant difference between idecabtagene vicleucel and ciltacabtagene autoleucel (P=0.63).⁵
• Disease stabilization at the time of lymphodepletion, but not at apheresis, showed a trend toward a longer duration of response to CAR-T (P=0.091).⁵
• Patients were categorized based on prior BsAb exposure to evaluate the impact of median PFS (Table: Median PFS Based on Prior BsAb Exposure Prior to Apheresis).⁵
• At the last follow-up, 8 of 39 patients (20.5%) had died from disease progression, and 1  of 39 patients (2.5%) had died from infectious complications.⁵

Shaikh et al (2024)⁶ presented a multicenter, retrospective study evaluating the safety and efficacy of TALVEY BT before CAR-T therapy. Patients included in this analysis received TALVEY as of June 1 2024.

Study Design/Methods

• Patients receiving TALVEY monotherapy (N=13) after leukapheresis for idecabtagene vicleucel or ciltacabtagene autoleucel therapy but before CAR-T therapy were included.⁶
• The IMWG criteria was used to evaluate response to therapy.⁶
• AEs were graded based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.⁶

Results

Patient Characteristics

• Baseline characteristics for the 13 patients who received TALVEY BT to CAR-T therapy are highlighted in the Table: Baseline Characteristics.⁶ 

Efficacy

• Response rates are shown in the Table: Response to TALVEY Bridging Therapy.⁶   

Safety

• No patients had progressive disease or developed new end-organ damage during BT. At the final data cutoff (July 1, 2024), all patients were alive.⁶
• AEs reported in the 13 patients receiving TALVEY as BT is shown in the Table: Incidence of Hematological and Non-Hematological AEs for Patients Receiving TALVEY.⁶ 

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 05 September 2025.