SUMMARY  

• Janssen does not recommend any practices, procedures, or usage that deviate from the product labeling or are not approved by the regulatory agencies.
• Fandrei et al (2025)¹ published a retrospective, single-center study evaluating 52 patients who received bridging therapy (BT) prior to undergoing B-cell maturation antigen chimeric antigen receptor (BCMA CAR-T) therapy for relapsed/refractory multiple myeloma (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.
• Dhakal et al (2024)² presented a multicenter, retrospective study evaluating the safety and efficacy of TALVEY (N=77) as BT before BCMA-targeted CAR-T therapy.
• Grajales-Cruz et al (2024)³ 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)⁴ 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)⁵ presented a multicenter, retrospective study evaluating the safety and efficacy of TALVEY (N=13) after leukapheresis but before CAR-T therapy.

CLINICAL DATA

Fandrei et al (2025)¹ 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.¹ 

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.¹ 
• Median follow-up of the entire population (N=52) after CAR-T therapy was 6 months (range, 5-10).¹ 

• Additional baseline characteristics of patients who received BsAb BT¹:
  • 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).¹ 
• Out-of-specification (OOS) CAR-T cell products were observed in 4 out of 10 patients.¹ 
  • 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).¹ 
• Overall response rate (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%.¹ 
  • In the BsAb cohort (n=10), 2 patients achieved CR and 8 patients achieved a VGPR.
• Median progression free survival (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).¹ 
  • In the BsAb cohort, the median PFS was NR.

Safety

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

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.¹ 
• There was no difference in the total CAR-T cell expansion between BsAb and other BT regimens.¹   
• 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).¹ 
• 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.¹ 

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.¹ 
• Patients treated with BsAb had a higher fraction of PD-1+CD8+ and PD-1+CD4+ non-transduced T-cells at leukapheresis.¹ 
• 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.¹ 
• 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.¹ 

Dhakal et al (2024)² conducted a multicenter retrospective study at 14 United States (US) academic medical centers, evaluating patients with RRMM who received TALVEY as BT to BCMA-targeted CAR-T therapy.

Study Design/Methods

• This multicenter retrospective study included patients with RRMM who underwent leukapheresis and received TALVEY BT before commercial ciltacabtagene autoleucel or idecabtagene vicleucel.²
• Safety outcomes included CRS, ICANS, delayed neurotoxicity and TALVEY-related toxicities.²
• Efficacy outcomes assessed were response rates to TALVEY and CAR-T therapies.²

Results

Treatment Disposition/Patient Characteristics

• From June 2023 to May 2024, 77 patients underwent apheresis and received TALVEY BT.²
  • A total of 61 patients underwent successful CAR-T manufacturing, 58 patients (95%) were infused with CAR-T therapy (ciltacabtagene autoleucel n=45 and idecabtagene vicleuce n=13) following TALVEY BT, while 3 patients (5%) died from disease progression before the infusion.
  • There were 6 patients who did not receive CAR-T therapy due to manufacturing failures.
  • There were 10 patients pending CAR-T therapy at the time of last follow-up.
• TALVEY 0.8 mg/kg Q2W was administered to 59 patients (76%), with a median treatment duration of 22 days (interquartile range [IQR]: 10–41 days).²
• Patient characteristics are shown in Table: Patient Characteristics.²

Safety

After receiving TALVEY bridging

• No patients experienced grade ≥3 CRS, and 2 patients (2.5%) experienced grade 3 ICANS.²
• Oral toxicities were reported in 43 patients (56%), skin toxicities in 32 patients (41%), and nail toxicities in 19 patients (25%).²
• By the last follow-up, 60% of oral, skin, and taste-related toxicities had resolved.²
• Of the 58 patients who received CAR-T therapy following TALVEY bridging, 38 patients (65%) experienced CRS, including 2 patients (3%) with grade 3 CRS.²
• ICANS was observed in 5 patients (8.6%), with grade 3 ICANS occurring in 1 patient (1.7%).²
• Delayed neurotoxicity (facial nerve palsy) was reported in 1 patient at the last follow-up.²
• No treatment-related deaths were observed.²

Efficacy

• After receiving TALVEY BT, response to TALVEY was evaluable in 72 of 77 patients, with an overall response observed in 45 patients (62%), including unconfirmed CR in 14 patients, VGPR in 10 patients, and PR in 21 patients.²
• At a median follow-up of 61 days (range, 28–113) after CAR-T treatment, response was evaluable in 40 of the 58 patients.²
  • Responses at day +30 was observed in 39 of 40 patients (97.5%), including 14 in CR, 10 in VGPR, and 15 in PR.

Grajales-Cruz et al³ 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 adverse events, 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.³
• 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.³

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.³       

Safety

• CRS occurred in 11 of 15 patients (73.3%) who received TALVEY BT.³

Waldschmidt et al (2024)⁴ 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 ).⁴
• Patient characteristics are shown in Table: Patient Characteristics.⁴ 

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).⁴
• 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).⁴
• 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).⁴
• 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).⁴
• 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.⁴

Shaikh et al (2024)⁵ 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.⁵
• The IMWG criteria was used to evaluate response to therapy.⁵
• Adverse events were graded based on Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.⁵

Results

Patient Characteristics

• Baseline characteristics for the 13 patients who received TALVEY BT to CAR-T therapy are highlighted in the Table: Baseline Characteristics.⁵ 

Efficacy

• Response rates are shown in the Table: Response to TALVEY Bridging Therapy.⁵   

Safety

• No patients had progressive disease or developed new end-organ damage during BT. At the final data cut-off (July 1, 2024), all patients were alive.⁵
• Adverse events reported in the 13 patients receiving TALVEY as BT is shown in the Table: Incidence of Hematological and Non-hematological Adverse Events for Patients Receiving TALVEY.⁵ 

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 30 January 2025.