SUMMARY

• Janssen does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• MajesTEC-1 (MMY1001) is a phase 1/2, multicohort study evaluating the efficacy and safety of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1-4
  • Cohort A (triple-class exposed) included 165 patients who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody.³
    • At a median follow-up of 14.1 months, lower response rates were observed in the 28 patients (17.0%) with extramedullary disease (EMD). A response was reported in 10/28 patients with EMD (overall response rate [ORR], 35.7% [95% confidence interval (CI), 18.6-55.9]) vs 94/137 patients without EMD (ORR, 68.6% [95% CI, 60.1-76.3]).^3,5
    • Costa et al (2024)⁶ presented a subgroup analysis of the MajesTEC-1 study, evaluating efficacy and safety in patients with high-risk (HR) features, including patients with EMD (n=28). As of the data cutoff on August 22, 2023, the ORR was 63.0% for all patients and 35.7% in patients with EMD. Any grade treatment-emergent adverse events (TEAEs) were reported in 100% of patients with EMD; 92.9% were grade 3/4.
  • Cohort C included 40 patients previously treated with a PI, an immunomodulatory agent, an anti-CD38 monoclonal antibody and anti-B-cell maturation antigen (BCMA)-targeted therapies.⁴
    • Touzeau et al (2024)⁴ published efficacy and safety results from Cohort C of the MajesTEC-1 study. At a median follow-up of 28.0 months, ORR was 52.5% for all patients and 58.3% in patients with EMD.
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY^® (talquetamab-tgvs) and TECVAYLI combination in patients with RRMM.^7-10
  • Cohen et al (2025)^10,11 published efficacy and safety results from the phase 1 dose-escalation segment of the RedirecTT-1 study.
    • All dose levels (dose levels 1-5; N=94): At a median follow-up of 20.3 months, the ORR was 78% for all patients and 58.8% in patients with EMD.
• Dima et al (2024)¹² presented the results from a multicenter, retrospective, real-world study evaluating the efficacy and safety of TECVAYLI vs chimeric antigen receptor (CAR)-T cell therapy for the treatment of patients with RRMM and EMD. ORR was 47% vs 77% in the TECVAYLI vs CAR-T cell groups.
• Riedhammer et al (2024)¹³ conducted an investigator-initiated, multicenter, retrospective, real-world study evaluating the efficacy and tolerability of TECVAYLI in patients with RRMM. Significantly lower ORR and median progression-free survival (PFS) were observed in patients with EMD than in those with no EMD (P<0.01).
• Joiner et al (2023)¹⁴ reported a preliminary experience evaluating the efficacy and safety of TECVAYLI in patients with RRMM and severely impaired renal function. Among the 7 patients included in their analysis, 2 patients presented with extramedullary plasmacytomas and showed disease progression leading to treatment discontinuation before the second cycle.
• Venkatesh et al (2023)¹⁵ presented the results of a retrospective, real-world study evaluating the safety and efficacy of TECVAYLI in patients with RRMM. Among the 14 patients with EMD included in the study, ORR was 28%.
• Other relevant literature has been identified in addition to the data summarized above.¹⁶

PRODUCT LABELING

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

CLINICAL DATA - MAJESTEC-1 STUDY

MajesTEC-1 (MMY1001; clinicaltrials.gov identifiers: NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.^1-4

Study Design/Methods

The main objectives are as follows: part 1 (dose escalation), to determine the recommended phase 2 dose (RP2D) for TECVAYLI; part 2 (dose expansion), to distinguish safety and tolerability at the RP2D; and part 3 (phase 2 component), to evaluate the efficacy of TECVAYLI at the RP2D.^3,17

• Key eligibility criteria:
  • Cohort A: ≥3 prior lines of therapy, including a PI, an immunomodulatory drug, and an anti-CD38 mAb, and no prior BCMA-targeted therapy use.³
  • Cohort C: ≥3 prior lines of therapy, a prior PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, enrolled patients who had prior exposure to BCMA-targeted treatment (CAR-T cell and/or antibody drug conjugate [ADC]).⁴
• Primary endpoint for Cohort A and Cohort C: ORR.^3,4
• Key secondary endpoint for Cohort A and Cohort C: safety.^3,4

Cohort A Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• At a median follow-up of 14.1 months (range, 0.3-24.4), 165 patients received TECVAYLI at recommended phase 2 dose (RP2D): 40 patients in phase 1 and 125 patients in phase 2.³
• EMD, defined as the presence of ≥1 extramedullary soft tissue lesions not associated with bone, was present in 28 patients (17.0%): 8 patients (20%) in phase 1 and 20 patients (16.0%) in phase 2.³

Efficacy

• At a median follow-up of 14.1 months (range, 0.3-24.4), ORR in the total population was 63.0% (95% CI, 55.2-70.4).³
• Lower response rates were observed in patients with EMD.³
• Responses were reported in 10/28 patients with EMD (ORR, 35.7% [95% CI, 18.6-55.9]) vs 94/137 patients without EMD (ORR, 68.6% [95% CI, 60.1-76.3]).⁵

Safety

• These publications did not report on the safety profile of TECVAYLI in the subpopulation of patients with EMD.

Costa et al (2024)⁶ presented a subgroup analysis from the MajesTEC-1 study evaluating efficacy and safety in patients with HR features. Results specific to the EMD sub-group are summarized below.

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• At a data cutoff of Aug 22, 2023, a total of 165 patients had received TECVAYLI at the RP2D.
• EMD, defined as the presence of ≥1 soft tissue plasmacytoma with no contact with bony structures, was present in 28 patients (17.0%).

Efficacy

• Select efficacy outcomes including response rates and duration of response (DOR) were evaluated. Response rates in overall population and in patients with EMD are presented in Table: MajesTEC-1 (Cohort A) Study: Summary of ORR. Details on DOR in patients in overall population and in patients with EMD are provided in MajesTEC-1 (Cohort A) Study: DOR to TECVAYLI.

Safety

• A summary of safety outcomes in overall population and in patients with EMD is provided in Table: MajesTEC-1 (Cohort A) Study: Summary of Safety Outcomes.

Cohort C Results

Touzeau et al (2024)⁴ published efficacy and safety results from Cohort C of the MajesTEC-1 study at a median follow-up of 28.0 months (range, 0.7-31.1).

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 40 patients received TECVAYLI with a median duration of treatment of 6.0 months (range, 0.2-29.8).
• EMD, defined as the presence of ≥1 extramedullary soft tissue plasmacytomas not associated with bone, was present in 12 patients (30%).

Efficacy

• ORR was 52.5% for all patients and 58.3% in patients with EMD.

Safety

• These data did not report on the safety profile of TECVAYLI in the subpopulation of patients with EMD.

clinical data - REDIRECTT-1 study - TALVEY + TECVAYLI COHORT

RedirecTT-1 (MMY1003; clinicaltrials.gov identifier: NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and effectiveness of the combination of TALVEY and TECVAYLI in patients with RRMM.^7-10

Study Design/Methods

• Key eligibility criteria: relapsed or refractory or intolerant to established therapies including the last LOT, prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^7,10
• Primary endpoints: dose limiting toxicity and ORR.^7,10

Cohen et al (2025)^10,11 published efficacy and safety results from the phase 1 dose-escalation segment of the RedirecTT-1 study across all dose levels (dose levels 1-5).

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• At a median follow-up of 20.3 months (range, 0.5-37.1), 94 patients in the all-dose-levels cohort received TALVEY and TECVAYLI; at a median follow-up of 18.2 months (range, 0.7-27.0), 44 patients received the RP2R.
• EMD, defined as ≥1 nonradiated, bone-independent lesion ≥2 cm, was present in 34 patients (36%) in the all dose levels cohort and 18 patients (41%) in the RP2R cohort. EMD was assessed by physical examination every 4 weeks and radiologic assessment every 12 weeks.

Efficacy

• At a median follow up of 20.3 months (range, 0.5-37.1), ORR was 78% for all patients.
• Efficacy outcomes in all dose levels, dose levels 1-4, and RP2R cohorts in patients with EMD are presented in Table: RedirecTT-1 Study (TALVEY + TECVAYLI Cohort): Response Summary in Patients With EMD.

Safety

• This publication did not report on the safety profile of TECVAYLI in the subpopulation of patients with EMD.

CLINICAL DATA - REAL-WORLD STUDIES

Dima et al (2024)¹² presented the results from a multicenter, retrospective, real-world study evaluating the efficacy and safety of TECVAYLI vs CAR-T cell therapy for the treatment of patients with RRMM and EMD.

Study Design/Methods

• Patients with RRMM who had a known history of EMD or currently had EMD, including those who had undergone apheresis up until August 15, 2023, received either TECVAYLI or CAR-T cell therapy.

Results

• A total of 110 patients from 3 United States (US) academic centers (part of the US Myeloma Innovations Research Collaborative [USMIRC]) who received TECVAYLI (n=45), or CAR-T cell therapy (n=65) were included.
• The median follow-up for the entire group was 5 months (range, 0.5-22).
• In the TECVAYLI vs CAR-T cell group, patients received a median of 6 (range, 4-14) vs 6 (range, 4-15) prior lines of therapy, 93% vs 88% of patients had triple-class refractory disease, and 55.5% vs 15% of patients had received prior BCMA-directed therapy.

Efficacy

• Efficacy data are reported in Table: Summary of Efficacy Data.

Safety

• Safety data are reported in Table: Summary of Safety Data.

Riedhammer et al (2024)¹³ conducted an investigator-initiated, multicenter, retrospective, real-world study evaluating the efficacy and tolerability of TECVAYLI in patients with RRMM.

Study Design/Methods

• Patients who had received ≥1 full treatment dose of TECVAYLI between July 2022 and October 2023 at 18 German centers were included.
• Patients received TECVAYLI 1.5 mg/kg QW as per the label, after step-up doses (SUDs) of 0.06 mg/kg and 0.3 mg/kg.
• Patients were retrospectively assessed for the fulfillment of select key inclusion criteria of the MAJESTEC-1 study at screening.
• Outcomes were assessed per the International Myeloma Working Group (IMWG) response criteria.

Results

• A total of 123 patients (median age, 67 years [range, 35.0-87.0]) were included in the study; 43 of 119 patients (36.1%) had EMD.

Efficacy

• At a median follow-up of 5.5 months, ORR was 59.3% and median PFS was 8.7 months for all patients.
• Significantly lower ORR and median PFS were observed in patients with EMD than in those with no EMD (P<0.01). See Tables: Median PFS in the EMD Subgroup Assessed via Univariable and Multivariable Models and ORR in the EMD Subgroup Assessed via Univariable Model.

Safety

• These data did not report on the safety profile of TECVAYLI in the subpopulation of patients with EMD.

Joiner et al (2023)¹⁴ reported a preliminary experience evaluating the efficacy and safety of TECVAYLI in patients with RRMM and severely impaired renal function.

Study Design/Methods

• The Food and Drug Administration (FDA)-approved TECVAYLI prescribing information dosing schedule was followed for dosing cycles 1 and 2. At dosing cycle 3, the frequency was modified to every 2 weeks (Q2W) for 8 doses followed by every 4 weeks (Q4W) starting cycle 7 onward.
• Mitigation for infection included oral levofloxacin; prophylaxis for Herpes simplex virus/varicella zoster virus and Pneumocystis jirovecii, started at the onset of TECVAYLI therapy.

Results

• A total of 7 patients were included in the study; 2 patients had extramedullary plasmacytomas. See Table: Characteristics of 2 Patients with RRMM, Severe Renal Impairment, and Extramedullary Plasmacytomas Treated with TECVAYLI.

Efficacy

• Two patients with extramedullary plasmacytomas showed disease progression leading to treatment discontinuation before the second cycle. See Table: Summary of Efficacy Outcomes.

Safety

• One patient (patient number 5), who had extramedullary plasmacytoma, experienced grade 3 CRS with TECVAYLI.
• No immune effector cell-associated neurotoxicity syndrome (ICANS) or infections were reported.

Venkatesh et al (2023)¹⁵ presented the results of a retrospective, real-world study evaluating the safety and efficacy of TECVAYLI in patients with RRMM, including those who were ineligible for enrollment in the MajesTEC-1 study.

Study Design/Methods

• Electronic medical records of patients with RRMM who had received TECVAYLI at the University of Kansas Health System as of February 10, 2023, was retrospectively reviewed in collaboration with USMIRC.
• Responses were evaluated using the IMWG criteria.

Results

• A total of 22 patients were included in the study; 14 patients (64%) had EMD.

Efficacy

• At the median follow-up of 3.1 months (range, 1.7-4.1), ORR was 50% for the evaluated population, and was 28% in patients with EMD.

Safety

• These data did not report on the safety profile of TECVAYLI in the subpopulation of patients with EMD.

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 13 February 2025.