SUMMARY

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• This response provides relevant data from company-sponsored clinical trials, and the content is limited to the studies included below.
• MajesTEC-1 is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).¹
  • Cohort A (triple-class exposed) included 165 patients previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody (mAb).¹
    • Nooka et al (2023)² published the incidence, timing, and management of hypogammaglobulinemia in patients receiving TECVAYLI in the MajesTEC-1 study. At a median follow-up of 22.8 months, hypogammaglobulinemia was reported in 71.5% of patients overall.
    • Garfall et al (2024)³ presented the incidence of hypogammaglobulinemia at a median follow-up of 30.4 months. Hypogammaglobulinemia was reported in 21.8% of patients; grade 3/4 hypogammaglobulinemia was reported in 1.8% of patients.
  • Cohort C included 40 patients previously treated with a PI, an immunomodulatory agent, an anti-CD38 mAb and anti-B-cell maturation antigen (BCMA)-targeted therapies.⁴
    • Touzeau et al (2024)⁴ published the incidence of hypogammaglobulinemia at a median follow-up of 28.0 months. Hypogammaglobulinemia was reported in 15% of patients.
• MajesTEC-2 is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer therapies in patients with multiple myeloma (MM).⁵
  • Cohort A included 17 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO^® (daratumumab and hyaluronidase) and pomalidomide.⁶
    • D’Souza et al (2024)⁶ presented the incidence of hypogammaglobulinemia at a median follow-up of 16.2 months. Hypogammaglobulinemia was reported in 94.1% of patients.
  • Cohort C included 28 patients with RRMM who received TECVAYLI and nirogacestat.⁷
    • Offner et al (2023)⁷ presented the incidence of hypogammaglobulinemia at a median follow-up of 14.7 months. Hypogammaglobulinemia was reported in 28.6% of patients; grade 3/4 hypogammaglobulinemia was reported in 7.1% of patients.
• MajesTEC-3 is a phase 3, randomized, open-label study evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO (Tec-Dara subcutaneous [SC]) vs investigator’s choice of DARZALEX FASPRO, pomalidomide, and dexamethasone (DPd) or DARZALEX FASPRO, bortezomib, and dexamethasone (DVd) in patients with RRMM after 1-3 prior lines of therapy (LOTs).⁸
  • Costa et al (2025)⁸ published the incidence of hypogammaglobulinemia from the MajesTEC-3 study. At a median follow-up of 34.5 months, hypogammaglobulinemia was reported in 84.5% of patients in the Tec-Dara SC arm and 60.3% in the DPd/DVd arm.
• MajesTEC-4 is an open-label, randomized, multicenter, phase 3 study assessing the safety and efficacy of TECVAYLI in combination with lenalidomide (Tec-Len) and TECVAYLI alone vs lenalidomide alone as maintenance therapy after an autologous stem cell transplant (ASCT) in patients with newly diagnosed multiple myeloma (NDMM).⁹ 
  • Zamagni et al (2024)⁹ presented the incidences of hypogammaglobulinemia from a safety-run in (SRI) consisting of 3 cohorts.
    • Cohort 1 (Tec-Len; TECVAYLI weekly [QW] to once every 4 weeks [Q4W]; N=32): At a median follow-up of 21.1 months, hypogammaglobulinemia was reported in 96.9% of patients.
    • Cohort 2 (Tec-Len; TECVAYLI Q4W; N=32): At a median follow-up of 9.2 months, hypogammaglobulinemia was reported in 78.1% of patients.
    • Cohort 3 (TECVAYLI Q4W; N=30): At a median follow-up of 9.2 months, hypogammaglobulinemia was reported in 93.3% of patients.
• MajesTEC-5 is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI-based combination regimens in patients with transplant-eligible newly diagnosed multiple myeloma (TE-NDMM).¹⁰
  • Raab et al (2025)¹¹ presented the incidence of hypogammaglobulinemia from the 3 induction cohorts of arm A (TECVAYLI QW in combination with DARZALEX FASPROand lenalidomide; Tec [QW]-DR; n=10), arm A1 (Tec [Q4W]-DR; n=20), and arm B (Tec Q4W in combination with DARZALEX FASPRO, bortezomib, and lenalidomide; Tec [Q4W]-DVR; n=19) in the MajesTEC-5 study at a median follow-up of 7.3 months (range, 3.1-14.5).
    • Hypogammaglobulinemia was reported in 91.8% of patients overall.
• MajesTEC-7 is a randomized, phase 3 study comparing the safety and efficacy of Tec-DR and TALVEYin combination with DARZALEX FASPRO and lenalidomide (Tal-DR) vs DARZALEX FASPRO in combination with lenalidomide and dexamethasone (DRd) in patients with NDMM who are ineligible or not intended for transplant as initial therapy.¹²
  • Touzeau et al (2024)¹² presented the incidence of hypogammaglobulinemia from SRI cohort 1 (TEC-DR) at a median follow-up of 13.8 months. Hypogammaglobulinemia was reported in 80.8% of patients.
• TRIMM-2 is an ongoing, phase 1b, multicohort study evaluating the safety and efficacy of DARZALEX FASPRO regimens in combination with bispecific T-cell redirecting antibodies in patients with RRMM.¹³
  • D’Souza et al (2024)⁶ presented the incidence of hypogammaglobulinemia in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort (N=10) at a median follow-up of 38.3 months. Hypogammaglobulinemia was reported in 100% of patients.

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.
• 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-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 (NCT03145181; NCT04557098) is evaluating the safety and efficacy of TECVAYLI in patients with RRMM.¹

Study Design/Methods

The main objectives are as follows: part 1 (dose escalation) to determine the RP2D for TECVAYLI; part 2 (dose expansion) to distinguish safety and tolerability at the RP2D; and part 3 (the phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^1,14

• Key eligibility criteria:
  • Cohort A: ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 mAb, no prior BCMA-targeted therapy use.¹
  • Cohort C: ≥3 prior LOTs, a prior PI, an immunomodulatory drug, and an anti-CD38 mAb, enrolled patients who had prior exposure to BCMA-targeted treatment (chimeric antigen receptor [CAR-T] therapy and/or antibody drug conjugate [ADC]).⁴

Cohort A Safety Results

Nooka et al (2023)² published the incidence, timing, and management of hypogammaglobulinemia in patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 22.8 months (range, 0.3-33.6); data cutoff date of January 4, 2023.

• Hypogammaglobulinemia was reported in 71.5% of patients (n=118) overall (hypogammaglobulinemia defined as an adverse event (AE), laboratory IgG value <400 mg/dL, or both).
• A total of 21.2% of patients (n=35) reported hypogammaglobulinemia as an AE.
• A total of 70.9% of patients (n=117) had ≥1 postbaseline IgG value <400 mg/dL.
  • IgG MM was reported in 60.4% of patients and non-IgG MM was reported in 83.8% of patients.
• No patients discontinued TECVAYLI treatment due to hypogammaglobulinemia.
• Median time to IgG <400 mg/dL was 1.2 months (range, 0.2-19.8).
• A total of 46.1% of patients (n=76) received IgG replacement (prophylaxis and management). Of these, 35.2% of patients received IV only, 3.6% of patients received SC only, 0.6% of patients received intramuscular (IM) only, and 6.7% of patients received ≥1 route of administration.
  • A total of 6.1% of patients started IgG replacement prior to receiving TECVAYLI, including 5.5% of patients who started before TECVAYLI treatment and continued throughout the treatment period.
• Decreased IgG, IgA, and IgM levels were observed in patients across MM subtypes at baseline. See Table: MajesTEC-1 (Cohort A): Proportion of Patients with Immunoglobulin Depletion at Baseline Across IgG, IgA and IgM MM Subtypes.²

Recommendations for Management of Hypogammaglobulinemia

• IgG levels should be monitored every 4-6 weeks. IgG replacement (0.4 g/kg, intravenous [IV] or SC) should be used to maintain serum IgG levels ≥400 mg/dL every 3-6 weeks. After steady state is reached, measure IgG levels every 3 months.
• IgG replacement should be administered per institutional guidelines for life-threatening infections (especially from encapsulated bacteria), for serious or recurrent/chronic infections, and prophylactically based on physician-assessed clinical benefit.
• Serum IgG testing and/or serum protein electrophoresis during disease status evaluation might be altered due to IgG replacement.

Garfall et al (2024)³ presented the incidence of hypogammaglobulinemia at a median follow-up of 30.4 months.

• Hypogammaglobulinemia (as an AE, any grade) was reported in 21.8% of patients (n=36); grade 3/4 hypogammaglobulinemia was reported in 1.8% of patients (n=3).

Cohort C Safety Results

Touzeau et al (2024)⁴ published the incidence of hypogammaglobulinemia in cohort C of the MajesTEC-1 study at a median follow-up of follow-up of 28.0 months (range, 0.7-31.1).

• Hypogammaglobulinemia (as an AE, any grade) was reported in 15% of patients (n=6).
• Of the 31 patients (77.5%) with evidence of hypogammaglobulinemia, 16 patients (40.0%) received intravenous immunoglobulin (IVIG) treatment at any time during the study according to institutional guidelines.

clinical data - Majestec-2 Study

MajesTEC-2 (NCT04722146) is an ongoing, phase 1b, multicohort, open-label study evaluating the safety and efficacy of TECVAYLI in combination with other anticancer treatments in patients with MM.⁵

Study Design/Methods

Key Eligibility Criteria

• Cohort A (TECVAYLI and DARZALEX FASPRO and pomalidomide): received 1 to 3 prior LOT, including a PI and lenalidomide.⁶
• Cohort C (TECVAYLI and nirogacestat): disease progression within 12 months of last LOT; ≥3 prior LOTs or double refractory to a PI, and an immunomodulatory drug and triple-class exposed to a PI, an immunomodulatory drug, and an anti-CD38 mAb. Patients with prior exposure to BCMA-targeted therapy were permitted.^5,7

Cohort A Safety Results

D’Souza et al (2024)⁶ presented the incidence of hypogammaglobulinemia in cohort A of the MajesTEC-2 study at a median follow-up of 16.2 months (range, 0.5-34.5).

• Hypogammaglobulinemia (reported as an AE or postbaseline IgG <400 mg/dL) was reported in 94.1% of patients (n=16). A total of 70.6% of patients (n=12) received IVIG. Of note, study enrollment began before IVIG was routinely recommended for patients treated with bispecific antibodies (March 2021 to August 2021).

Cohort C Safety Results

Offner et al (2023)⁷ presented the incidence of hypogammaglobulinemia in cohort C of the MajesTEC-2 study at a median follow-up of 14.7 months (range, 0.5-22.9).

• Hypogammaglobulinemia (as an AE, any grade) was reported in 8 patients (28.6%); grade 3/4 hypogammaglobulinemia was reported in 2 patients (7.1%).
• A hypogammaglobulinemia treatment-emergent adverse event (TEAE) or ≥1 postbaseline IgG value of <500 mg/dL, was reported in 78.6% of patients. Of these, 42.9% of patients were administered IVIG treatment.

clinical data - majestec-3 study

MajesTEC-3 (NCT05083169) is a phase 3, randomized, open-label study evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO vs DPd or DVd (investigator’s choice) in patients with RRMM after 1-3 prior LOTs.⁸

Study Design/Methods

• Key eligibility criteria: RRMM, 1-3 prior LOTs, including a PI and lenalidomide, patients with only 1 prior LOT must have been lenalidomide-refractory per International Myeloma Working Group criteria, and Eastern Cooperative Oncology Group performance status 0-2.⁸

Safety Results

Costa et al (2025)⁸ published the incidence of hypogammaglobulinemia from the MajesTEC-3 study at a median follow-up of 34.5 months (range, 0.03 to 45.3).

• Hypogammaglobulinemia was reported in 84.5% of patients (239/283) in the Tec-Dara SC arm and 60.3% (175/290) in the DPd/DVd arm.
• At least 1 dose of immune globulin was administered to 87.3% of patients (247/283) in the Tec-Dara SC arm and 44.8% (130/290) in the DPd/DVd arm.

CLINICAL DATA - MajesTEC-4 study

MajesTEC-4 (NCT05243797) is an open-label, randomized, multicenter, phase 3 study evaluating the safety and efficacy of Tec-Len and TECVAYLI alone vs lenalidomide alone as maintenance therapy in patients with NDMM.⁹

Study Design/Methods

SRI Cohorts

• A SRI period consisting of 3 cohorts was used to establish safety prior to enrolling the randomized phase of the study.⁹
• Maintenance regimen (2-year fixed duration): patients who achieved a complete response (CR) on Tec-Len after 1-year discontinued TECVAYLI and continued lenalidomide for an additional year.⁹
• Key eligibility criteria: NDMM, receipt of 4 to 6 cycles of 3- or 4-drug induction therapy (PI and/or immunomodulatory drug ± anti-CD38 mAb), and ASCT (single or tandem ASCT permitted) ± consolidation with partial response (PR) or better.⁹

Safety Results

Zamagni et al (2024)⁹ presented the incidence of hypogammaglobulinemia from SRI cohort 1 (Tec-Len; TECVAYLI QW to Q4W) at a median follow-up of 21.1 months (range, 14.8-23.8), SRI cohort 2 (Tec-Len; TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 1.2-12.2), and SRI cohort 3 (TECVAYLI Q4W) at a median follow-up of 9.2 months (range, 3.7-11.5).

• Hypogammaglobulinemia (including patients with ≥1 TEAE of hypogammaglobulinemia or postbaseline IgG <400 mg/dL) was reported in 96.9% of patients (n=31) in cohort 1, 78.1% of patients (n=25) in cohort 2, and 93.3% of patients (n=28) in cohort 3. All patients received ≥1 dose of IVIG or subcutaneous immunoglobulin (SCIg).
• Prophylactic IVIG replacement was advised to maintain serum IgG levels of ≥400 mg/dL.

CLINICAL DATA - MajesTEC-5 study

MajesTEC-5 (GMMG-HD10; DSMM-XX) is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI-based combination regimens in patients with TE-NDMM.¹⁰

Study Design/Methods

• Key eligibility criteria: patients with NDMM per International Myeloma Working Group (IMWG) criteria and measurable disease; highdose therapy (HDT) and ASCT intended (except arms D and G). Arm C/C2 only: received 4-6 cycles of 28‑day PI‑ and/or immunomodulatory‑based induction ± anti‑CD38 mAb and a single/tandem ASCT, 1 prior LOT, at least a PR per IMWG 2016 criteria, and HDT/ASCT within 12 months of induction start and within 6 months of last ASCT (7 months with consolidation).¹⁰

Safety Results

Raab et al (2025)¹¹ presented the incidence of hypogammaglobulinemia from 3 induction cohorts of the MajesTEC-5 study at a median follow-up of 7.3 months (range, 3.1-14.5).

• Hypogammaglobulinemia (including patients with ≥1 TEAE of hypogammaglobulinemia or post-baseline IgG <400 mg/dL) was reported in 91.8% of patients (n=45).
  • A total of 89.8% of patients (n=44) received ≥1 dose of IVIG.

clinical data - Majestec-7 Study - TECVAYLI + TALVEY COHORT

MajesTEC-7 (NCT05552222) is a randomized, phase 3 study comparing the safety and efficacy of Tec-DR and Tal-DR vs DRd in patients with NDMM who are ineligible or not intended for transplant as initial therapy.¹²

Study Design/Methods

SRI Cohort 1 (Tec-DR)

• A SRI period was used to establish safety prior to enrolling in the randomized phase of the study.¹²
• Key eligibility criteria: NDMM either ineligible or not intended for ASCT.¹²

Safety Results

Touzeau et al (2024)¹² presented the incidence of hypogammaglobulinemia from the SRI of 26 patients in cohort 1 (Tec-DR) of the MajesTEC-7 study at a median follow-up of 13.8 months (range, 2.0-15.4).

• Hypogammaglobulinemia (including patients with ≥1 treatment-emergent hypogammaglobulinemia or postbaseline IgG <500 mg/dL) was reported in 80.8% of patients (n=21). Overall, 73.1% of patients (n=19) received at least 1 dose of IVIG.

clinical data - Trimm-2 study - TECVAYLI + TALVEY COHORT

TRIMM-2 (NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating the safety and efficacy of DARZALEX FASPRO regimens in combination with bispecific T-cell redirection antibodies in patients with RRMM.¹⁵

Study Design/Methods

• Key eligibility criteria: ≥3 prior LOTs (including a PI and an immunomodulatory drug) or double refractory to a PI and an immunomodulatory drug, anti-CD38 mAb >90 days prior allowed, prior bispecific antibody (BsAb) and CAR-T were allowed.¹⁵

Safety Results

D'Souza et al (2024)⁶ presented the incidence of hypogammaglobulinemia in the TECVAYLI + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 38.3 months (range, 1.2-39.6).

• Hypogammaglobulinemia (as an AE, any grade or postbaseline IgG <400 mg/dL) was reported in 100% of patients; 80% of patients (n=8) received IVIG.
• Study enrollment began before IVIG was routinely recommended for patients treated with bispecific antibodies (November 2020 to March 2021).

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 27 January 2026.