SUMMARY

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• Elevated liver enzymes may be a clinical sign or symptom of cytokine release syndrome (CRS). Additional clinical signs and symptoms of CRS may include, but are not limited to, fever, chills, hypotension, tachycardia, hypoxia, and headache.¹
  • Potentially life-threatening complications of CRS may include cardiac dysfunction, adult respiratory distress syndrome, neurological toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
• 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).²
  • 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).²
    • Moreau et al (2022)² published the incidence of hepatotoxic events in patients receiving TECVAYLI in the MajesTEC-1 study. At a median follow-up of 14.1 months, 1 death was reported due to hepatic failure and considered by investigators to be TECVAYLI-related.
• 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).³
  • Cohort E included 32 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO^® (daratumumab and hyaluronidase) and lenalidomide (Tec-DR).⁴
    • Searle et al (2022)⁴ presented the incidence of hepatotoxic events at a median follow-up of 8.4 months. Elevated alanine aminotransferase (ALT; any grade) was reported in 28.1% of patients, with grade 3 or 4 elevations reported in 9.4% 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).⁵ 
  • Costa et al (2025)^5,6 published the incidence of hepatotoxic events from the MajesTEC-3 study. At a median follow-up of 34.5 months, 1 death due to fulminant hepatitis was reported in the Tec-Dara SC arm, and 1 death due to hepatic failure was reported in the DPd/DVd arm.
• 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).⁷
  • Raab et al (2025)⁸ presented the incidence of hepatotoxic events from the 3 induction cohorts of arm A (Tec [weekly; QW]-DR; n=10), arm A1 (Tec [once every 4 weeks; 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.
    • Any-grade elevated gamma-glutamyl transferase (GGT), blood alkaline phosphatase (BAP), and ALT treatment-emergent adverse events (TEAEs) were reported in 28.6%, 16.3%, and 14.3% of patients overall, respectively. Grade 3/4 elevated GGT, BAP, and ALT TEAEs were reported in 14.3%, 2%, and 6.1% of patients, respectively.

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.

clinical data - MAJESTEC-1 STUDY

MajesTEC-1 (NCT03145181; NCT04557098) is evaluating the safety and efficacy results of TECVAYLI in patients with RRMM.²

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 of TECVAYLI at the RP2D; part 3 (the phase 2 component) to evaluate the safety and efficacy of TECVAYLI at the RP2D.^2,9

• Key eligibility criteria for cohort A: measurable MM, RRMM, ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 mAb; no prior B-cell maturation antigen (BCMA)-targeted therapy use.²

Cohort A Safety Results

Moreau et al (2022)^2,10 published the incidence of hepatotoxic events in patients receiving TECVAYLI in the MajesTEC-1 study at a median follow-up of 14.1 months (range, 0.3-24.4).

• An increase in BAP was reported in 10.9% of patients (18/165); grade 3/4 events were reported in 1.8% of patients (3/165).
• Hepatic failure was reported as a fatal adverse event (AE) in 0.6% of patients (1/165) and was considered related to TECVAYLI.

clinical data - Majestec-2 Study

MajesTEC-2 (NCT4722146) 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.³

Study Design/Methods

• Key eligibility criteria for cohort E (Tec-DR): received 1-3 prior LOTs including a PI, and an immunomodulatory drug, and no prior BCMA-targeted therapy.⁴

Cohort E Safety Results

Searle et al (2022)⁴ presented the incidence of hepatotoxic events in cohort E of the MajesTEC-2 study at a median follow-up of 8.4 months (range, 1.1-12.9).

• At a median follow-up of 8.4 months (range, 1.1-12.9), elevated ALT (any grade) was reported in 28.1% of the patients (n=9), with grade 3 or 4 elevations reported in 9.4% of patients (n=3).

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.⁵

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 0-2.⁵

Safety Results

Costa et al (2025)^5,6 published the incidence of hepatotoxic events from MajesTEC-3 study at a median follow-up of 34.5 months (range, 0.03 to 45.3).

• In the Tec-Dara SC arm, fulminant hepatitis led to death in 0.4% of patients (1/283), which was assessed as treatment related.
• In the DPd/DVd arm, hepatic failure led to death in 0.3% of patients (1/290), which was assessed as treatment related.

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.⁷

Study Design/Methods

• Key eligibility criteria: patients with NDMM per 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).⁷

Safety Results

Raab et al (2025)⁸ presented the incidence of hepatotoxic events from 3 induction cohorts of the MajesTEC-5 study at a median follow-up of 7.3 months (range, 3.1-14.5).

• Details on hepatotoxic TEAEs in the 3 induction cohorts are provided in Table: MajesTEC-5 Study: Summary of Hepatotoxic TEAEs.

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 14 January 2026.