SUMMARY

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• Routine pharmacovigilance surveillance activities in Johnson & Johnson are in place to detect safety signals, both clinical and spontaneous events as a standard part of our processes. Confirmed signals are communicated as appropriate with health authorities and investigators/healthcare professionals (HCPs) in a timely manner.
• Cardiovascular adverse events (CVAEs) have been reported in the MajesTEC-1 and MajesTEC-3 studies.^1-4
• MajesTEC-1 is a phase 1/2, multicohort study evaluating the efficacy and safety of TECVAYLI in patients with relapsed/refractory multiple myeloma (RRMM).⁵
  • Cohort A (triple-class exposed) included 165 patients with RRMM who were previously treated with a proteasome inhibitor (PI), an immunomodulatory agent, and an anti-CD38 monoclonal antibody (mAb).⁵
    • Details on cardiovascular treatment-emergent adverse events (TEAEs) are presented in the Table: MajesTEC-1 Study (Cohort A): Incidence of Cardiovascular TEAEs.¹
  • Cohort C included 40 patients with RRMM, previously treated with a PI, an immunomodulatory agent, an anti-CD38 mAb and anti-B-cell maturation antigen (BCMA)-targeted therapies.⁶
    • Details on cardiovascular TEAEs are presented in the Table: MajesTEC-1 Study (Cohort C): Incidence of Cardiovascular TEAEs.²
• 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).³ 
  • Costa et al (2025)^3,4 published the cardiovascular TEAEs from the MajesTEC-3 study. At a median follow-up of 34.5 months, 1 death due to enterovirus myocarditis and 1 due to acute myocardial infarction were reported in the Tec-Dara SC arm, and 1 death due to cardiac failure was reported in the DPd/DVd arm.
• Lee et al (2025)⁷ presented a retrospective, multicenter cohort study evaluating the real‑world incidence of CVAEs in patients with RRMM treated with TECVAYLI. At a median followup of 20.1 months, major adverse cardiovascular events (MACE) and arrhythmias were each reported in 7.3% of patients, with 12.8% experiencing any MACE or arrhythmia. MACE was reported in 16.4% of patients with baseline cardiovascular disease (CVD) and 2.7% of patients without baseline CVD.
• Barbieri et al (2025)^8,9 evaluated new unexpected signals of disproportionate reporting (SDRs) for CV and respiratory AEs associated with mAbs (including TECVAYLI) used in the treatment of MM using the Food and Drug Administration Adverse Event Reporting System (FAERS) database.
• Sayed et al (2024)¹⁰ published a postmarketing surveillance study that reported the frequency and association of CVAEs with bispecific T-cell engagers (BTEs), their prognostic implications on patients receiving BTEs, and the extent of their overlap with cytokine release syndrome (CRS) by using the FAERS database.
• Stepanovic et al (2023)¹¹ presented results from a single-center, retrospective study that evaluated real-world treatment outcomes in patients with RRMM who received TECVAYLI. One unexplained sudden cardiac death was reported.

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 of TECVAYLI in patients with RRMM.⁵

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 (phase 2 component), to evaluate the efficacy of TECVAYLI at the RP2D.^5,12
• Key eligibility criteria:
  • Cohort A: ≥3 prior LOTs, including a PI, an immunomodulatory drug, and an anti-CD38 mAb, and no prior BCMA-targeted therapy use.⁵
  • 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 cell and/or antibody drug conjugate [ADC]).⁶

Cohort A Safety Results

• Cardiovascular TEAEs reported at a median follow-up of 30.4 months (range, 0.3 - 41.5), are shown in Table: MajesTEC-1 Study (Cohort A): Incidence of Cardiovascular TEAEs.¹

Cohort C Safety Results

• Cardiovascular TEAEs reported at a median follow-up of 28.0 months (range, 0.7-31.1) are shown in Table: MajesTEC-1 Study (Cohort C): Incidence of Cardiovascular TEAEs.²

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.³

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 0-2.³

Safety Results

Costa et al (2025)^3,4 published the incidence of cardiovascular TEAEs 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, death due to enterovirus myocarditis was reported in 0.4% of patients (1/283), this death was assessed as treatment related, and death due to acute myocardial infarction in 0.4% of patients (1/283).
• In the DPd/DVd arm, death due to cardiac failure was reported in 0.3% of patients (1/290).
• In the DPd/DVd arm, death due to cerebrovascular accident was reported in 0.3% of patients (1/290).

REAL-WORLD studies

Lee et al (2025)⁷ presented a retrospective, multicenter cohort study evaluating the real‑world incidence of CVAEs in patients with RRMM treated with TECVAYLI.

Study Design/Methods

• This study was conducted at 5 medical centers.
• Baseline oncologic and cardiovascular characteristics were collected, including vital signs and echocardiographic data.
• Baseline CVD was defined as the presence of coronary artery disease, congestive heart failure, severe or symptomatic valvular heart disease, or stroke at baseline.
• CVAEs were collected and categorized using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 by each participating center.
• MACE was defined as a composite of congestive heart failure, asymptomatic cardiomyopathy (interval left ventricular ejection fraction [LVEF] drop >10% to a resultant LVEF less than 50%), coronary artery disease requiring intervention, stroke, or cardiovascular death.
• Arrhythmia was defined as a composite of atrial tachyarrhythmia, ventricular tachyarrhythmia, or bradyarrhythmia.

Results

Patient Characteristics

• The study included 219 patients treated with TECVAYLI; no additional treatment disposition data were reported.
• The median followup duration was 20.1 months.
• ECOG performance status ≥2 was reported in 62.5% of patients with MACE and 27.7% of patients without MACE (P=0.008).
• Baseline hemoglobin was 9 g/dL in patients with MACE and 10 g/dL in patients without MACE (P=0.072).
• There were no differences between patients with and without MACE in age, sex, bone marrow plasma cell burden, ferritin, Creactive protein, or lactate dehydrogenase levels.

Incidence of CVAEs

• MACE was reported in 7.3% of patients (16/219) and arrhythmia in 7.3% of patients (16/219), with 12.8% (28/219) experiencing any MACE or arrhythmia.
• MACE was reported at a median of 4.5 days after TECVAYLI stepup dosing (interquartile range [IQR], 2.25-15.75 days).
• The incidence of MACE was 16.4% in patients with baseline CVD and 2.7% in patients without baseline CVD (P<0.001).

Baseline Hemodynamics and Cardiac Function

• Baseline diastolic blood pressure was 67.7 mm Hg in patients with MACE and 73.8 mm Hg in patients without MACE (P=0.041).
• Baseline LVEF was 51.4% in patients with MACE and 59.3% in patients without MACE (P=0.059).
• Baseline echocardiography was performed in 86% of the overall cohort.

CRS and ICANS

• CRS grade ≥2 occurred in 25% of patients with MACE and 16.7% of patients without MACE (P=0.620).
• ICANS grade ≥2 occurred in 12.5% of patients with MACE and 7.5% of patients without MACE (P=0.812).

Survival Analyses

• In multivariable Cox regression analysis, MACE was associated with overall survival (HR, 2.72; 95% confidence interval [CI], 1.41-5.25; P=0.003) after adjustment for baseline CVD, age, high bone marrow burden, extramedullary disease, and plasma cell leukemia.
• In cause‑specific multivariable Cox regression analysis, MACE was associated with non‑myeloma‑related death (HR, 10.77; 95% CI, 4.39-26.41; P<0.001) and was not associated with myeloma‑related death (HR, 1.54; 95% CI, 0.64-3.70; P=0.336).

Barbieri et al (2025)^8,9 evaluated the FAERS database for unexpected SDRs for CV and respiratory AEs associated with mAbs (including TECVAYLI) used in the treatment of MM.

Study Design/Methods

• A retrospective pharmacovigilance analysis was performed using FAERS data from January 2015 to December 2023.
• Reports listing daratumumab, elotuzumab, isatuximab, belantamab mafodotin, TECVAYLI, elranatamab, or talquetamab as the primary suspect were included, excluding non-MM indications to reduce the confounding risk.
• To analyze CVAEs, reports in FAERS were selected based on Medical Dictionary for Regulatory Activities (MedDRA^®) v26.1 System Organ Classes of "cardiac disorders" and vascular disorders."
• For clinical specificity, Standardized MedDRA Queries (SMQs) were used to identify AEs.
• A descriptive analysis was first performed, followed by a disproportionality analysis using reporting odds ratios (RORs) with two reference groups comparing mAbs to all other drugs (reference group 1 [RG1]) and a sensitivity analysis comparing mAbs to other MM drugs (reference group 1 [RG2]).

Results

• A total of 6,574 reports (0.1% of all FAERS entries) were identified as related to CVAEs and respiratory AEs of which 160 reports (2.4%) were for TECVAYLI.
• The analysis relevant to TECVAYLI is shown in Table: Disproportionality Analyses of Cardiovascular Safety Signals for TECVAYLI Based on FAERS Data.

Limitations

• AEs in FAERS are submitted voluntarily by HCPs and patients, whereas pharmaceutical companies are mandated to report them. As a result, the database may not fully reflect real-world AE occurrences.
• Patient-level data such as demographics and history of cardiovascular conditions are often incomplete or inconsistently recorded.
• Disproportionality analysis is useful for detecting potential safety signals, but does not confirm causality or provide incidence estimates.
• The method is limited in its inability to establish causal relationships between mAbs and reported AEs due to the nature of spontaneous reporting system (SRS data, which lack detailed timelines, causality assessments, and individualized clinical context).
• Several biases and confounding factors must be considered: confounding by indication (cancer and disease severity elevate CV risk), channeling bias (from use in later-line settings), and polypharmacy (common in MM), complicating attribution of AEs to a single agent.
• These limitations necessitate cautious interpretation of findings and may be addressed through case-level evaluations.

Sayed et al (2024)¹⁰ published a postmarketing surveillance study that reported the frequency and association of CVAEs with BTEs, their prognostic implications on patients receiving BTEs, and the extent of their overlap with CRS.

Study Design/Methods

• Adverse event (AE) reports between October 2014 and September 2023 from the United States Food and Drug Administration’s Adverse Event Reporting System (FAERS) were included in this analysis.
• The 5 BTE products included in this analysis were blinatumomab, TECVAYLI, mosunetuzumab, glofitamab, and epcoritamab.
• CVAEs of interest (bleeding, hypotension or shock, thromboembolic disease [including overall thromboembolic events, arterial and venous thromboembolic events, and disseminated intravascular coagulation [DIC]], coronary disease, myocardial infarction, heart failure, conduction abnormalities [including tachyarrhythmia, bradycardia, QT prolongation, and premature contractions], myocarditis, pericardial disease [including both pericardial effusion and pericarditis], vasculitis, and sudden death) corresponding to each case were coded using the Medical Dictionary for Regulatory Activities (MedDRA).
• Association between different CVAEs and BTE was assessed using multivariable logistic regression models with CVAEs as the dependent variable to yield adjusted ROR (aROR).
• Time to onset of CVAEs (vs non-CVAEs) and the time to onset of specific CVAEs was assessed using graphical displays of the empirical cumulative distribution function of each AE.
• Statistical significance was assessed using the Wilcoxon two-sample test.

Results

• A total of 1,437,817 FAERS cases were included in this analysis.
  • Of these, 3668 cases of BTE-related AEs were reported, of which 409 (11.2%) were listed with TECVAYLI as the primary suspected drug.
• Of the 3668 cases, 747 (20.4%) were CVAE related; 65 were reported with TECVAYLI.
• The median age of patients was 52.0 years (IQR, 41.0 years), and 44.4% of BTE recipients were female. Most reports came from the United States (43.2%).

Safety

• The association between CVAEs and TECVAYLI is presented in Table: Association Between CVAEs and the Use of TECVAYLI.

Frequency and associations of CVAEs reported with BTE

• A total of 3668 cases of BTE-related AEs were reported, of which 747 (20.4%) involved a CVAE.
• The median time to onset of CVAEs vs non-CVAEs following BTE therapy was 6 days vs 17 days (P<0.001).
• CVAEs were associated with a significantly higher risk of mortality compared with non-CVAEs (30.1% vs 16.8%; P<0.001).
  • CVAEs were associated with significantly higher mortality rates compared with non-CVAEs (RR, 1.76; 95% CI, 1.54-2.03).
  • The CVAEs with the highest mortality rates were myocarditis (50%), shock (57.7%), heart failure (44.2%), DIC (42.4%), and bleeding (40.9%).
• A total of 16.7% of CVAEs and 18.7% of fatal CVAEs overlapped with CRS, respectively.

Limitations

The limitations to this study were as follows:

• The FAERS database included only reports of BTE-associated AEs from users who experienced them, not all BTE users, which precludes determination of the risk of incident CVAEs.
• The decision to report CVAEs was at the discretion of treating clinicians, potentially introducing reporting bias.
• Users of FAERS might have been incentivized to submit reports of serious AEs, which could inflate the fatality rates of AEs submitted to FAERS.
• Because BTEs have been approved relatively recently, there is a need for more (larger) pharmacovigilance analyses as more data accumulates, especially for newer BTE products, which have limited available data.
• The diagnostic criteria for the reported AEs could not be ascertained, which is particularly important for diagnoses such as myocarditis, where in-depth verification would have been helpful.
• The presence of comorbidities was inferred through the use of medications with a recorded cardiovascular indication, which might’ve underestimated the proportion of cardiovascular comorbidities and the proportion of fatal CVAEs occurring in patients with cardiovascular comorbidities.
• Causality cannot be inferred from the analyses, and confirmation of the causal nature of these signals would require further corroboration by independent sources of data as well as possibly mechanistic insight into BTE-related toxicity.

Stepanovic et al (2023)¹¹ presented results from a single-center, retrospective study that evaluated real-world treatment outcomes in patients with RRMM who received TECVAYLI at Indiana University.

Study Design/Methods

• Patients who received TECVAYLI per standard of care dosing and schedule between October 25, 2022, and July 1, 2023 were included in this study.
• Patients were hospitalized during TECVAYLI step-up dosing.
• Response was assessed after each cycle based on the International Myeloma Working Group (IMWG) Uniform Response Criteria.
• AEs were graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0.

Safety Results

• Within a median follow-up duration of 17.6 weeks, 1 unexplained sudden cardiac death was reported of the 33 patients who received TECVAYLI.

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 10 February 2026.