SUMMARY

• Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
• Hepatic failure has been reported as an adverse event (AE) leading to death in 1 patient in the MajesTEC-1 study.¹
• Elevated levels of liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], blood alkaline phosphatase [BAP], gamma-glutamyl transferase [GGT], and total bilirubin) with or without concurrent cytokine release syndrome (CRS) have been reported in the MajesTEC-1, MajesTEC-2, and MajesTEC-5 studies.^2,3
• MajesTEC-1 (MMY1001) is a phase 1/2, multicohort study evaluating the safety and efficacy of TECVAYLI in patients with relapsed or refractory multiple myeloma (RRMM).^1,4
  • 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.¹
    • Moreau et al (2022)¹ 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), a total of 68 patients (41.2%) died. Of the 5 deaths the investigators considered TECVAYLI-related, 1 death was due to hepatic failure.
• MajesTEC-2 (MMY1004) 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 Janssen does not recommend the use of TECVAYLI or DARZALEX FASPRO^® (daratumumab and hyaluronidase) in a manner that is inconsistent with the approved labeling.
  • Cohort E included 32 patients with RRMM who received TECVAYLI in combination with DARZALEX FASPRO and lenalidomide (Tec-DR).³
    • Searle et al (2022)³ presented the incidence of hepatotoxic events at a median follow-up of 8.4 months (range, 1.1-12.9). Elevated ALT (any grade) was reported in 28.1% of patients (n=9), with grade 3 or 4 elevations reported in 9.4% of patients (n=3).
• MajesTEC-5 (GMMG-HD10; DSMM-XX; MMY2003) is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY^® (talquetamab-tgvs)-based combination regimens in patients with transplant-eligible newly diagnosed multiple myeloma (TE-NDMM).^5,6 Janssen does not recommend the use of TECVAYLI or TALVEY in a manner that is inconsistent with the approved labeling.
  • Raab et al (2024)⁶ 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 (TECVAYLI Q4W in combination with DARZALEX FASPRO, bortezomib, and lenalidomide; Tec [Q4W]-DVR; n=19) in the MajesTEC-5 study.
    • Any-grade elevated GGT, BAP and ALT treatment-emergent adverse event (TEAEs) were reported in 28.6% (n=14), 16.3% (n=8), and 14.5% (n=7) of patients overall, respectively. Grade 3/4 elevated GGT, BAP, and ALT TEAEs were reported in 12.2% (n=6), 2% (n=1), and 6.1% (n=3) of patients, respectively. Details on hepatotoxic TEAEs in the 3 induction cohorts are provided in Table: MajesTEC- 5 Study: Summary of Hepatotoxic TEAEs.

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

Please refer to the TECVAYLI Prescribing Information for relevant information on the occurrence and management of adverse events.

Warnings and Precautions

• TECVAYLI can cause hepatoxicity, including fatalities.²
• In patients who received TECVAYLI at the recommended dose in the clinical trial, there was one fatal case of hepatic failure.²
• Elevated AST occurred in 34% of patients, with grade 3 or 4 elevations in 1.2%.²
• Elevated ALT occurred in 28% of patients, with grade 3 or 4 elevations in 1.8%.²
• Elevated total bilirubin occurred in 6% of patients with grade 3 or 4 elevations in 0.6%.²
• Liver enzyme elevation can occur with or without concurrent CRS.²
• Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.²

Recommended Dosage Modifications for Other Adverse Reactions

Other Non-Hematologic Adverse Reactions (Based on National Cancer Institute Common Terminology Criteria for Adverse Events [NCI-CTCAE], Version 4.03)

• Grade 3:
  • Withhold TECVAYLI until adverse reaction improves to grade 1 or less.²
• Grade 4:
  • Consider permanent discontinuation of TECVAYLI.²
  • If TECVAYLI is not permanently discontinued, withhold subsequent treatment doses of TECVAYLI (ie, doses administered after TECVAYLI step-up dosing schedule) until adverse reaction improves to grade ≤1.²

Patient Counseling Information

• Advise the patient to read the FDA-approved patient labeling (Medication Guide).²
• Advise patients that liver enzyme elevations may occur and that they should report symptoms that may indicate liver toxicity, including fatigue, anorexia, right upper abdominal discomfort, dark urine, or jaundice.²

clinical data - MAJESTEC-1 STUDY

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

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 of TECVAYLI at the RP2D; Part 3 (the phase 2 component) to evaluate the efficacy of TECVAYLI at the RP2D.^1,4

• Key eligibility criteria for Cohort A (triple-class exposed): measurable MM, RRMM, ≥3 prior lines of therapy (LOTs), prior PI, immunomodulatory drug, and anti-CD38 monoclonal antibody, no prior B-cell maturation antigen (BCMA)-targeted therapy use.¹
  • Per protocol, patients enrolled in the MajesTEC-1 study were required to have adequate hepatic function during the screening phase described as: total bilirubin ≤2.0× upper limit of normal (ULN), except in patients with congenital bilirubinemia, such as Gilbert syndrome (in which case direct bilirubin ≤1.5× ULN was required); AST and ALT ≤3.0× ULN.⁷ 
• Select exclusion criteria:
  • Per study protocol, potential patients who met any of the following criteria were excluded from participation in any part of the MajesTEC-1 study including:
    • Hepatitis B infection or at risk for hepatitis B virus (HBV) reactivation as defined according to the American Society of Clinical Oncology guidelines. Eligibility was determined by the investigator as described in Table: MajesTEC-1 Study Protocol: HBV Screening. In the event the infection status is unclear, quantitative levels were necessary to determine the infection status.⁷ 
    • Active hepatitis C infection as measured by positive hepatitis C virus (HCV)-RNA testing. Patients with a history of HCV antibody positivity underwent HCV-RNA testing.⁷ 

• In patients with negative hepatitis B surface antigen (HBsAg) test, a hepatitis B virus-deoxyribonucleic acid (HBV-DNA) quantification test was required in the following patients to determine eligibility⁷: 
  • Patients who were anti-hepatitis B surface (HBs) antibody positive and without history of vaccination.
  • Patients with positive anti-hepatitis B core (HBc) antibody and either positive or negative anti-HBs. 
  • Patients with known HBV history regardless of anti-HBs/anti-HBc results. 
• For patients with known HBV infection history and negative Hep B serology findings, HBV-DNA was required and must have been negative for inclusion.⁷ 
• Patients with serologic findings suggestive of HBV vaccination (ie, anti-HBs positivity) as the only serologic marker) and a known history of prior HBV vaccination were not required to be tested for HBV-DNA by polymerase chain reaction (PCR).⁷ 
  • Note: Patients with negative HBV-DNA could be enrolled; however, HBV-DNA and AST/ALT laboratories should have been performed every 3 months ±1 month until 6 months post last dose of TECVAYLI.⁷ 
• Primary endpoint: overall response rate (ORR).¹
• Key secondary endpoint for Cohort A: safety.¹

Cohort A

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

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• A total of 165 patients were enrolled in the RP2D cohort; 40 patients were enrolled in phase 1 and 125 patients were enrolled in phase 2.
• Patients received a median of 5 prior LOTs (range, 2-14), 89.7% were refractory to the last LOT, 77.6% were triple-class refractory, and 30.3% were penta-drug refractory.
• At clinical cutoff, 42.4% (n=70) of patients were continuing to receive study treatment; with a median treatment duration of 8.5 months (range, 0.2-24.4).

Safety

• At a median follow-up of 14.1 months, a total of 68 deaths (41.2%) were reported. Of the 5 deaths considered by the investigators to be TECVAYLI-related, one patient died of hepatic failure.

clinical data - Majestec-2 Study

MajesTEC-2 (MMY1004; clinicaltrials.gov identifier: NCT-4722146) 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, no prior BCMA-targeted therapy.³
• Primary endpoints: safety, dose-limiting toxicities, and laboratory abnormalities.³

Cohort E

Searle et al (2022)³ 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).

Results

Treatment Disposition, Baseline Demographics, and Disease Characteristics

• All patients were administered DARZALEX FASPRO and lenalidomide; 19 patients received TECVAYLI 1.5 mg/kg, and 13 patients received TECVAYLI 0.72 mg/kg.
• Patients received a median of 2 LOTs (range, 1-3). All patients were exposed to PI and immunomodulatory drug therapy; 5 patients in each TECVAYLI dose group received prior anti-CD38 antibody therapy.

Safety

• 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-5 study

MajesTEC-5 (GMMG-HD10; DSMM-XX; MMY2003) is an open-label, nonrandomized, phase 2 study assessing the safety and efficacy of TECVAYLI- and TALVEY-based combination regimens in patients with TE-NDMM.^5,6

Study Design/Methods

• Key eligibility criteria: presence of newly diagnosed multiple myeloma (NDMM) for which high-dose therapy (HDT) and autologous stem cell transplant (ASCT) were intended as part of the treatment plan, completion of HDT and ASCT within 12 months of induction start and within 6 months of the last ASCT (7 months if consolidation was received), receipt of only 1 prior LOT, and achievement of at least partial response (PR) as per International Myeloma Working Group (IMWG) 2016 criteria without evidence of progression at the time of enrollment.⁶
• Primary endpoints: safety and tolerability.⁶

Raab et al (2024)⁶ presented the incidence of hepatotoxic events from 3 induction cohorts of the MajesTEC-5 study.

Results

Treatment Disposition

• A total of 49 patients (n=10, arm A; n=20, arm A1; and n=19, arm B) were included in the study.
• Stem cell mobilization was feasible with Tec-DR and Tec-DVR, yielding a median number of 8.4×10⁶/kg CD34-positive cells across the study arms.

Safety

• 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 16 January 2025.