SUMMARY  

• Johnson & Johnson does not recommend the use of TECVAYLI in a manner inconsistent with the approved labeling.
• Additional management recommendations may be available in local/institutional guidelines. Clinicians should use clinical judgement based on local/institutional guidelines, standards of care, and individual patient risk/benefit assessment when considering use of TECVAYLI.
• MajesTEC-3 is a phase 3, randomized, open-label study evaluating the efficacy and safety of TECVAYLI in combination with DARZALEX FASPRO^® (daratumumab and hyaluronidase; 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 relapsed/refractory multiple myeloma (RRMM) after 1-3 prior lines of therapy (LOT).¹ 
  • The MajesTEC-3 study protocol includes prohibited medications, prophylaxis, mitigation, management, and dose interruption strategies related to infections.²

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-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 LOT.¹ 

Study Design/Methods

• Key eligibility criteria: RRMM, 1-3 prior LOT, including a proteasome inhibitor 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 0-2.² 
• Select exclusion criteria related to infections:
  • Active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy.² 
  • Investigational vaccine within 4 weeks.²
  • Received cumulative dose of corticosteroid equivalent to ≥140 mg of prednisone within 14 days before randomization.² 
  • Received a live, attenuated vaccine within 4 weeks before randomization.² 
  • Seropositive for human immunodeficiency virus (HIV).² 
  • Hepatitis B infection (hepatitis B surface antigen [HBsAg], or hepatitis B virus [HBV]-DNA positive). In the event the infection status is unclear, quantitative viral levels are necessary to determine the infection status.² 
  • Active hepatitis C infection by positive hepatitis C virus (HCV)-RNA testing. If a participant with history of chronic hepatitis C infection (defined as both HCV antibody and HCV-RNA positive) completed antiviral therapy and has undetectable HCV-RNA 12 weeks following the completion of therapy, the participant is eligible for the study.² 

MajesTEC-3 Study Protocol – Key Prohibited Medications Related to Infections

• Medications used for other indications that have antimyeloma properties (eg, interferon [IFN] therapy and clarithromycin).² 
  • As an exception, clarithromycin that is prescribed for a course of ≤14 days to treat an infection for which no therapeutic alternative is allowed.
• Systemic corticosteroids should be avoided other than for management of adverse events (AE) and pretreatment medication.² 
  • Systemic corticosteroids administered for the management of AEs is not to exceed a cumulative dose of 140 mg of prednisone or equivalent for 14 days, unless there is no other therapeutic option.
• Cytochrome (CYP) 450 substrates with narrow therapeutic index should be used with caution during a CRS event and from the start of step-up doses (SUD) up to 7 days after the first treatment dose of TECVAYLI is administered.² 
• Patients must not receive a live attenuated vaccine within 4 weeks before randomization, during treatment, and for 30 days after the last dose of TECVAYLI.² 

MajesTEC-3 Study Protocol – Mitigation Strategies Related to the Potential Risk of Infections Associated with TECVAYLI

• Infection Mitigation Strategies: frequent monitoring for the presence of infections, with the acquisition of cultures and/or implementation of empiric antibiotic therapy as appropriate, based on clinical judgment and institutional standards. Perform screening for HBV and HCV, monitor as clinically indicated. Initiate prophylaxis or treatment therapies for infections as appropriate.² 
• HBV Mitigation Strategies: For patients with history of HBV infection, monitor for clinical and laboratory signs of HBV reactivation and for at least 6 months following the end of treatment. Withold study treatment if reactivation is diagnosed and initiate HBV treatment as appropriate.² 
• Progressive multifocal leukoencephalopathy (PML) Mitigation Strategies: monitor for any new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, withhold TECVAYLI and initiate appropriate diagnostic testing. Discontinue TECVAYLI if PML is confirmed.² 
• Hypogammaglobulinemia Mitigation Strategies: Monitor immunoglobulin levels and treat according to local guidelines, including administration of immunoglobulin replacement. Monitor for infection.² 
  • Immune response to vaccines may be reduced.
  • Vaccination with live virus vaccines is not permitted within 4 weeks prior to the start of treatment, during treatment, and for 30 days following the end of treatment.
• Cytopenia Mitigation Strategies: Frequent monitoring of hematologic parameters and provide supportive care according to institutional standards. Prolonged neutropenia may increase the risk of infection.² 

MajesTEC-3 Study Protocol – Infection Prophylaxis

• Prophylactic immunoglobulin replacement should be considered.² 
  • May be initiated prior to first dose of study drug. Alternatively, initiate replacement therapy as early as possible during treatment regardless of immunoglobulin G (IgG) levels and regardless of presence of infections as per institutional or regional guidance.
• Prophylactic administration of antibiotics and antivirals per institutional guidelines.² 
  • May consider initiating broad spectrum antibiotics (eg, levofloxacin) prior to the first dose of study drug and continue for at least 12 weeks.
• Pneumocystis carinii/jirovecci pneumonia prophylaxis.² 
• Prophylaxis for herpes zoster reactivation.² 
  • Initiate antiviral prophylaxis to prevent herpes zoster reactivation within 1 week after the start of administration of study treatment and continue for 3 months following study treatment. Acyclovir, famciclovir, or valacyclovir are acceptable antiviral therapies.

MajesTEC-3 Study Protocol – Infection Management

• For dose interruption parameters related to infection, refer to MajesTEC-3 Study Protocol – Dose Interruption.
• It was recommended that empirical broad-spectrum antibiotics are initiated while performing diagnostic tests in participants with febrile neutropenia or signs/symptoms of infection per institutional guidelines.² 
  • Granulocyte colony-stimulating factor (G-CSF) should be considered for grade 3 neutropenia with infection or fever or any grade 4 neutropenia according to local standards of care. Growth factor support should be avoided during the TECVAYLI SUD period, through the first treatment dose, and during CRS.
• Targeted antimicrobial agents are recommended depending on clinical, radiological and microbiological findings.² 
• For patients with persistent fever with undetermined cause, consider testing for opportunistic infections including new onset or reactivation of viral infections such as herpes viruses (eg, herpes simplex virus, varicella zoster virus, cytomegalovirus, epstein barr virus), parovirus B19, and adenovirus. Diagnostic imaging should be considered as clinically indicated.² 
• PML may be fatal and has been reported in patients receiving TECVAYLI. Patients should be monitored for new onset of or changes in pre-existing neurological signs or symptoms. Withhold treatment with TECVAYLI and initiate appropriate diagnostic testing if PML is suspected. Discontinue TECVAYLI if PML is confirmed.² 
• For a diagnosis of HBV reactivation while on treatment, suspend treatment and any steroids. Utilize current clinical guidelines and consider consulting a hepatitis expert as clinically indicated to manage patients. Resumption of treatment with concomitant antiviral prophylaxis as per standard of care in participants whose HBV reactivation is adequately controlled should be discussed with physicians with expertise in managing HBV and approved by the sponsor.² 

MajesTEC-3 Study Protocol – Management of Hypogammaglobulinemia

The following guidance should have been considered for all patients:

• Prophylactic immunoglobulin replacement should be considered.² 
  • May be initiated prior to first dose of study treatment. Alternatively, initiate replacement therapy as early as possible during treatment regardless of immunoglobulin G (IgG) levels and regardless of the presence of infections as per institutional or regional guidance.
    • Due to potential reactions to intravenous immunoglobulin (IVIG) infusions, it is recommended IVIG be avoided for a minimum of 48 hours after each SUD and also after the first treatment dose of TECVAYLI, as well as during any event of CRS.
• If a patient is not receiving prophylactic IVIG replacement, replacement should start as soon as hypogammaglobulinemia is identified (IgG levels <400 mg/dL) regardless of active or history of infection and replacement should be used to maintain serum IgG levels ≥400 mg/dL. If a participant is hypergammaglobulinemic (IgG levels <400 mg/dL) during screening, IVIG administration should be considered prior to Cycle 1
  Day 1 (C1D1) or as soon as feasible.² 
• Where applicable (IgG heavy chain disease type), assessments to calculate the true IgG level should be considered by subtracting the monoclonal component IgG from the total IgG as a pragmatic approach to determine the underlying non-paraprotein IgG level.² 
• It is recommended to administer immunoglobulin (ie, IVIG 0.4 g/kg every 3 to 6 weeks). After reaching a steady state, IgG levels should be measured at least every 3 months on treatment and for at least 6 months following last dose of study treatment and as clinically indicated.² 

MajesTEC-3 Study Protocol – Vaccinations

• Vaccination is permitted per local guidelines (eg, annual influenza, respiratory syncytial virus, Streptococcus pneumoniae (pneumococcal vaccine), recombinant herpes zoster, and inactivated severe acute respiratory coronavirus 2 (SARS CoV-2) vaccines.² 
• Some types of vaccines (eg, live, attenuated) are not permitted for participants receiving TECVAYLI.² 
• Antibody responses to vaccines may be suboptimal during study treatment and expected adverse reactions to vaccines (eg, fever) and cytokine release syndrome (CRS) may have similar presentation.² 
• Recommended to provide the above vaccinations prior to the first dose of the study drug (as appropriate) and administer vaccinations per schedule while in the treatment phase.² 
• At the discretion of the investigator or institutional practice, it is recommended for patients to receive prophylactic COVID-19 vaccination.² 

MajesTEC-3 Study Protocol – Dose Interruption

Non-Hematologic AEs

• Dosing of TECVAYLI and DARZALEX FASPRO must be interrupted due to non-hematologic AEs such as:²
  • First sign of CRS.
  • First sign of immune effector cell-associated neurotoxicity syndrome (ICANS).
  • Grade ≥3 events that are clinically significant (ie, requiring intervention and/or associated with an AE) except disease-related pain and hypogammaglobulinemia.
  • HBV reactivation.
  • TECVAYLI should be interrupted for grade 1 or 2 infections during SUD through first treatment level dose. Thereafter, TECVALI should be interrupted for any grade 2 infection, unless in the opinion of the investigator and after approval from the sponsor, continued treatment is deemed necessary for disease control.
  • Interruption of DARZALEX FASPRO is per investigator discretion.
• For patients treated with Tec-Dara SC, TECVAYLI must not be administered within 2 hours after resolution of any systemic administration-related reaction related to DARZALEX FASPRO.² 
  • Note that an extended delay between administration of DARZALEX FASPRO and TECVAYLI may require repetition of pretreatment medications.
• Following dose interruption of TECVAYLI or DARZALEX FASPRO, any clinically significant non-hematologic AE other than CRS or ICANS must resolve to grade ≤2 or baseline (as documented in the medical history) before proceeding to the next dose.² 
• Following any dose interruption of TECVAYLI or DARZALEX FASPRO, there must be no evidence of an active bacterial, viral, or fungal infection before proceeding to the next dose of either study treatment.² 

Hematologic AEs

• Dosing of TECVAYLI or DARZALEX FASPRO must be interrupted, and complete blood count (CBC) must be monitored weekly due to neutropenia if any of the following are met.² 
  • Absolute neutrophil count (ANC) <0.5x10⁹/L
  • Febrile neutropenia (fever ≥101.3°F and ANC <1x10⁹/L)
  • ANC <1x10⁹/L and infection of any grade
• Dosing of TECVAYLI or DARZALEX FASPRO may resume once ANC returns to ≥1x10⁹/L.² 
  • TEVAYLI dose reduction or a change in dosing frequency may be considered after consultation with the sponsor.

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 26 February 2026.