TALVEY - Management of Infections and Hypogammablobulinemia in the MonumenTAL-3 Study

SUMMARY

• Johnson & Johnson does not recommend the use of TALVEY in a manner that is 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.
• Please refer to local labeling for neurotoxicity management recommendations.
• Consider further management per current practice guidelines or institutional guidelines.
• MonumenTAL-3 is a phase 3 randomized, open-label, multicenter study comparing the efficacy and safety of TALVEY in combination with DARZALEX FASPRO^® (daratumumab hyaluronidase) and pomalidomide (Tal-DP) or TALVEY in combination with DARZALEX FASPRO (Tal-D) or DARZALEX FASPRO in combination with pomalidomide and dexamethasone (DPd) in patients with relapsed/refractory multiple myeloma (RRMM) who have received ≥1 line of therapy (LOT).¹
  • The MonumenTAL-3 study protocol included permitted therapies, prohibited medications, mitigation strategies, prophylaxis, HBV reactivation, and dose delay.

PRODUCT LABELING

• TALVEY (talquetamab-tgvs) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TALVEY-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 – MonumenTAL-3 STUDY

MonumenTAL-3 (NCT05455320) is a phase 3 randomized, open-label, multicenter study comparing the efficacy of Tal-D or Tal-DP vs DPd in patients with RRMM who have received ≥1 prior LOT.¹

Study Design/Methods

• Patients (N=864) underwent 1:1:1 randomization to Tal-DP (n=287), Tal-D (n=287), or DPd (n=290) treatment arms.¹
• Key eligibility criteria¹: ≥18 years of age with measurable RRMM; ≥1 prior LOT, including lenalidomide and a proteasome inhibitor (PI); Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0-2.¹
• Select exclusion criteria related to infections²:
  • Patients who received:
    • An investigational vaccine, other than a severe acute respiratory syndrome coronavirus 2 (SARSCoV2) vaccine authorized for emergency use, within 4 weeks.
    • A live, attenuated vaccine within 4 weeks.
    • A cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days before the first dose of study drug.
  • 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.
  • Active hepatitis C virus (HCV) infection defined by positive HCV-RNA test. Participants with a history of HCV antibody positivity must undergo HCV-RNA testing. Participants with a history of chronic hepatitis C infection (defined by positive HCV antibody and HCV-RNA tests) are eligible if they have completed antiviral therapy and maintained undetectable HCV-RNA levels for at least 12 weeks after completion of treatment.
  • Concurrent medical or psychiatric condition or disease that is likely to interfere with study procedures or outcomes, or that, in the investigator's judgment, may pose a risk to study participation, including:
    • Evidence of active systemic viral, fungal, or bacterial infection, requiring systemic antimicrobial therapy.

MonumenTAL-3 Study Protocol - Key Permitted Therapies Related to Infections and Hypogammaglobulinemia

• Standard supportive care therapies may be administered as clinically indicated, in accordance with institutional guidelines and at the investigator’s discretion. These may include antibiotics and other antimicrobial agents.²
• Immunoglobulin replacement therapy (intravenous [IV]/subcutaneous immunoglobulin [SCIG]) should be administered to patients with hypogammaglobulinemia (immunoglobulin G [IgG]<400 mg/dL) as per European Myeloma Network (EMN) recommendations.²
  • Due to the potential risk of reactions, administration should be avoided for at least 48 hours following each step-up dose and after the first treatment dose of TALVEY, as well as during any cytokine release syndrome (CRS) event.²
• Documented infectious complications should be managed with oral or IV antibiotics, or other anti-infective agents, as appropriate for the specific infection and in accordance with institutional guidelines and the treating investigator’s judgment.
• Corticosteroids used as pretreatment medication are permitted.²
• Vaccination is permitted in accordance with local guidelines, including annual influenza vaccines and inactivated SARSCoV2 vaccines approved or authorized for emergency use. However, certain vaccines, such as live, attenuated vaccines, are not allowed. Participants should be advised that antibody responses to vaccination may be suboptimal during study treatment.²

MonumenTAL-3 Study Protocol - Key Prohibited Medications Related to Infections

• Vaccination with a live, attenuated vaccine is not permitted during treatment and for 30 days after the last dose of study treatment unless prior discussion with the sponsor. Annual influenza and SARS-CoV-2 vaccines approved or authorized for emergency use are permitted. The sponsor should be consulted before administering any other inactivated vaccines. Patients should be advised that vaccine-induced antibody responses may be suboptimal during the study.²
  • Prohibited and restricted therapies specific to TALVEY: For inactivated vaccines, initial vaccination or booster doses should not coincide with step-up dosing or the cycle 1 day 1 treatment dose, when the risk of CRS is highest. In addition, administration of a vaccine or booster on the same day as any treatment dose after cycle 1 day 1 is not recommended.
• Medications used for indications other than multiple myeloma that possess antimyeloma properties (eg, interferon and clarithromycin).²
  • Exception: Clarithromycin prescribed for a treatment course of ≤14 days to manage an infection for which no therapeutic alternative is available is permitted.
• Systemic corticosteroids should be avoided except when used for the management of adverse events (AEs) or as pretreatment medication.²
  • Corticosteroids may be administered for AE management when no alternative therapeutic option is available; however, the dosing regimen must not exceed a cumulative dose of 140 mg prednisone (or equivalent) over 14 days.
• CYP450 substrates with narrow therapeutic index should be used with caution during a CRS event and for 48 hours after administration of step-up doses and the first treatment dose of TALVEY.²

MonumenTAL-3 Study Protocol - Mitigation Strategies Related to Infections and Hypogammaglobulinemia Associated with TALVEY

• Closely monitor for signs and symptoms of infection, including obtaining cultures and initiating empiric antibiotic therapy when appropriate, based on clinical judgment and institutional practice. Screen for HBV and HCV infection and continue monitoring as clinically warranted. Implement infection prophylaxis or treatment as appropriate.²
• Assess immunoglobulin levels during and after treatment and manage according to local guidelines, including the use of immunoglobulin replacement therapy when indicated. Monitor for infections.²

MonumenTAL-3 Study Protocol - Infection Prophylaxis

• Due to the increased susceptibility of patients with multiple myeloma to infections, prophylactic antibiotics are recommended as per institutional guidelines, and it includes the following²:
  • Immunoglobulin replacement therapy (IV/SCIG) should be administered to patients with hypogammaglobulinemia (IgG<400 mg/dL) as per EMN recommendations.
  • Prophylaxis against Pneumocystis carinii/jirovecii pneumonia.
  • Measures to prevent herpes zoster reactivation:
    • Antiviral prophylaxis should be initiated within 1 week after starting study treatment and continued for 3 months after completion of treatment.
    • Acceptable antiviral agents include acyclovir (eg, 400 mg orally 3 times daily or 800 mg orally twice daily), famciclovir (eg, 125 mg orally twice daily), or valacyclovir (eg, 500 mg orally twice daily).

MonumenTAL-3 Study Protocol - HBV Reactivation

• HBV reactivation is considered a potential risk associated with study treatment across all 3 arms.²
• Primary antiviral prophylaxis is permitted as per local standard of care.
  HBV-DNA testing using polymerase chain reaction (PCR) is required for participants at risk of HBV reactivation.²
• If HBV reactivation is diagnosed during treatment (ie, HBV-DNA becomes detectable), TALVEY and any corticosteroids should be interrupted, and appropriate management should be initiated.²
• Resumption of TALVEY in participants with adequately controlled HBV reactivation should be discussed with physicians experienced in HBV management and approved by the sponsor.²

MonumenTAL-3 Study Protocol - Dose Delay Considerations Related to Infections

• Dosing of TALVEY and DARZALEX FASPRO must be delayed due to nonhematologic toxicities, such as HBV reactivation.²
• Following any dose delay of TALVEY or DARZALEX FASPRO, there must be no evidence of a serious bacterial, viral, or fungal infection before proceeding to the next dose of TALVEY or DARZALEX FASPRO.²

Literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File (and/or other resources, including internal/external databases) was conducted on 16 July 2026.