SUMMARY

• Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• Oral toxicities and weight loss have been reported as adverse events (AEs) in the MonumenTAL-1, MonumenTAL-2, TRIMM-2, and RedirecTT-1 studies.^1-6
• MonumenTAL-1 (MMY1001) is an ongoing, open-label, phase 1/2 study evaluating the efficacy and safety of TALVEY in patients with relapsed or refractory multiple myeloma (RRMM) after ≥3 prior lines of therapy (LOTs), including a proteasome inhibitor (PI), an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^1,5,7
  • Schinke et al (2024)⁸ presented the incidence of oral and weight loss AEs from a subgroup analysis in Black and White patients at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup. The subgroup of patients received TALVEY at the recommended phase 2 doses (RP2Ds) of 0.4 mg/kg subcutaneous (SC) weekly (QW) and 0.8 mg/kg SC every other week (Q2W).
  • Rasche et al (2024)⁹ presented the incidence of taste-related AEs and taste disorder AEs from the MonumenTAL-1 study at a median follow-up of 29.8 months for the 0.4 mg/kg SC QW cohort, 23.4 months for the 0.8 mg/kg SC Q2W cohort, and 20.5 months for the prior T-cell redirection (TCR) therapy exposed cohort.
  • Chari et al (2024)¹⁰ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. Oral AEs were reported in the QW, Q2W, and TCR cohorts.
  • Jakubiak et al (2023)¹¹presented the incidence of oral AEs and taste disorders AEs in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis, at a median follow-up of 18.4 months for the overall prior TCR cohort, 18.4 months for the prior chimeric antigen receptor modified T-cells (CAR-T) cohort, and 16.3 months for the prior bispecific antibody (BsAb) cohorts.  
  • Chari et al (2023)¹² presented the incidence of oral toxicities and weight loss AEs in patients from the Prospective Dose Intensity Reduction Cohorts of the MonumenTAL-1 study at a median follow-up of 13.2 months.
  • Krishnan et al (2023)¹³ evaluated the incidence of oral AEs in key high-risk and prior B-cell maturation antigen (BCMA) therapy subgroups of patients from the MonumenTAL-1 study.
  • Chari et al (2022)^5,6 published the incidence of oral AEs and decreased weight in the phase 1 portion of the MonumenTAL-1 study. Patients received TALVEY at the first RP2D of 0.405 mg/kg SC QW (median follow-up, 11.7 months), or at the second RP2D of 0.8 mg/kg SC Q2W (median follow-up, 4.2 months).
  • Per MonumenTAL-1 protocol, please see below for management strategies for oral toxicities including dysgeusia, dry mouth and dysphagia.⁷
• MonumenTAL-2 (MMY1004) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with multiple myeloma (MM).^14-17
  • Cohort D is evaluating the efficacy and safety of TALVEY in combination with DARZALEX FASPRO^® (daratumumab hyaluronidase) and lenalidomide in 34 patients with newly diagnosed multiple myeloma (NDMM).
    • Nooka et al (2024)¹⁶ presented the incidence of taste-related treatment-emergent adverse events (TEAEs), dry mouth, and weight loss AEs of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0-14.6) and the TALVEY 0.8 mg/kg every 4 weeks (Q4W) + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).
  • Cohort E is evaluating the safety and efficacy of TALVEY in combination with pomalidomide in patients with RRMM.¹⁷
    • Searle et al (2024)¹⁷ presented the incidence of taste-related AEs, dry mouth, and weight loss AEs of TALVEY + pomalidomide from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).
• RedirecTT-1 (MMY1003) is an ongoing, open-label, phase 1b/2 evaluating the safety and efficacy of TALVEY and TECVAYLI^® (teclistamab-cqyv) in patients with RRMM.^4,18-20
  • Cohen et al (2025)^19,21 published the incidence of oral AEs from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5) cohort.
• TRIMM-2 (MMY1002) is an ongoing, phase 1b, multicohort open-label study evaluating the efficacy and safety of DARZALEX FASPRO in combination with TECVAYLI or TALVEY with or without pomalidomide in patients with RRMM.^3,22,23
  • Bahlis et al (2024)²³ presented the incidence of oral AEs and decreased weight AEs of the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 15.8 months (range, 3.2-37.9) and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort at a median follow-up of 17.5 months (range, 0.2-37.7).
  • Dholaria et al (2023)³ presented the incidence of oral AEs, decreased appetite, and decreased weight AEs from the TALVEY + DARZALEX FASPRO cohorts at a median follow-up of 16.8 months for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO cohort and 15.0 months for the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohort.
• Other relevant literature has been identified in addition to the data summarized above.^2,24-28
  • Health care provider's considerations for management of oral toxicities.^2,27,28 
  • Retrospective descriptive study reported oral toxicities.²⁴ 
  • Prospective observational study quantifying the incidence and severity of dysgeusia and xerostomia.²⁵ 
  • Retrospective descriptive study reported oral toxicities.²⁶ 
  • Patient reported outcomes of oral toxicities.²⁹

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.
• TECVAYLI (teclistamab-cqyv) [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.; https://www.janssenlabels.com/package-insert/product-monograph/prescribing-information/TECVAYLI-pi.pdf.

BACKGROUND

• G protein-coupled receptor, class C, group 5, member D (GPRC5D) is a 7-segment transmembrane orphan receptor protein that belongs to the family of G-protein-coupled receptors.³⁰ It is predominantly expressed in cells with a plasma-cell phenotype, with higher expression levels on the surface of malignant plasma cells in patients with MM, thereby making it a potential immunotherapeutic target.^31-33 It is found to be expressed both as a protein and mRNA in the hard keratinized tissues of the tongue (ie, filiform papillae),^34,35 and residential or interstitial plasma cells within the salivary glands and tonsils.³⁴
• Taste disturbances can be categorized into hypogeusia, ageusia, phantogeusia and dysgeusia. Dysgeusia is commonly used as a general term for any type of taste disorder.³⁶
• Oral toxicities/taste evaluation can be assessed using the following criteria:
  • National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE). Per CTCAE, the maximum possible grade of dysgeusia is 2.³⁷
  • Subjective total taste acuity (STTA).³⁸ 

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^39,40

The study was conducted in 3 parts; the primary objectives are listed below¹:

• Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the RP2Ds and schedule.
• Part 2 (phase 1; dose expansion): to further characterize the safety of TALVEY at the RP2Ds.
• Part 3 (phase 2): to evaluate the efficacy of TALVEY at the RP2Ds.

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts^1,11:

• TCR naïve: 0.4 mg/kg SC QW, not previously exposed to TCR such as Chimeric antigen receptor (CAR)-T therapy or bispecific antibodies (BsAbs; prior BCMA antibody-drug conjugate [ADC] allowed).
• TCR naïve: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).
• Prior TCR: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W, have been previously exposed to TCRs.
  • Among the prior TCR-exposed cohort, patients were divided based on the type of TCR (CAR-T, BsAb or CAR-T and BsAb).
• Key eligibility criteria (Part 3; Phase 2):
  • Measurable MM.¹¹
  • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.¹¹
  • Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2.¹¹
• Key exclusion criteria (Part 3; Phase 2):
  • Prior grade 3 or higher cytokine release syndrome (CRS; per Lee criteria 2014⁴¹) related to any TCR or any prior GPRC5D-targeting therapy.⁷
  • Received cumulative dose of corticosteroids equivalent to ≥140 mg of prednisone within 14 days prior to study drug (not including premedication).⁷
• Primary endpoint: overall response rate (ORR).¹
• Key secondary endpoints: duration of response (DOR), progression-free survival (PFS), overall survival, safety, immunogenicity, and pharmacodynamics.¹

Schinke et al (2024)⁸ presented the incidence of oral-related and weight loss AEs from a subgroup analysis in Black patients who received TALVEY at the RP2Ds of 0.4 mg/kg SC QW and 0.8 mg/kg SC Q2W in phase 1/2 of the MonumenTAL-1 study at a median follow-up of 26 months for the Black subgroup and 31 months for the White subgroup.

Safety Results

• Details on GPRC5D-associated oral-related and weight loss AEs are summarized in Table: MonumenTAL-1 Study: Summary of Oral-Related and Weight Loss AEs in Black vs White Patients and Table: MonumenTAL-1 Study: Characterization of Dysgeusia-Related AEs in Black vs White patients.

Rasche et al (2024)⁹ presented the incidence of oral toxicities and weight loss from the MonumenTAL-1 study in patients receiving TALVEY at a median follow-up of 29.8 months for the 0.4 mg/kg SC QW cohort, 23.4 months for the 0.8 mg/kg SC Q2W cohort, and 20.5 months for the prior TCR cohort.

Safety Results

• Details on GPRC5D-associated oral AEs, including information on dose reductions and discontinuations, are presented in Table: MonumenTAL-1 Study: GPRC5D-Associated Oral AEs.
• Weight loss as assessed by vital signs was reported in 39%, 34%, and 39% of patients in the QW, Q2W, and prior TCR cohorts, respectively.
  • Weight loss occurred early but later stabilized and improved over time, even in patients with oral toxicities. Details are provided in Figure: MonumenTAL-1 Study: Weight Loss in Patients With Oral Toxicity in the QW and Q2W Cohorts.

Chari et al (2024)¹⁰ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. Results specific to oral toxicities and weight loss are summarized below.

Safety Results

• A summary of oral AEs associated with TALVEY in MonumenTAL-1 is presented in Table: MonumenTAL-1 Study: Oral AEs Associated With TALVEY.

Dysgeusia

• Dysgeusia as an AE of any grade was reported in 245 (72%) patients.
  • Some events resolved completely or partially, defined as a reduction in severity from grade 2 to grade 1, while others did not resolve.
  • Dysgeusia can begin shortly after TALVEY dosing, sometimes on the first day or within a few days of step-up dosing.
• The median duration of dysgeusia was 235.5 days (range, 1-870).
• Two patients discontinued due to dysgeusia, both in the 0.8 mg/kg Q2W cohort.

Dry Mouth

• Dry mouth as an AE of any grade was reported in 122 (36%) patients; grade 3/4 events were not observed in any patients.
• The median total duration that patients experienced dry mouth across all events was 216 days (range, 4-628).
• No patients discontinued treatment due to dry mouth.

Dysphagia

• Dysphagia as an AE of any grade was reported in 82 (24%) patients, and grade 3/4 events were observed in 3 (1%) patients.
  • Most dysphagia cases were low grade.
  • Three (2.1%) patients, all in the 0.8 mg/kg Q2W cohort, had grade 3 dysphagia.
• The median duration of dysphagia was 165.5 days (range, 20-572).
• No patients discontinued treatment due to dysphagia.

Supportive Measures/Management

• The MonumenTAL-1 protocol specified that oral events should be managed with mouth rinses, such as salt water or liquid corticosteroids, pain medications, and short courses of oral corticosteroids.
• Per investigator experience, dose modification was the most effective management strategy for dysphagia, dysgeusia and dry mouth as per the investigator’s experience. See Table: MonumenTAL-1 Study: Dose Modifications for Oral Events for additional details.
• Concomitant medications were also used to manage dysphagia, dysgeusia and dry mouth in all 3 cohorts. The efficacy of these measures were not formally assessed. See Table: MonumenTAL-1 Study: Most Common Supportive Measures and Concomitant Treatments for Oral AEs for additional details.

Dysgeusia

• Increased TALVEY exposure led to a higher incidence of dysgeusia.
• Nutritional monitoring and appropriate supplementation were implemented.
• High caloric shakes were advised to ensure adequate nutritional intake and prevent weight loss.
• Increased TALVEY exposure led to a higher incidence of dysgeusia.
• Patients experiencing weight loss may need adjustments to weight-based medications, including TALVEY, and other conditions like hypotension and diabetes mellitus should be monitored closely.

Dry mouth

• Increased hydration, intraoral topical agents, and sodium lauryl sulfate-free toothpastes were suggested by investigators to manage dry mouth.

Dysphagia

• Tramadol and oxycodone were used for pain, while corticosteroids were used to control inflammation.
• “Magic mouthwash” containing at least 3 of an antihistamine, anesthetic, antacid, antifungal, corticosteroid, or antibiotic was used to manage pain and inflammation.
• Frequent liquids and artificial saliva were administered for dry mouth-induced dysphagia.

Jakubowiak et al (2023)¹¹ presented the incidence of oral toxicities in patients with prior TCR, including an additional 19 patients enrolled in the MonumenTAL-1 study since the prior analysis, at a median follow-up of 18.4 months for the overall prior TCR cohort and the prior CAR-T cohort and 16.3 months for the prior BsAb cohort.

Safety Results

• Oral-related AEs are summarized in Table: MonumenTAL-1 Study: Oral-Related AEs (Prior TCR).

Chari et al (2023)¹² presented the incidence of oral toxicities and weight loss AEs of patients in MonumenTAL-1 who switched to reduced or less frequent dosing with TALVEY at a median follow-up of 13.2 months.

Study Design/Methods

• Patients were divided into Responsive Dose Intensity Reduction Cohorts and Prospective Dose Intensity Reduction Cohorts.
  • Prospective Dose Intensity Reduction Cohorts (n=19):
    • TALVEY 0.8 mg/kg Q2W was reduced to 0.4 mg/kg Q2W in 9 patients who had at least partial response (≥PR).
    • TALVEY 0.8 mg/kg Q2W was reduced to 0.8 mg/kg once Q4W in 10 patients who had ≥PR.

Safety Results

• At the data cutoff of October 2, 2023, prospective cohorts showed a trend toward improved resolution of oral toxicities after switch. The same trend was not seen with weight loss. Resolution of oral toxicity and weight loss after switching to less frequent or lower intensity dosing of TALVEY are presented in Figure: MonumenTAL-1 Study: Prospective Cohorts With Change in Oral Toxicity and Weight Loss After Switch vs Matched Cohort Without Dose Reduction.

Krishnan et al (2023)¹³ evaluated the incidence of oral-related AEs of TALVEY in key high-risk and prior BCMA therapy subgroups of patients from the phase 1/2 MonumenTAL-1 study.

Safety Results

• Oral-related AEs observed in the high-risk patient subgroups are summarized in Table: MonumenTAL-1 Study: Summary of Oral-related AEs in High-risk Subgroups.
• Oral-related AEs observed in the prior BCMA therapies subgroups are summarized in Table: MonumenTAL-1 Study: Summary of Oral-Related AEs in Prior BCMA Subgroups.

Chari et al (2022)⁵ published the incidence of oral toxicities and weight loss AEs from the phase 1 portion of the MonumenTAL-1 study at a median follow-up of 11.7 months (range, 1.0-21.2) for the 0.405 mg/kg SC QW cohort and 4.2 months (range, 0.7-13.7) for the 0.8 mg/kg SC Q2W cohort.

Study Design/Methods

• Patients received TALVEY at a dose of 0.0005-0.18 mg/kg intravenous (IV) QW or Q2W, at the first RP2D of 0.405 mg/kg SC QW, or at the second RP2D of 0.8 mg/kg SC Q2W.
• Additional IV and SC doses were evaluated in order to determine the RP2Ds.

Safety Results

• AEs related to oral toxicities and weight loss are summarized in the Table: MonumenTAL-1 (Phase 1) Study: Oral-Related and Weight Loss AEs.
• The median time to onset of dysgeusia (relative to the first TALVEY dose) was 13.5 days (range, 1-350) and the median duration was 47.5 days (range, 4-382).⁶

MonumenTAL-1 Study Protocol (Part 3) - Description and Management of Oral Toxicities⁷

• Oral toxicity can manifest as dysgeusia, dry mouth, and dysphagia.
• Oral toxicities are often low grade, and weight loss can occur over time.
• Initial workup may include evaluation for active infections (eg, herpes simplex virus [HSV], thrush) with appropriate treatment.
• Symptomatic management can include mouth rinses (salt water, steroid liquid formulations), nutrition consult, pain management as indicated, and possibly a short course of oral steroids in consultation with sponsor.
• Refractory symptoms may require further evaluation by an ear, nose and throat, or gastrointestinal specialist.

CLINICAL DATA - Monumental-2 study

MonumenTAL-2 (MMY1004; clinicaltrials.gov identifier NCT05050097) is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with MM.^14-17

Study Design/Methods

• Key eligibility criteria:
  • Cohort D: measurable MM, NDMM, ECOG PS of 0-1, and transplant ineligible or not intended for transplant.^15,16
  • Cohort E: measurable MM, ≥2 prior LOTs, including a PI and an immunomodulatory drug, ECOG PS of 0-1, prior pomalidomide and prior TCR (CAR-T and BsAb) permitted, and no prior GPRC5D-targeted therapy.^15,17
• Primary endpoint for Cohort D and Cohort E: safety; AEs assessed per CTCAE v5.0, except for CRS and immune effector cell-associated neurotoxicity syndrome, which were graded per American Society for Transplantation and Cellular Therapy (ASTCT) guidelines.^15-17

Cohort D

Nooka et al (2024)¹⁶ presented the incidence of oral toxicities and weight loss AEs of the TALVEY 0.6 mg/kg Q2W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 13.2 months (range, 10.0-14.6) and the TALVEY 0.8 mg/kg Q4W + DARZALEX FASPRO + lenalidomide cohort at a median follow-up of 5.8 months (range, 1.7 [denotes patients who died]-12.0).

Safety Results

• Oral toxicities and weight loss related TEAEs are summarized in Table: MonumenTAL-2 Study (Cohort D): Summary of Oral Toxicities and Weight Loss TEAEs.
• No treatment discontinuations were reported due to oral toxicities or weight loss TEAEs.

Searle et al (2024)¹⁷ presented the incidence of oral toxicities and weight loss AEs in the TALVEY + pomalidomide cohort from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).

Safety Results

• Oral toxicity and weight loss reported at a data cutoff date of April 22, 2024, are summarized in Table: MonumenTAL-2 (Cohort E) Study: Summary of Oral Toxicity and Weight Loss.
• In patients with or without oral toxicities, weight loss was evident early but stabilized and improved over time, with a gradual improvement noted in patients with oral toxicities.

CLINICAL DATA - redirectt-1 STUDY - tAlvey + tecvayli COHORT

RedirecTT-1 (MMY1003; clinicaltrials.gov identifier: NCT04586426) is an ongoing, open-label, phase 1b/2 study evaluating the safety and effectiveness of the combination of TALVEY and TECVAYLI in patients with RRMM.^4,18-20

Study Design/Methods

• Key inclusion criteria: relapsed or refractory or intolerant to established therapies including the last LOT; prior exposure to a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.^19,20
• Primary endpoints: dose limiting toxicity and ORR.^19,20

Cohen et al (2025)^19,21 published the incidence of oral AEs from the phase 1 dose-escalation segment of the RedirecTT-1 study at a median follow-up of 20.3 months (range, 0.5-37.1) in the all dose levels (dose levels 1-5) and 18.2 months in the recommended phase 2 regimen (RP2R; dose level 5) cohorts.

Safety Results

• At a data cutoff of March 15, 2024, the incidence of oral AEs is presented in the Table: RedirecTT-1 Study: Oral-Related AEs.
• GPRC5D-related taste-change AEs are detailed in Table: RedirecTT-1 Study: Summary of GPRC5D-Related Taste-Change AEs in Patients Across All Dose Levels

CLINICAL DATA - TRIMM-2 STUDY

TRIMM-2 (MMY1002; clinicaltrials.gov identifier: NCT04108195) is an ongoing, phase 1b, 2-part, multicohort, open-label study evaluating DARZALEX FASPRO regimens in combination with bispecific TCR antibodies with or without pomalidomide in patients with RRMM.^3,22,23

Study Design/Methods

• Key eligibility criteria³:
  • Double refractory to a PI and an immunomodulatory drug or received ≥3 prior LOTs (including a PI and an immunomodulatory drug).
  • Treatment with an anti-CD38 monoclonal antibody (>90 days prior allowed) including anti-CD38 refractory patients.
  • Prior BsAb and CAR-T were allowed.
• Key primary endpoints³:
  • Part 1: identify the RP2D for each treatment combination.
  • Part 2: safety and tolerability at the selected RP2D of each treatment combination.
  • Antitumor activity.

Bahlis et al (2024)²³ presented the incidence of oral toxicities and weight loss AEs the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohorts at a median follow-up of 15.8 months (range, 3.2-37.9) and 17.5 months (range, 0.2-37.7), respectively.

Safety Results

• AEs related to oral toxicities and weight loss are summarized in the Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO + Pomalidomide Cohort): Oral-Related and Weight Loss AEs.
• No treatment discontinuations were reported due to taste AEs.

Dholaria et al (2023)³ presented the incidence of oral toxicities and weight loss AEs in the TRIMM-2 study for the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO 1800 mg Q4W cohort at a median follow- up of 16.8 months (range, 1.9-31.0) and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO 1800 mg Q4W cohort at a median follow-up of 15.0 months (range, 1.0-23.3).

Safety Results

• AEs related to oral toxicities and weight loss are summarized in the Table: TRIMM-2 Study: Oral-Related and Weight Loss AEs.
• Dysgeusia was reported in 76.9% of patients, 6.2% required TALVEY dose reduction.
• Dysgeusia and dry mouth were managed with mouth washes, saliva stimulants, or dose modifications.

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 27 February 2025.