Summary

• Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• Neurotoxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), has been reported as an adverse event (AE) in the MonumenTAL-1, MonumenTAL-2, TRIMM-2, and RedirecTT-1 studies.^1-5
• MonumenTAL-1 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.^2,5,6
  • Chari et al (2025)^5,7 published the incidence of ICANS from a post hoc analysis of the MonumenTAL-1 study at a median follow-up of 25.6 months (interquartile range [IQR], 8.5-25.9) for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC every other week (Q2W) cohort, and 16.8 months (IQR, 7.6-18.7) for the prior T-cell redirection therapy (TCR)-exposed cohort.
  • Chari et al (2024)⁸ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. ICANS events were reported in the QW, Q2W, and TCR cohorts.
  • Schinke et al (2023)⁶ presented the incidence of neurotoxic events from the MonumenTAL-1 study at a median follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior TCR–exposed cohort.
  • Chari et al (2022)⁹ presented the incidence of neurotoxic events from the phase 1/2 portion of the MonumenTAL-1 study (measured in phase 2 only) at a median follow-up for safety was 11.0 months for the 0.4 mg/kg SC QW cohort and 5.1 months for the 0.8 mg/kg Q2W cohort.
  • Per protocol, neurological toxicities included, but were not restricted to, speech disorders, convulsions, and disturbances in consciousness, confusion, disorientation, or coordination, and ataxia/balance disorders. Neurotoxicity apart from ICANS were managed per institutional guidelines. Dose delays were the primary method for managing neurotoxic AEs in the phase 2 portion of the MonumenTAL-1 study protocol.¹⁰
• MonumenTAL-2 is an ongoing, phase 1b, multi-arm, open-label study evaluating TALVEY in combination with other anticancer therapies in patients with multiple myeloma (MM).^11,12 
  • Cohort E is evaluating the safety and efficacy of TALVEY + pomalidomide in 35 patients with RRMM.¹¹
    • Searle et al (2024)¹² presented the updated the incidence of neurotoxic events of TALVEY + pomalidomide from the MonumenTAL-2 study at a median follow-up of 16.8 months (range, 1.2-25.1).
• RedirecTT-1 is an ongoing, open-label, phase 1b/2 study evaluating the safety and efficacy of TALVEY and TECVAYLI^® (teclistamab-cqyv) in patients with RRMM.^13,14
  • Cohen et al (2025)³ presented the incidence of neurotoxic events in the evaluated cohorts, including in patients with extramedullary disease (EMD) at a median follow-up of 20.3 months for the all-dose levels cohort and 18.2 months (range, 0.7-27.0) for the TALVEY and TECVAYLI recommended phase 2 regimen (RP2R) cohort.
• TRIMM-2 is an ongoing, phase 1b, multicohort open-label study evaluating the efficacy and safety of DARZALEX FASPRO^® (daratumumab hyaluronidase) regimens in combination with TECVAYLI or TALVEY with or without pomalidomide in patients with RRMM.^1,4
  • Bahlis et al (2024)⁴presented the incidence of neurotoxic events in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO + pomalidomide and 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.
  • Dholaria et al (2023)¹ presented the incidence of neurotoxic events 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:
  • Nursing and advance practice practitioner’s considerations for management of ICANS.¹⁵

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.

Clinical Data - Monumental-1 Study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^16,17

The study was conducted in 3 parts; the primary objectives are listed below¹⁰:

• Part 1 (phase 1; dose escalation): to characterize the safety of TALVEY and determine the recommended phase 2 doses (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^6,18:

• TCR naive: 0.4 mg/kg SC QW, not previously exposed to TCR such as chimeric antigen receptor-T cell (CAR-T) therapy or bispecific antibodies (BsAbs; prior B-cell maturation antigen [BCMA] antibody-drug conjugate [ADC] allowed).
• TCR naive: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).
• Prior TCR exposed: 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 type of TCR (CAR-T, BsAb, or CAR-T and BsAb).
• Key eligibility criteria:
  • ≥18 years of age, measurable MM per International Myeloma Working Group (IMWG) criteria.⁵ 
  • ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 monoclonal antibody (mAb).⁵ 
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.⁵ 
• Dosing
  • SUDs of TALVEY were administered as follows⁵:
    • 0.4 mg/kg SC QW: 0.01 mg/kg, and 0.06 mg/kg.
    • 0.8 mg/kg SC Q2W: 0.01 mg/kg, 0.06 mg/kg, and 0.3 mg/kg. 
  • Subsequent treatment doses: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W until disease progression, unacceptable toxic effects, withdrawal of consent, or end of study.⁵  
• Premedications: glucocorticoid (dexamethasone 16 mg or equivalent), antihistamine, and antipyretic were required to be administered for each SUD, and for the first full treatment dose of TALVEY.⁵
• Patients were required to be hospitalized for at least 48 hours from the start of each SUD and the first full treatment dose of TALVEY.⁵

Chari et al (2025)^5,7 published the incidence of ICANS from the post hoc analysis of phases 1 and 2 of the MonumenTAL-1 study at a median follow-up of 25.6 months (IQR, 8.5-25.9) for the 0.4 mg/kg SC QW cohort, 19.4 months (IQR, 9.2-20.7) for the 0.8 mg/kg SC Q2W cohort, and 16.8 months (IQR, 7.6-18.7) for the prior TCR-exposed cohort.

Safety Results

• One patient in the 0.8 mg/kg SC Q2W cohort had grade 2 cerebellar toxicity (reported as ataxia), which led to treatment discontinuation.
• For details regarding ICANS, see Table: MonumenTAL-1 Study: ICANS.

Chari et al (2024)⁸ published the clinical management of AEs in patients with RRMM treated with TALVEY in the MonumenTAL-1 study. Results specific to ICANS are summarized below.

Safety Results

• In MonumenTAL-1, ICANS was graded per American Society for Transplantation and Cellular Therapy (ASTCT) criteria, based on the most severe event experienced, including depressed level of consciousness, seizures, motor findings, raised intracranial pressure, intraocular pressure, or cerebral edema, and immune effector cell-associated encephalopathy (ICE) score.
• Median duration of each ICANS event was 7.8-48.5 hours across the 3 cohorts. See Table: MonumenTAL-1 Study: ICANS Events Associated With TALVEY.
• Most ICANS events were grade 1/2 that occurred with step-up doses (SUDs) and the first full dose. Almost all cases of ICANS events were resolved.
• Two patients each in the 0.4 mg/kg QW and 0.8 mg/kg Q2W cohorts required dose modifications due to ICANS.
• In total, 2 patients in the 0.4 mg/kg QW and 1 patient in the 0.8 kg/mg Q2W cohorts discontinued due to ICANS.

Supportive Measures/Management

• Supportive measures given to patients for managing ICANS in MonumenTAL-1 are detailed in Table: MonumenTAL-1 Study: Most Common Supportive Measures and Concomitant Treatments for ICANS Events.
• Corticosteroids are routinely used for grade ≥2 ICANS events. Corticosteroids have been recommended in the MonumenTAL-1 study as first-line therapy for isolated ICANS, while tocilizumab and corticosteroids have been advised for ICANS events occurring concurrently with CRS.
• Grade 1 ICANS events that are expected to resolve quickly with supportive care should be closely monitored, and other potential causes for symptoms should be excluded through diagnostic tests.
• Severe ICANS cases should be treated in a critical care unit and may require airway protection through intubation and neurology consultation.
• Elevating the head, administering hyperosmolar therapy with mannitol or hypertonic saline, and using hyperventilation along with high-dose corticosteroids are recommended for cerebral edema.
• Levetiracetam is advised for primary seizure prophylaxis in patients with a history of seizures or central nervous system (CNS) disease.
• Experience with TALVEY in MonumenTAL-1 suggests that severe ICANS events are rare and can be effectively managed with appropriate and timely intervention.

Schinke et al (2023)⁶ presented the incidence of neurotoxic events from the MonumenTAL-1 study at a median follow-up of 18.8 months for the 0.4 mg/kg SC QW cohort, 12.7 months for the 0.8 mg/kg SC Q2W cohort, and 14.8 months for the prior TCR–exposed cohort.

Safety Results

• ICANS was reported (measured in phase 2 only) in 10.7% of patients in the 0.4 mg/kg SC QW cohort, 11.0% in the 0.8 mg/kg SC Q2W cohort, and 2.9% in the prior TCR cohort.

Chari et al (2022)⁹ presented the incidence of neurotoxic events from the phase 1/2 portion of the MonumenTAL-1 study (measured in phase 2 only) at a median follow-up for safety was 11.0 months for the 0.4 mg/kg SC QW cohort and 5.1 months for the 0.8 mg/kg Q2W cohort.

Safety Results

• The incidence, timing and duration of ICANS events are summarized in the Table: MonumenTAL-1 Study: ICANS Events.
• ICANS was reported (measured in phase 2 only) in 10-11% of patients across RP2D groups.
  • Most ICANS events were grade 1 or 2
  • Across RP2D groups, 7-8% of patients received supportive measures for ICANS, including tocilizumab and corticosteroids.

MonumenTAL-1 Protocol (Part 3) - Description and Management of Neurotoxic Events¹⁰

• Patients were monitored for neurological toxicities including, but not restricted to, speech disorders, convulsions, and disturbances in consciousness, confusion, disorientation, or coordination, and ataxia/balance disorders.
• A basic neurologic examination including the ICE Assessment Tool was performed at baseline (within 48 hours prior to administration of TALVEY) at SUD-1 and repeated as clinically indicated after the first symptoms of ICANS were suspected until resolution.
• Neurotoxicity that was not assessed as ICANS was managed per institutional guidelines. Patients who experience ICANS grade ≥2 were hospitalized.
• Hospitalization was also required ≥36 hours prior to the initiation of subsequent 2 doses after grade ≥2 ICANS.

MonumenTAL-1 Study Protocol (Part 3) - Dose Modification Guidance¹⁰

• Dose delays were the primary method for managing AEs in part 3 (phase 2) of the MonumenTAL-1 study. If a dose interruption was ≥42 days, treatment must have been permanently discontinued unless continuation was agreed in consultation with the sponsor after a review of safety and efficacy. Repeat of SUDs and pretreatment medication may have been required.
• Ongoing grade 1, 2, or first occurrence of grade 3 ICANS: ICANS must have been completely resolved prior to the next dose.
• For grade ≥1 ataxia, balance disorder, cerebellar symptoms including cerebellar ataxia, cerebellar syndrome, dyskinesia, dysmetria, gait disturbance, intentional tremor, nystagmus and dysarthria, TALVEY must have been withheld, the study team notified and a neurology consult considered. Treatment with TALVEY should have been resumed only after discussion with the medical monitor.
• Following a dose delay, ICANS must have fully resolved before proceeding to the next dose. To proceed to the next dose, there must have been no evidence of serious bacterial, viral, or fungal infection. Any non-hematological toxicity other than CRS or ICANS most have resolved to grade ≤1 or to baseline before proceeding to the next dose with the following exception:
  • Grade ≥1 ataxia, balance disorder, cerebellar symptoms including cerebellar ataxia, cerebellar syndrome, dyskinesia, dysmetria, gait disturbance, intentional tremor, nystagmus and dysarthria; TALVEY treatment could have resumed after discussion with the medical monitor.
• For TALVEY-related toxicities, dose delays were used for management of grade ≥3 clinically significant non-hematologic toxicities (i.e., associated with an AE and/or require intervention).
• Study treatment was discontinued for grade 4 neurotoxicity.
• The following guidelines were to be followed for the management of raised intracranial pressure/cerebral edema:
  • Elevate the head of patient’s bed to an angle of 30 degrees.
  • If patient has ommaya reservoir, drain cerebrospinal fluid (CSF) to target opening pressure of <20 mmHg.
  • Hyperventilation to achieve target PaCO₂ of 28 to 30 mmHg, but maintained for no longer than 24 hours.
  • Consider neurology and/or neurosurgery consultation.
  • Use high-dose corticosteroids with methylprednisolone intravenous (IV) 1 g/day.
  • Hyperosmolar therapy with either mannitol (20 g/dL solution) or hypertonic saline (3% or 23.4%, as detailed below):
    • Mannitol: initial dose 0.5 to 1 g/kg; maintenance at 0.25 to 1 g/kg every 6 hours while monitoring metabolic profile and serum osmolality every 6 hours. Withhold mannitol if serum osmolality is ≥320 mOsm/kg, or the osmolality gap is ≥40.
    • Hypertonic saline: initial 250 mL of 3% hypertonic saline; maintenance at 5075 mL/h while monitoring electrolytes every 4 hours, and withhold infusion if serum sodium levels reach ≥155 mEq/L.
    • For patients with imminent herniation: initial 30 mL of 23.4% hypertonic saline; repeat after 15 minutes, if needed.
  • Consider IV anesthetics for burst-suppression pattern on electroencephalography.

MonumenTAL-1 Study Part 3 - Guidelines for the Management of ICANS¹⁰

MonumenTAL-1 Protocol (Part 3) - Key Prohibited Medications Related to Neurotoxic Events¹⁰

• Corticosteroids in excess of 10 mg daily of prednisone (or equivalent) for more than 14 days were prohibited, other than for the management of AEs where no other treatment options were available and after consultation with the sponsor.

CLINICAL DATA - Monumental-2 study (Cohort e)

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.^11,19

Cohort E of the MonumenTAL-2 study is evaluating the efficacy and safety of TALVEY + pomalidomide in 35 patients with RRMM.^11,19

Study Design/Methods

• Key eligibility criteria:
  • Measurable MM¹¹
  • ≥2 prior lines of treatment including a PI and an immunomodulatory drug¹¹
  • ECOG PS of 0-1¹¹
  • Prior pomalidomide and prior TCR (CAR-T and BsAb) permitted¹¹
  • No prior GPRC5D-targeted therapy¹¹
• Primary endpoint: Safety; AEs were assessed per Common Terminology Criteria for Adverse Events (CTCAE) v5.0, except for CRS and ICANS, which were graded per the ASTCT guidelines.¹¹
• Key secondary endpoints: overall response rate (ORR; assessed per IMWG 2016 criteria), time to response, DOR, and PFS.¹¹

Searle et al (2024)¹² presented the incidence of neurotoxic events 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

• ICANS occurred in 3 patients; all events were grade 1 in severity.

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 efficacy of the combination of TALVEY and TECVAYLI in patients with RRMM.^3,13,14,20

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.^3,14
• Primary endpoints: dose limiting toxicity and ORR.^3,14

Cohen et al (2025)³ published the incidence of neurotoxic events from the phase 1 dose-escalation segment of the RedirecTT-1 study in the all-dose-level cohort at a median follow-up of 20.3 months (range, 0.5-37.1) and in the RP2R cohort at 18.2 months.

Safety Results

• At a data cutoff of March 15, 2024, ICANS events were reported in 3 patients (3%), including 1 grade 3 ICANS event; 1 patient had 2 ICANS events.
• Two out of 4 ICANS events were concurrent with CRS. All ICANS events occurred during SUDs.
• The median time to onset of ICANS was 2.5 days; the median duration of ICANS was 3 days. All events recovered.

CLINICAL DATA - TRIMM-2 STUDY - TALVEY + DArZALEX FASPRO COHORT

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.^1,4,21

Study Design/Methods

• Key eligibility criteria¹:
  • Double refractory to a PI and an immunomodulatory drug or received ≥3 prior lines of treatment (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 endpoints¹:
  • Part 1: identify the RP2D for each treatment combination.
  • Part 2: safety and tolerability at the selected RP2D of each treatment combination.
  • Antitumor activity.
• ICANS was graded per ASTCT criteria.

Bahlis et al (2024)⁴ presented the incidence of neurotoxic events in 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).

Safety Results

• ICANS was reported in 3 patients and all events occurred in the TALVEY 0.8 mg/kg Q2W DARZALEX FASPRO + pomalidomide cohort. One grade 4 ICANS event led to treatment discontinuation.

Dholaria et al (2023)¹ presented the incidence of neurotoxic events 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

• In both the cohorts combined, ICANS was reported in 4.6% of patients, all of which were of grade 1/2 and resolved in 1-2 days.

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 05 May 2025.