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TALVEY® (talquetamab-tgvs)
Medical Information
TALVEY - Occurrence and Management of Neurotoxicity Including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
Last Updated: 02/17/2026
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-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 (mAb).
1 - Chari et al (2025)1 published the incidence of ICANS from a post hoc analysis of the MonumenTAL-1 study at a median follow-up of 25.6 months for the 0.4 mg/kg subcutaneous (SC) weekly (QW) cohort, 19.4 months for the 0.8 mg/kg SC every other week (Q2W) cohort, and 16.8 months for the prior T-cell redirection therapy (TCR)-exposed cohort.
- Chari et al (2022)2
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.
- 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).3
- 5 - Cohort E is evaluating the safety and efficacy of TALVEY + pomalidomide in 35 patients with RRMM.3,
5 - Quach et al (2025)3 presented the incidence of neurotoxic events from the TALVEY + pomalidomide cohort of the MonumenTAL-2 study at a longer median follow-up of 20.7 months.
- Searle et al (2024)5 presented the updated the incidence of neurotoxic events from the TALVEY + pomalidomide cohort of the MonumenTAL-2 study at a median follow-up of 16.8 months.
- Cohort E is evaluating the safety and efficacy of TALVEY + pomalidomide in 35 patients with RRMM.3,
- 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 , including those with extramedullary disease (EMD).6 ,7 - Kumar et al (2025)7 published the incidence of neurotoxic events from phase 2 of the RedirecTT-1 study in patients with RRMM and EMD at a median follow-up of 12.6 months.
- Cohen et al (2025)6 presented the incidence of neurotoxic events in the evaluated cohorts, including in patients with EMD at a median follow-up of 20.3 months for the all-dose levels cohort and 18.2 months 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.8
-10 - Chari et al (2025)10 published the incidence of neurotoxic events in the TALVEY 0.4 mg/kg QW + DARZALEX FASPRO and the TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO cohorts at a median follow-up of 18.6 months (range, 1.2-39.1).
- Bahlis et al (2024)9
presented 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 and 17.5 months, respectively.
TRIMM-3 is a phase 1b, nonrandomized, open-label study evaluating the dosing, safety, and tolerability of a programmed cell death receptor-1 (PD-1) inhibitor in combination with TALVEY or TECVAYLI in patients with RRMM.11 ,12 - Perrot et al (2025)11 presented the incidence of neurotoxic events of the TALVEY + cetrelimab cohort at a median follow-up of 11.5 months.
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
Patients were enrolled into 1 of the following 4 cohorts:
- 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).15
,16 - TCR naive: 0.8 mg/kg SC Q2W, not previously exposed to TCRs (prior BCMA ADC allowed).15,16
- TCR exposed: 0.4 mg/kg SC QW or 0.8 mg/kg SC Q2W, have been previously exposed to TCRs.15,16
- Key eligibility criteria1:
- ≥18 years of age, measurable MM per International Myeloma Working Group (IMWG) criteria.
- ≥3 prior LOTs including a PI, an immunomodulatory drug, and an anti-CD38 mAb.
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0-2.
- 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.
| Event | 0.4 mg/kg SC QWa,b (N=122) | 0.8 mg/kg SC Q2Wa,b (N=118) | Prior TCRa,b (N=61) |
|---|---|---|---|
| Patients with ICANS, n (%) | 13 (11) | 12 (10) | 2 (3) |
| Grade 1 | 4 (3) | 4 (3) | 2 (3) |
| Grade 2 | 7 (6) | 4 (3) | 0 |
| Grade 3 | 2 (2) | 3 (3) | 0 |
| Grade 4 | 0 | 1 (1) | 0 |
| ICANS symptoms (≥2% in any cohort), n (%) | |||
| Confusional state | 6 (5) | 5 (4) | 0 |
| Disorientation | 3 (2) | 2 (2) | 0 |
| Somnolence | 3 (2) | 2 (2) | 0 |
| Depressed level of consciousness | 3 (2) | 1 (1) | 0 |
| Median time to onset, hours (IQR)c | 23.6 (15.0-53.7) | 31.9 (14.7-52.0) | 81.6 (47.6-115.5) |
| Median duration, hours (IQR) | 15.5 (2.7-23.9) | 7.8 (3.5-24.9) | 25.3 (2.0-48.5) |
| Number of ICANS events, n (%) | 21 (-) | 15 (-) | 2 (-) |
| Recovered or resolved | 18 (86) | 12 (80) | 2 (100) |
| Not recovered or not resolved | 2 (10) | 2 (13) | 0 |
| Recovering or resolving | 1 (5) | 0 | 0 |
| Unknown | 0 | 1 (7) | 0 |
| Concurrent CRS, n (%)d | |||
| Yes | 14 (67) | 10 (67) | 2 (100) |
| No | 7 (33) | 5 (33) | 0 |
| Treatment discontinuation due to ICANS, n (%) | 2 (2)e | 1 (1)e | 0 |
| Dose reduction due to ICANS, n (%) | 1 (1)e | 0 | 0 |
| Abbreviations: CRS, cytokine release syndrome; ICANS, immune effector cell-associated neurotoxicity syndrome; IQR, interquartile range; Q2W, every other week; QW, weekly; SC, subcutaneous; SUD, step-up dose; TCR, T-cell redirection therapy. Clinical data cutoff date of October 11, 2023. a b cRelative to the most recent dose. dConcurrent CRS includes ICANS events that occur simultaneously with CRS or within 7 days after its resolution.eAssessed only in phase 2, with percentage calculated based on n=122 for the 0.4 mg/kg SC QW cohort and n=118 for the 0.8 mg/kg SC 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.
| Parameter, n (%) | 0.4 mg/kg SC QWa (n=122)b | 0.8 mg/kg SC Q2Wa (n=109)b |
|---|---|---|
| Patients with ICANS | 13 (10.7) | 11 (10.1) |
| Maximum ICANS Grade | ||
| Grade 1 | 4 (3.3) | 3 (2.8) |
| Grade 2 | 7 (5.7) | 6 (5.5) |
| Grade 3 | 2 (1.6) | 2 (1.8) |
| Median time to onsetc, days (range) | 2.0 (1-9) | 3.0 (2-16) |
| Median duration, days (range) | 2 (1-22) | 1 (1-15) |
| Outcome of ICANS | ||
| Number of ICANS eventsd | 21 | 14 |
| Recovered/resolved | 18 (85.7) | 11 (78.6) |
| Not recovered/not resolved | 2 (9.5) | 2 (14.3) |
| Fatal | 0 | 0 |
| Patients with concurrent CRSe | ||
| Yes | 14 (66.7) | 8 (57.1) |
| No | 7 (33.3) | 6 (42.9) |
| Abbreviations: CRS, cytokine release syndrome; CTCAE, Common Terminology Criteria for Adverse Events; ICANS, immune effector cell-associated neurotoxicity syndrome; QW, every week; Q2W, every other week; SC, subcutaneous; SUD, step-up dose. Clinical data cutoff date of May 16, 2022. These AEs were assessed per CTCAE v4.03. aWith 2–3 SUDs. bICANS was only measured in phase 2. cRelative to the most recent dose. dOne ICANS event outcome was recovering or resolving in the 0.4 mg/kg SC QW cohort, and one ICANS event had an unknown outcome in the 0.8 mg/kg SC Q2W cohort. eConcurrent CRS considers ICANS events that occur during or within 7 days of the end date of CRS. | ||
- In MonumenTAL-1 (N=339), ataxia/balance disorder occurred in 4.1% of patients (N=14).
- Ataxia/balance disorder events were grade 1 (1.5%), grade 2 (2.4%), and grade 3 (0.3%). No grade 4 or 5 events occurred.
- The most frequent clinical manifestation of ataxia/balance disorder events reported were dysarthria (1.5%), gait disturbance (1.5%), and balance disorder (0.9%), and 0.9% of patients experienced more than one ataxia/balance disorder event.
- The median time to onset was 77 days (range, 2-463) from the first dose and 4 days (range, 1-13) from the last dose, and 7 (38.9%) of the 18 events did not resolve.
Study Design/Methods
- Key eligibility criteria:
- 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.3
Safety Results
- No new ICANS events were reported in the TALVEY + pomalidomide cohort since the last data cutoff.
Safety Results
- ICANS occurred in 3 patients; all events were grade 1 in severity.
CLINICAL DATA - REDIRECTT-1 STUDY - TALVEY + tecvayli COHORT
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 mAb.6
Safety Results
- At the data cutoff date of March 18, 2025, ICANS was reported in patients with RRMM and EMD (N=90).
- Any-grade ICANS was reported in 12.2% of patients (n=11); grade 1 ICANS was reported in 5.6% of patients (n=5); grade 2 in 4.4% (n=4); grade 3 in in 1.1% (n=1) and grade 4 in 1.1% (n=1).
- ICANS was reported in 2.2% of patients (n=2) during SUD 1, 4.4% of patients (n=4) during SUD 2, 7.8% of patients (n=7) during SUD 3, and 2.2% of patients (n=2) during cycle 1; no events occurred from cycle 2 onwards.
- Median time to onset was 3 days (range, 1-7) relative to the most recent dose, based on 15 ICANS event.
- Median duration of ICANS events was 2 days (range, 1-7), based on 14 ICANS events.
- Among patients with ICANS, 91% (n=10) received supportive measures, including corticosteroids in 10.0% (n=9), levetiracetam in 4.4% (n=4), anakinra in 2.2% (n=2), other measures in 2.2% (n=2), and tocilizumab in 1.1% (n=1); patients could have received >1 supportive therapy.
- Treatment discontinuation due to grade 4 ICANS was reported in 1 patient and deemed related to TALVEY or TECAVYLI by the investigator.
A recovered or resolved outcome was reported in 93.3% of patients (n=14), whereas a not recovered or resolved outcome was reported in 6.7% of patients (n=1; patient also had unresolved CRS), based on 15 ICANS events.
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
Study Design/Methods
- Key eligibility criteria10:
- 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 mAb (>90 days prior allowed) including anti-CD38 refractory patients.
- Prior BsAb and CAR-T were allowed.
- ICANS was graded per American Society for Transplantation and Cellular Therapy (ASTCT) criteria.
Safety Results
- Neurotoxicity was reported in 34% of patients (n=22), with one grade 3 event (syncope, lasting 1 day) reported. See Table: TRIMM-2 Study (TALVEY + DARZALEX FASPRO Cohort): Neurotoxicity.
- ICANS was reported in 5% of patients (n=3); all events were grade 1/2 and resolved within 1-2 days, with no dose reductions reported.
- Discontinuation of TALVEY and DARZALEX FASPRO due to cerebellar syndrome was reported in 2% of patients (n=1).
- Discontinuation of DARZALEX FASPRO due to peripheral sensory neuropathy was reported in 2% of patients (n=1).
- Dose-reduction of TALVEY and DARZALEX FASPRO due to headache was reported in 2% of patients (n=1).
| Neurotoxicity eventsa | TALVEY 0.4 mg/kg QW + DARZALEX FASPRO (n=14) | TALVEY 0.8 mg/kg Q2W + DARZALEX FASPRO (n=51) |
|---|---|---|
| Patients with neurotoxicity, n (%) | 5 (36) | 17 (33) |
| Grade 1 | 2 (14) | 8 (16) |
| Grade 2 | 3 (21) | 8 (16) |
| Grade 3 | 0 | 1 (2) |
| Leading to discontinuation, n (%) | 0 | 1 (2) |
| Median time to onsetb, days (range) | 2 (1-8) | 3 (1-29) |
| Median duration, days (range) | 12.5 (2-371) | 9 (1-387) |
| Outcome, n | 9 | 38 |
| Recovered or resolved, n (%) | 6 (67) | 24 (63) |
| Not recovered or not resolved, n (%) | 3 (33) | 13 (34) |
| Recovering or resolving, n (%) | 0 | 1 (3) |
| Abbreviations: ASTCT, American Society for Transplantation and Cellular Therapy; ICANS, immune effector cell-associated neurotoxicity syndrome; Q2W, every other week; QW, weekly. aICANS graded according to the ASTCT criteria. Nervous system disorders include allodynia, anosmia, cerebellar syndrome, dizziness, dysarthria, headache, ICANS, neuromyopathy, paresthesia, peripheral motor neuropathy, peripheral sensory neuropathy, presyncope, syncope, and tremor. Psychiatric disorders include insomnia. bRelative to most recent dose. Data cutoff date: November 17, 2023. | ||
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.
Study Design/Methods
- Key eligibility criteria11:
- MM per IMWG criteria
- RRMM who may not be eligible for or expected to benefit from available therapies
- ECOG PS 0 or 1
Safety Results
- Grade 1 ICANS was reported in 2 patients (N=44).
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 09 February 2026.
References
| 1 | Chari A, Touzeau C, Schinke C, et al. Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1-2 study. Lancet Haematol. 2025;12(4):e269-e281. |
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