TALVEY – Occurrence and Management of Ataxia and/or Balance Disorders

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.
• 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).^1-3
  • In MonumenTAL-1 (N=375), at a clinical cutoff date of October 2024, ataxia/balance disorders were reported in 5% of patients (n=18).⁴
  • Chari et al (2025)³ published the incidence of ataxia/balance disorders 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 Q2W cohort, and 16.8 months for the prior T-cell redirecting therapy (TCR)-exposed cohort. At a clinical cutoff date of October 2023, ataxia/balance disorders were reported in 1 patient in the 0.8 mg/kg SC Q2W cohort.
• MonumenTAL-3 is a phase 3 randomized, open-label, multicenter study comparing the efficacy of TALVEY in combination with DARZALEX FASPRO^® (daratumumab hyaluronidase; Tal-D) or TALVEY in combination with DARZALEX FASPRO and pomalidomide (Tal-DP) vs DARZALEX FASPRO in combination with pomalidomide and dexamethasone (DPd) in patients with RRMM.^5,6
  • Mina et al (2026)^6,7 published the incidence of ataxia/balance disorder events from the MonumenTAL-3 study at a median follow-up of 24.6 months. At the clinical cutoff date of November 2025, ataxia/balance disorders were reported in 12.4% of patients (n=34) in the Tal‑D arm, 14.5% of patients (n=40) in the Tal‑DP arm, and 0.4% of patients (n=1) in the DPd arm.
• RedirecTT-1 is an ongoing, open-label, phase 1b/2 evaluating the safety and efficacy of TALVEY and TECVAYLI^® (teclistamab-cqyv) in patients with RRMM, including those with extramedullary disease (EMD).⁸
  • At the clinical cutoff date of March 2025, ataxia/balance disorder events were reported in 0.9% of patients (n=1) in the phase 1 study (median duration of follow-up of 31.6 months) and in 1.1% of patients (n=1) in the phase 2 study (median duration of follow-up of 12.6 months).⁹
• TriMM-2 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.¹⁰
  • At a median follow-up of 17.25 months (clinical cutoff date of April 2025), ataxia/balance disorder events were reported in 9.2% of patients (n=6) in the TALVEY 0.4 mg/kg QW/ 0.8 mg/kg Q2W + DARZALEX FASPRO cohort and in 11.7% of patients (n=9) in the TALVEY 0.4 mg/kg QW/0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort.^11,12
• Other relevant literature has been identified in addition to the data summarized above.^13,14

BACKGROUND

• Clinical symptoms of ataxia include, but are not limited to, difficulty with walking and balance, falls, dizziness, blurred vision, slurred speech and clumsiness. Cerebellar signs include nystagmus, dysarthria, dysmetria, and gait ataxia.¹⁵ 
• Observed cases of ataxia and/or balance disorders have been identified in the broader adverse event (AE) category neurologic toxicity.
• In a general clinical context, ataxia results from damage to the cerebellum or its connections, which leads to incoordination of movement.¹⁶ 
• The mechanism of talquetamab and ataxia/cerebellar ataxia is not known.¹⁷   
• It is important to note that many signs of cerebellar ataxia are not specific and may be caused by other conditions.¹⁸ 

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^19,20

Study Design/Methods (Phase 2)

Patients were enrolled into 1 of the following 3 cohorts^1,21:

• 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 criteria³:
  • ≥18 years of age, measurable multiple myeloma (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.

Incidence of ataxia

• In MonumenTAL-1 (N=375), ataxia/balance disorder occurred in 5% of patients (n=18). Ataxia/balance disorder events were grade 1 (2.1%), grade 2 (2.1%), and grade 3 (0.5%). No grade 4 or 5 events occurred. The most frequent clinical manifestations of ataxia/balance disorder reported were dysarthria (1.3%), gait disturbance (1.9%), and balance disorder (1.1%), and 0.5% of patients experienced more than one ataxia/balance disorder event. The median time to onset was 148 days (range 6-894 days) from the first dose and 4 days (range 1-22 days) from the last dose, and 9 (43%) of 21 events did not resolve.⁴

Chari et al (2025)³ published the incidence of ataxia/balance disorders from a post hoc analysis 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

• At a clinical cutoff date of October 2023, one patient in the 0.8 mg/kg SC Q2W cohort had grade 2 cerebellar toxicity (reported as ataxia), which led to treatment discontinuation.

Management of Ataxia/Balance Disorder

• At the first sign of ataxia/balance disorder, withhold TALVEY, immediately evaluate the patient, and consider neurology evaluation. Rule out other causes of neurologic symptoms and provide supportive care based on severity; withhold or permanently discontinue TALVEY based on severity and consider further management per the current practice guidelines. See Table: Recommendations for Management of Neurologic Toxicity (Excluding ICANS).⁴

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.^5,6

Study Design/Methods

• Key eligibility criteria⁶: ≥18 years of age with measurable RRMM; ≥1 prior LOTs, including lenalidomide and a PI; ECOG PS 0-2.

Safety Results

Mina et al (2026)^6,7 published the incidence of ataxia/balance disorder from the MonumenTAL-3 study at a median follow-up of 24.6 months (range, 0.03-35.4).

• At a clinical cutoff date of November 2025, ataxia/balance disorders were reported in 12.4% (n=34) in the Tal‑D arm, 14.5% of patients (n=40) in the Tal‑DP arm, and 0.4% (n=1) in the DPd arm.
• Ataxia/balance disorders events in the Tal-D vs Tal-DP arms:
  • Ataxia: 5.1% (n=14) vs 5.4% (n=15)
  • Dysarthria: 4% (n=11) vs 4.3% (n=12)
  • Balance disorder: 2.6% (n=7) vs 2.9% (n=8)
  • Nystagmus: 0.4% (n=1) vs 2.9% (n=8)
  • Cerebellar ataxia: 0.4% (n=1) vs 1.4% (n=4)
  • Cerebellar syndrome: 0.4% (n=1) vs 1.1% (n=3)
  • Dysmetria: 0% vs 0.4% (n=1)
  • Gait disturbance: 3.6% (n=10) vs 2.9% (n=8)
• Gait disturbance was reported in 0.4% of patients (n=1) in the DPd arm.
• Grade 3 events were reported in 2.2% of patients (n=6) in the Tal‑D arm and 2.9% of patients (n=8) in the Tal‑DP arm; no grade ≥4 events were reported.
• Ataxia/balance disorder events led to:
  • TALVEY dose delays or skips in 8.4% of patients (n=23) in the Tal‑D arm and 7.6% of patients (n=21) in the Tal‑DP arm.
  • TALVEY treatment discontinuation in 2.2% of patients (n=6) in the Tal‑D arm and 4.7% of patients (n=13) of patients in the Tal‑DP arm.
  • Discontinuation of all study treatment in 2.5% of patients (n=7) of patients in the Tal‑DP arm.
• The median time to onset of ataxia/balance disorders from the 1^st dose of study treatment was 326 days (range, 24-873) in the Tal-D arm, 292 days (range, 3-1034) in the Tal-DP arm, and 21 days (range, 21-21) in the DPd arm.
• The median duration was 108 days (range, 1-385) in the Tal-D arm and 106.5 days (range, 10-808) in the Tal‑DP arm.
• As of the clinical cutoff date of November 2025:
  • A total of 65 events were reported in the Tal-D arm, 93 events in the Tal-DP arm, and 1 event in the DPd arm.
  • A total of 11 events (16.9%) in the Tal-D arm and 10 events (10.8%) in the Tal-DP arm were recovered or resolved.

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

RedirecTT-1 (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, including those with EMD.⁸

Study Design/Methods

• Key eligibility 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.⁸

Safety Results

• Ataxia/balance disorders were reported in patients receiving TALVEY in the RedirecTT-1 study.⁹
• At the clinical cutoff date of March 18, 2025, the median duration of follow-up was 31.6 months [range, 0.5+ to 49] in phase 1 and 12.6 months (range, 0.5+ to 19.5) in phase 2.⁹
• In the phase 1 study, as of the clinical cutoff date (N=114), grade 2 dysarthria was reported in 0.9% of patients (n=1), which led to dose interruption.⁹
• In the phase 2 study, as of the clinical cutoff date (N=90), grade 3 gait disturbance was reported in 1.1% of patients (n=1), which started after administration of the last treatment dose.⁹

CLINICAL DATA - TRIMM-2 study

TriMM-2 (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.¹⁰

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.

• At the clinical cutoff date of April 2025 (median follow-up of 17.25 months [range, 0.2- 54.7], ataxia/balance disorders were reported in 9.2% of patients (n=6) in the TALVEY 0.4 mg/kg QW/ 0.8 mg/kg Q2W + DARZALEX FASPRO cohort and in 11.7% of patients (n=9) in the TALVEY 0.4 mg/kg QW/ 0.8 mg/kg Q2W + DARZALEX FASPRO + pomalidomide cohort.^11,12
• Summary of ataxia/balance disorder events in both cohorts is presented in Table: TriMM-2 Study: Summary of Treatment-Emergent Ataxia/Balance Disorders.^11,12

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 17 August 2026.