SUMMARY  

• Janssen does not recommend the use of TALVEY in a manner that is inconsistent with the approved labeling.
• 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
  • Ataxia/balance disorder occurred in 4.1% of patients (n=14), of which 1.5% were grade 1, 2.4% were grade 2 and 0.3% were grade 3. No grade 4 or 5 events occurred.⁴ 
  • Chari et al (2025)³ published the incidence of ataxia leading to treatment discontinuation 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.

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.⁵ 
• Observed cases of ataxia and/or balance disorders have been identified in the broader adverse event (AE) category neurotoxicity.
• In a general clinical context, ataxia results from damage to the cerebellum or its connections, which leads to incoordination of movement.⁶ 
• The mechanism of talquetamab and ataxia/cerebellar ataxia is not known.⁷   
• It is important to note that many signs of cerebellar ataxia are not specific and may be caused by other conditions.⁸ 

CLINICAL DATA - Monumental-1 Study

MonumenTAL-1 (MMY1001; NCT03399799, NCT04634552) is a phase 1/2 study of TALVEY in patients with RRMM.^9,10

Study Design/Methods (Phase 2)

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

• 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 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, 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 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 days) from the first dose and 4 days (range 1-13 days) from the last dose, and 7 (38.9%) of 18 events did not resolve.⁴ 

Chari et al (2025)³ published the incidence of incidence of ataxia 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

• 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 according to the current practice guidelines.⁴ 

literature Search

A literature search of MEDLINE^®, Embase^®, BIOSIS Previews^®, and Derwent Drug File databases (and/or other resources, including internal/external databases) topic was conducted on 06 October 2025.