Safety Profile of Talquetamab in Relapsed or Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis

Talquetamab, a first-in-class bispecific T-cell engager (BiTE) targeting G protein-coupled receptor class C group 5 member D (GPRC5D), has emerged as an effective therapy for relapsed or refractory multiple myeloma (RRMM). However, its distinct mechanism of action and off-tumor, on-target expression in keratinized tissues generate a unique toxicity profile. Characterizing the incidence of immune-mediated, dermatologic, and oral adverse events (AEs) across pooled clinical cohorts is vital to optimizing supportive care strategies and real-world clinical delivery.

A systematic literature search was conducted across PubMed, ClinicalTrials.gov, Cochrane, and EMBASE to identify clinical studies evaluating talquetamab in RRMM. Pooled proportions and 95% confidence intervals (CI) for key treatment-emergent AEs were calculated using a random-effects model with inverse variance weighting and Freeman-Tukey double arcsine transformation. Heterogeneity across the included studies was quantified using the I² statistic and the Q test. Evaluated outcomes included cytokine release syndrome (CRS), dysgeusia/taste changes, skin-related AEs, nail-related AEs, rash, any-grade and grade ≥ 3 infections, immune effector cell-associated neurotoxicity syndrome (ICANS), and weight loss.

A total of 19 trials and retrospective studies published between 2024 and 2026 were included in the final analysis. Across analyzed studies, the pooled incidence of CRS was 59% (95% CI: 51%-66%; N = 1849) with substantial heterogeneity (I² = 88.6%, p < 0.01). Non-hematologic toxicities were common. Dysgeusia/taste changes occurred in 59% of patients (95% CI: 40%-76%; N = 1278, I² = 97.1%, p < 0.01). Skin-related AEs occurred in 60% (95% CI: 47%-72%; N = 2053,  I² = 96.0%, p < 0.01). Nail-related AEs occurred in 41% (95% CI: 28%-56%; N = 1933,  I² = 96.7%, p < 0.01). Rashes occurred in 22% (95% CI: 13%-33%; N = 994,  I² = 88.4%, p < 0.01). For infectious complications, the pooled incidence of any-grade infections was 42% (95% CI: 35%-49%; N = 1775,  I² = 86.9%, p < 0.01), while grade ≥ 3 infections were observed in 15% (95% CI: 10%-22%; N = 928,  I² = 73.4%, p < 0.01). ICANS demonstrated a low overall pooled rate of 8% (95% CI: 6%-11%; N = 1738,  I² = 49.6%, p < 0.01). Weight loss was reported in 37% of patients (95% CI: 25%-50%; N = 872,  I² = 92.4%, p < 0.01).

Talquetamab demonstrates a distinct toxicity profile characterized by high rates of mild-to-moderate CRS, dysgeusia, skin, and nail events, along with notable rates of weight loss and overall infections, accompanied by substantial statistical heterogeneity across studies. However, severe (grade ≥ 3) infections and ICANS remain relatively low. Proactive monitoring and standardized supportive interventions targeting oral and dermatologic side effects are essential to managing treatment burden and ensuring sustained clinical benefit in patients with RRMM.