Dermatologic toxicities associated with talquetamab in patients with Relapsed/Refractory multiple myeloma: A systematic review and meta-analysis

Abstract Introduction Multiple myeloma (MM) is an incurable malignancy, and the management of relapsed/refractory (RR) cases presents significant therapeutic challenges. Monoclonal antibodies are emerging as a promising treatment modality for patients who have exhausted earlier lines of therapy. Talquetamab, a bispecific antibody targeting CD3 and GPRC5D, has demonstrated encouraging efficacy in heavily pretreated patients, both as a monotherapy and in combination with other therapeutic agents. However, its administration is associated with a distinctive adverse effect profile. This systematic review and meta-analysis aims to evaluate the characteristics and incidence of cutaneous toxicities in patients with RR MM who are treated with talquetamab. Methods A systematic literature search was performed across several databases, including PubMed, Embase, the Cochrane Library, and relevant conference abstracts, for studies published up to June 2025. The methodology followed Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Inclusion criteria comprised randomized controlled trials (RCTs) and observational studies that enrolled adult patients with RR MM receiving talquetamab, either as a single agent or in combination with other therapies. The primary outcome of this analysis was the incidence of dermatological toxicity, comprising both cutaneous rash and other non-rash manifestations. Secondary outcomes included the occurrence of nail toxicities, taste disorders, infections, and cytokine release syndrome (CRS). Pooled data were summarized as overall proportions, presented with their respective 95% confidence intervals (95% CI). All statistical analysis were performed using R software (version 4.4.3). Heterogeneity among studies was evaluated using random-effects models and assessed by the I2 statistic, with a value less than 25% being indicative of low heterogeneity. Results A total of 8 studies comprising 816 patients were included in this analysis: 4 RCTs and 4 observational studies. Of these, 3 studies (n=194 patients) utilized combination therapy (talquetamab with daratumumab, teclistamab, or pomalidomide), while 5 studies (n=622 patients) administered talquetamab as a monotherapy. The doses ranged from 0.2 mg/kg to 0.8 mg/kg. The median age of the patient population was 65.8 years (range 24-85), and 57.7% were male. Patients had received a median of 5.2 prior lines of therapy, and their characteristics included 37.6% with high-risk cytogenetics and 76.9% with triple-refractory disease. The results of the pooled analysis indicated that the overall incidence of all-grade skin toxicities was 46.9% (95% CI 27–67; p<0.0001), demonstrating substantial heterogeneity (I2=92.5%). In a subgroup analysis, the incidence was 45.8% for studies using monotherapy (95% CI 17–77; p<0.0001; I2=95.2%) and 49.5% for those using combination therapy (95% CI 36–62; p=0.04; I2=67.5%). The pooled incidence of skin rash was 34.1% (95% CI 30–38; p=0.12; I2=51.5%). Of the 314 reported skin events, rashes were observed in 171 patients (54.4%). The grade of skin reactions was reported in only half of the included studies, with the majority of documented cases classified as Grade 1-2. In total, 14 out of 446 patients (3.1%) across 4 studies experienced toxicities of Grade ≥3. The pooled incidence of nail toxicities was 51.5% (95% CI 44–58; p=0.08; I2=50.9%), while taste disorders occurred in 71.9% of patients (95% CI 68–74; p=0.63; I2=0%). Infections were observed in 59.1% of patients (95% CI 43–73; p<0.0001; I2=88.6%), and CRS occurred in 69.9% (95% CI 62–76; p=0.002; I2=68.6%). Dose modifications were required for 20 patients (6.6%) out of 300 reported skin events across 2 studies. Only 1.6% of the 669 treated patients required treatment discontinuation attributed to skin or nail toxicities. Conclusion Our findings demonstrate a high incidence of dermatologic on-target/off-tumor toxicities with talquetamab in patients with RR MM, predominantly low-grade (Grade 1-2), with acceptable tolerability and a low risk of treatment discontinuation. The frequency of skin toxicities did not differ significantly between monotherapy and combination therapies. The limited reporting on the grading of skin toxicities highlights the need for further research to more comprehensively define the spectrum of talquetamab-associated adverse events in a clinical setting.