Dermatologic adverse effects with elranatamab mimicking talquetamab

Abstract Bispecific antibodies (BsAbs) have become an important therapeutic option for patients with relapsed/refractory multiple myeloma (RRMM), offering an off-the-shelf alternative to CAR T-cell therapy (Lancman et al, 2021). Talquetamab, a GPRC5D-targeting BsAb, is known to cause distinctive dermatologic toxicities, including xerosis, maculopapular rash, nail dystrophy, palmar/plantar desquamation, and dysgeusia, effects attributed to GPRC5D expression in keratinized tissues (Narayan et al, 2023). Such effects have not been reported with BCMA-directed agents like Elranatamab. In this retrospective study, we identified seven out of 64 patients (11%) treated with Elranatamab at our center between October 2023 and May 2025 who developed dermatologic toxicities resembling those described with Talquetamab. Reported toxicities included xerosis with peeling (6/7), pruritic maculopapular rash (5/7), and onychodystrophy (2/7). The median onset was 32 days after Elranatamab initiation (range: 10–66 days). Two patients experienced associated dysgeusia, appetite loss, and weight loss. Management strategies included topical emollients and corticosteroids, with dose interruption or reduction in severe cases. Toxicities resolved in most patients within a median of 26 days. However, two patients discontinued Elranatamab due to persistent or recurrent side effects. Histologic evaluation in one case revealed interface dermatitis with eosinophils, supporting a drug-related mechanism. For comparison, we reviewed dermatologic events in 77 patients treated with Teclistamab during the same period. Only one patient (1%) developed a mild upper body maculopapular rash, and five patients (6%) developed injection site skin reaction. These findings suggest that Elranatamab may trigger Talquetamab-like skin toxicities, possibly through shared cytokine-driven inflammation or off-tumor BCMA activity in the skin. This is the first reported series describing dermatologic toxicities with Elranatamab resembling those of GPRC5D-targeting agents. As BsAbs are increasingly used earlier in the myeloma treatment algorithm, early recognition and proactive management of skin-related toxicities are essential to avoid treatment delays and improve patient tolerability.