Dermatological toxicities associated with talquetamab in RRMM

Talquetamab is a G protein-coupled receptor family C class 5 member D (GPRC5D) targeting bispecific antibody which was granted accelerated approval by the U.S. Food and Drug Administration and conditional marketing authorization by the European Commission. In both approvals, patients must have been treated with a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 antibody; making talquetamab the first GPRC5D-targeted bispecific antibody to be approved for use in relapsed/refractory multiple myeloma (RRMM).

Here, we summarize a retrospective study published by Lery et al.¹ in Journal of the American Academy of Dermatology on the dermatological toxicities associated with the use of talquetamab for the treatment of RRMM.

Study design/patient population¹

• A descriptive retrospective study conducted with patients treated in a single center from 2020–2022.
• The cohort consisted of 14 patients with RRMM who had been exposed to talquetamab.
• Eligibility criteria included both patients treated with talquetamab monotherapy or in combination.
• Doses of talquetamab included subcutaneous infusion between 300 μg/kg and 800 μg/kg, administered weekly or fortnightly.

Key findings¹

• Of the 14 patients enrolled, 12 developed dermatological toxicities, with an overall incidence of 86% in this small cohort.
• Nail changes were the most commonly occurring presentation, observed in 79% of patients, with onychomadesis in 57% (Figure 1).
• The most frequent toxicity observed was xerostomia, occurring in 71% of patients.
• Most toxicities were Grade 1 or 2, with no patients discontinuing treatment due to toxicities.
• The dermatological toxicity profile remained consistent, regardless of the dose of talquetamab or combination administered.
• In all cases, an improvement in hand-foot syndrome, xerosis, and fissures was achieved with skin-directed therapies, including high-potency steroids and moisturizers.

*Data from Lery, et al.¹

Key learnings

Dermatological toxicities were observed in most patients treated with talquetamab, regardless of dose or combination therapy. In most cases, the dermatologic toxicities were attributed to off-tumor on-target effects due to the high expression of GPRC5D in hard-keratinized structures such as the nails. This trial included a small cohort from a single center, making the data less generalizable. However, the findings highlight the need for further research in patients treated with talquetamab.