# On-target, off-tumor oral toxicities of talquetamab in heavily pretreated multiple myeloma

## TL;DR

Talquetamab, a new treatment for multiple myeloma, is effective but causes persistent oral side effects that can harm patients' quality of life.

## Contribution

This paper reviews the features and management of oral toxicities caused by talquetamab in multiple myeloma patients.

## Key findings

- Oral toxicities like dysgeusia and dry mouth occur in over 70% of patients treated with talquetamab.
- These side effects often persist and can lead to significant weight loss and reduced quality of life.
- Current management strategies are largely supportive and not very effective, prompting trials of new preventive approaches.

## Abstract

Talquetamab (TAL), a first-in-class bispecific antibody targeting GPRC5D and CD3, has demonstrated high efficacy in heavily pretreated relapsed and refractory multiple myeloma (RRMM), achieving response rates of approximately 70%. However, TAL is frequently associated with on-target, off-tumor oral toxicities.

This study aimed to review the features of oral toxicities related to TAL.

A comprehensive review of the recent literature on TAL-associated oral toxicities was conducted. Extracted data included time to onset, incidence, severity grading, and reported management strategies for these adverse events.

Oral effects are hypothesized to arise from immune activation against epithelial cells expressing GPRC5D in the tongue, salivary glands, and hard keratinized tissues. Clinical studies, including the MonumenTAL-1 trial, have reported dysgeusia in up to 72% of patients, dry mouth in 39%, and dysphagia in 24% of patients. Such toxicities typically arise within a few weeks of initiating TAL therapy and tend to persist. They can significantly impair nutrition and quality of life, often leading to weight loss exceeding 6% of baseline body weight. Current management is largely supportive, including corticosteroid mouthwashes, saliva stimulants, nutritional counseling, and TAL dose adjustments, with limited efficacy. The ongoing TALISMAN trial is evaluating prophylactic interventions such as dexamethasone mouthwash and pregabalin.

Oral toxicities often emerge early and may persist throughout the therapy. Consequently, early recognition, preventive care, and multidisciplinary management are essential to mitigate oral complications and preserve quality of life in patients receiving TAL.