ScholarWorks@성균관대학교

초록

Introduction. Talquetamab (Tal) is a GPRC5DxCD3 bispecific antibody approved for the treatment of relapsed/refrac-tory multiple myeloma (RRMM). Early oral adverse event (AEs) onset, including dysgeusia, can impact patient (pt) quality of life. The TALISMAN study aims to better understand oral AEs beyond standard Common Terminology Criteria for Adverse Events (CTCAE) grading limits, identify new measurement tools, and investigate prophylactic interventions. Here, we report preliminary data from the TALISMAN study (NCT06500884). Methods. Pts with RRMM and prior exposure to a protea-some inhibitor, immunomodulatory drug, and anti-CD38 antibody were included. Those with a baseline “severe” dysgeu-sia score per the Waterless Empirical Taste Test (WETT) were excluded. Pts were then randomized to the experimental (Tal + experimental prophylaxis) or control (Tal only) cohorts. Experimental prophylaxes include dexamethasone [Dex] mouthwash, oral pregabalin, or clonazepam tablets. Pts receive prophylaxis 7 days before Tal step-up doses, followed by Tal 0.8 mg/kg every other week. The 4 co-primary endpoints are the rate of occurrence of dysgeusia, rate of occurrence of severe dysgeusia, time to first onset of severe dysgeusia, and rate of resolution/improvement of dysgeusia at 3 and 6 months, as defined by the WETT score. Key secondary endpoints include change from baseline in sense of smell, safety and efficacy, and patient-reported outcomes (PROs) such as the Scale of Subjective Total Taste Acuity (STTA), which assesses overall acuity of taste based on a 4–point scale (0 reflects no change and 4 represents almost complete loss of taste). We report data from the control and Dex prophylaxis cohorts. Results. As of July 7, 2025, 17 pts (control, n=8; Dex prophylaxis, n=9) were randomized, and the median age was 62. Due to a pause in study enrollment for protocol updates, 2 groups are currently described: 5 initial pts (prior to enrollment pause; median follow-up [mFU], 240 days) and 12 additional pts (post-enrollment pause) of which data are available for 8 pts (mFU, 19 days). Dysgeusia onset data were available through cycle 1 for the total 13 pts. WETT scores tended to decline during cycle 1 with most pts (10/13) experiencing dysgeusia (WETT score <25th percentile) or severe dysgeusia (WETT score <10th percentile) by cycle 1 day 15, with majority (8/10) experiencing an immediate drop to severe dysgeusia; 2 pts had a step-wise drop from dysgeusia to severe dysgeusia by cycle 3. Further dys-geusia data were available only for the 5 initial pts: of 4/5 with dysgeusia, 2 had WETT scores that returned to normal (WETT score >26th percentile) and 2 had WETT scores that had not yet improved by cycle 8. In STTA analyses, preliminary data showed higher STTA scores, reflective of more severe perceived taste loss, during early cycles of Tal. By CT-CAE grading, 3/5 pts had grade 1 dysgeusia and 1/5 pts had grade 2 dysgeusia; other oral AEs included xerostomia (2/5 pts, all grade 1) and oral mucositis (1/5 pts, grade 1). Conclusions. In this study, WETT scores captured a broader spectrum of taste changes throughout Tal treatment versus CTCAE. Preliminary data showed WETT detected dys-geusia and objective improvements in dysgeusia by cycle 8. These results will help characterize and guide management of dysgeusia associated with GPRC5D treatment and may establish the WETT as an important tool.