Utility and sensitivity of wett-SA53 to measure dysgeusia associated with talquetamab, a GPRC5D×CD3 bispecific antibody, in Relapsed/Refractory multiple myeloma: Preliminary data from the talisman study

Abstract Introduction: Talquetamab (Tal) is the first GPRC5D×CD3 bispecific antibody approved for the treatment of relapsed/refractory multiple myeloma (RRMM). Early onset of oral adverse events (AEs), including dysgeusia, have been reported with Tal and can impact patient (pt) quality of life. Further, the standard Common Terminology Criteria for Adverse Events (CTCAE) grading scale limits detailed assessment of dysgeusia. The TALISMAN study aims to better understand oral AEs, identify new tools for measurement, and investigate prophylactic interventions to prevent and/or limit the severity of Tal-related oral AEs. Here, we report preliminary data from the TALISMAN study. Methods:TALISMAN (NCT06500884) is an ongoing, phase 2, multicenter, global, randomized study. Eligible pts have RRMM and prior exposure to a proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody. At baseline, pts cannot have a “severe” score for dysgeusia per the Waterless Empirical Taste Test (WETT), a validated measure to identify various concentrations of taste stimuli. Pts are randomized to 1 experimental cohort (Tal plus an experimental prophylaxis) or the control cohort (Tal only). Experimental prophylaxes include dexamethasone [Dex] mouthwash, oral pregabalin, or clonazepam orally dissolving tablets. Pts receive prophylaxis starting 7 days before Tal step-up doses followed by Tal 0.8 mg/kg every other week. Tal dose may be reduced to every 4 weeks starting at cycle 5 for pts with a very good partial response or better (≥VGPR). 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). Here, we report data from the control and Dex prophylaxis cohorts. Results: As of July 7, 2025, 17 pts (8 in control and 9 in Dex prophylaxis) were randomized. Median age was 62 years and 47% were male; 65% were White, 18% were Black, and 18% were Asian. 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 (following 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. By the WETT scale, 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 dysgeusia 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 CTCAE 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). All initial pts (5/5) achieved a ≥VGPR by cycle 5 and remain on Tal at data cutoff. Additional pts and data including onset and resolution of dysgeusia, AEs, PROs, and biomarkers will be available at the time of presentation. Conclusions:In this randomized, phase 2 study utilizing the WETT SA-53 assessment tool for the first time in pts with MM,WETT scores appeared to be highly sensitive with the ability to objectively capture a broader spectrum of taste changes throughout Tal treatment compared with CTCAE grading. Preliminary data showed the WETT scale was able to detect dysgeusia, and importantly, objective improvements in dysgeusia by cycle 8. Results from this study will help characterize and guide management of dysgeusia associated with GPRC5D treatment and may establish the WETT assessment as an important objective tool for cancer agents impacting taste.