Taste Abnormalities Emerging during Anti-Myeloma Therapies Including GPRC5D x CD3 Bispecific Antibody Talquetamab

Background: Dysgeusia is a common, yet underexamined side-effect of anti-tumor therapy. In multiple myeloma (MM) it has received more attention recently with the introduction of talquetamab, a bispecific T-cell engaging antibody targeting GPRC5D. Although GPRC5D expression is mainly restricted to plasma cells, cornified tissues including some cells in the oral cavity also express GPRC5D. This expression could be associated with changes in taste perception in patients undergoing therapy with talquetamab. Abnormalities in taste perception can negatively affect patients' quality of life and nutritional status, and in some cases may even require treatment interruption with a potential negative impact on outcome. Our objective was to determine the quality and severity of dysgeusia and its impact on quality of life in MM patients treated with talquetamab. To take our findings into perspective, we compared these results to patients who received high-dose melphalan, a treatment which goes along with taste abnormalities frequently (positive controls) as well as with BCMA targeting bispecific antibodies for which taste abnormalities have not been reported thus far (negative controls). Methods: We used a validated diagnostic instrument, “Taste-Strips”, to objectively assess gustatory performance in all five qualities of taste (sour, sweet, bitter, salty and umami). Further, we used a validated diagnostic instrument, “Sniffin' Sticks Identification Test 16”, to identify possible changes in olfactory perception. In addition, we used a questionnaire to document subjectively perceived changes in taste perception, oropharyngeal symptoms, nutritional status, individual diet-related symptoms, therapy compliance and quality of life. Results: We enrolled 55 patients with MM in our study. Seven (13%) patients were treated with a GPRC5D bispecific. Twenty-one (38%) patients received a BCMA bispecific and 27 (49%) patients received melphalan. All patients receiving a GPRC5D bispecific responded to treatment but also reported a significantly impaired overall taste sensation. They were significantly more likely to report loss of appetite ( P<0.01; Fisher test), loss of bodyweight (GPRC5D bispecifics: -4.3kg (SD4.6); BCMA bispecifics: -0.3kg (SD2.0); melphalan: -2.8kg (SD2.8)) and dry mouth ( P<0.01; Fisher test). Futhermore, patients receiving a GPRC5D bispecific reported a severe to very severe subjectively perceived level of impairment in quality of life due to subjectively perceived changes in gustatory perception of sweet, bitter, umami, and salty flavors (in descending order; P<0.01; Fisher test) and dry mouth ( P<0.01; Fisher test) than patients receiving BCMA bispecifics or melphalan. Forty-eight% of patients on BCMA bispecifics and 59% of patients on melphalan reported some level of dysguesia, which was objectified by “Taste-strips”-testing, highlighting the overall underreported frequency of this side effect. Of note, melphalan patients reported nausea and vomiting significantly more frequently than the other groups ( P<0.01; Fisher test). Objective olfactory testing did not show significant differences in olfactory perception between patients who received GPRC5D bispecifics, BCMA bispecifics or melphalan. Conclusion: Our results demonstrate the importance of monitoring taste perception and quality of life changes caused by cancer therapies. The frequency of dysgeusia is underreported in MM patients receiving BCMA bispecifics and melphalan therapy. For optimal nutritional management, hospitals should consider patients' individual taste preferences.