Taste and Smell Dysfunction in Patients More Than Two Years After Start of Immune Checkpoint Inhibitor Therapy

Background of the study: Immune checkpoint inhibitors (ICIs) are widely used as treatment for multiple cancer types and the number of patients with longterm disease control after ICIs is increasing. However, the use of ICIs is associated with adverse events (AEs) which can have a negative impact on quality of life (QoL). These AEs include oral manifestations, like alterations in taste and smell, xerostomia, and oral mucosal disorders, and could lead to unwanted weight loss. However, the characteristics of taste and smell dysfunction and xerostomia after treatment with ICIs are unknown. More insight in this phenomenon should be gained to make health care professionals aware of this problem to help patients cope with these AEs. Objective of the study: To determine the prevalence of taste and smell dysfunction in patients more than two years after ICI therapy - compared with a control group of caregivers. Secondary objective: to assess the association between taste and smell dysfunction, and saliva secretion rate, saliva composition (pH, electrolyte and protein composition) and subjective feeling of a dry mouth (xerostomia) in patients more than two years after start of ICI therapy - compared with a control group of caregivers. Study design: Observational cross-sectional study. Study population: Patients (aged \>18 years) with melanoma, non-small cell lung cancer (NSCLC) or urogenital cancers who have finished treatment with an ICI (CTLA-4 inhibitor, PD-(L)1 inhibitor, or both) \>2 years ago, and their caregivers. Primary study parameters/outcome of the study: Taste and smell dysfunction, measured using taste strips and Sniffin' Sticks. Secondary study parameters/outcome of the study: Salivary flow rate, salivary pH, proteins and electrolytes, xerostomia, and perceived taste and smell dysfunction and impact of taste and smell dysfunction. Nature and extent of the burden and risks associated with participation, benefit and group relatedness (if applicable): Participation in the study will include one study visit of approximately 1,5 hours. If possible, the study visit will be combined with a regular follow-up visit. In this study, no invasive procedures will be performed.

Sex

All

Minimum age

18 Years

Inclusion Criteria:

* 1\. Patients with melanoma, NSCLC or urogenital cancers \> 2 years since treatment with at least one cycle of immune checkpoint inhibitor (CTLA-4 inhibitor, PD-(L)1 inhibitor, or both) within the Department of Medical Oncology or Pulmonary Oncology of the UMCG.
* 2\. Age \>18 years at time of immune checkpoint inhibitor treatment
* 3\. Understand or abide to the study procedures
* 4\. Have given informed consent

A caregiver must meet all of the following criteria:

* 1\. Age \>18 years
* 2\. Understand or abide to the study

Exclusion Criteria:

* 1\. As previous or subsequent therapies, only surgery and palliative radiotherapy is allowed (excluding radiotherapy in the head-neck and brain region)
* 2\. Previous treatment in the past ten years for malignancy other than melanoma (excluding non-melanoma skin cancer, cervical intra-epithelial neoplasia (CIN) or carcinoma in situ of breast) (for patients: other than current malignancy)
* 3\. History of ear-nose-throat disease or auto-immune disorder affecting taste, smell, mouth mucosa, or saliva production (for patients: before start ICI)

• DERIVEDvan Elst JM, Buffinga CM, Brand HS, Hijmering-Kappelle LBM, Jager-Wittenaar H, Reyners AKL, Nuver J, de Haan JJ. Prevalence and characteristics of persistent taste and smell dysfunction after immune checkpoint inhibitor therapy for cancer. Support Care Cancer. 2026 May 21;34(6):564. doi: 10.1007/s00520-026-10761-4. PMID 42165900