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Thirty percent of patients with head and neck squamous cell carcinoma (HNSCC) are at least 70 years of age. This number continues to rise as life expectancy continues to increase. Still, older adults with HNSCC remain underrepresented in clinical trials, resulting in ambiguity on optimal management. Older adults are a complex patient population, often requiring increased support due to issues relating to functional and performance status, medical comorbidities, and medication management. Furthermore, in older adults with HNSCC, many of these conditions are independently associated with increased toxicity and worse outcomes. Toxicity in the older adult remains difficult to predict and to understand, and as treatment decisions are based on treatment tolerability, it is essential to understand the toxicities and how to minimize them. Novel predictive scores are being developed specifically for older adults with HNSCC to understand toxicity and to assist in personalized treatment decisions. There are clinical trials presently underway that are investigating shortened radiation courses and novel, less toxic systemic treatments in this population. In the forthcoming sections, we provide a detailed overview of the clinical data, treatment paradigms, and considerations in this population. This review provides a comprehensive overview of existing clinical data and clinical considerations in the older adult head and neck cancer population. Additionally, we provide a detailed overview of pertinent current and ongoing clinical trials, as well as future areas for investigation.

Background: Talquetamab (JNJ-64407564) is a humanized IgG4 bispecific antibody that targets the CD3 receptor complex on T cells and G-protein-coupled receptor class 5 member D (GPRC5D) a transmembrane receptor protein overexpressed on malignant plasma cells in Multiple Myeloma. After 6.3 months of follow up in RRMM, talquetemab monotherapy at the recommended phase 2 dose yielded an overall response rate of 70%. Talquetemab was well tolerated and here we describe the presentation and management of dermatologic and oral adverse events (AEs) in 78 patients (pts) treated with talquetemab at a single center that is part of a multi-center, multi-national study. Methods: Eligible pts with RRMM were enrolled to the Phase 1, first in human, open-label dose escalation study (NCT03399799) at our site, and received talquetamab intravenously (IV; range 1.5µg/kg -1200µg/kg biweekly or weekly) or subcutaneously (SC; 5µg/kg to 800µg/kg weekly). AEs were graded using CTCAE v4.03. Results: As of July 2021, 78 pts received talquetamab, 53 (67.9%) by IV and 25 (32%) by SC route. Treatment emergent dermatologic AEs were observed in 20 (25.6%) pts. The most common AEs were palmar/plantar desquamation in 22 pts (28.2%, grade 1/2), nail disorders in 14 pts (17.9%, all grade 1), systemic rash in 11 patients (14%, grades 1-3), and injection site reaction in 7 pts (8.9%, all grade 1). Time of onset for dermatologic toxicities was generally within the first 30 days of therapy. In collaboration with dermatology consultation, the management of palmar/plantar desquamation, nail disorders, and injection site reaction has been ammonium lactate 12% cream, triamcinolone 0.1% cream, along with plain Vaseline and Vanicream products applied twice daily. Of the 11 pts with systemic rash, 10 were at or above a dose of 405 µg /kg. Five pts had grade 3 rash requiring dose hold and systemic steroids in conjunction with topical medications. All pts have resumed dosing without recurrence of grade 3 rash. Four of these pts were at a dose level of 800 µg/kg SC. Grade 1-2 rash did not require dose hold and was managed with early intervention of the 3 topical treatments applied to affected areas twice daily. In addition to the above described dermatologic AEs, treatment emergent oral AEs were observed in 38 (48.7%) pts, all grade 1-2. 42 pts developed dysgeusia (53.8%), 16 developed dry mouth (20.5%), and 17 developed dysphagia (21.8% ). Dysgeusia resulted in 3 pts requiring drug interruption. 1 pt requiring dose reduction, and 1 discontinued treatment. The average time to onset for dysgeusia was 26.5 days. Dry mouth resulted in no drug interruptions, reductions, or discontinuations, and had an average onset of 6.7 days. Dysphagia also ranged from grades 1-2, with 3 pts requiring drug interruption. There were no dose reductions or treatment discontinuation. The average time to onset was 41.5 days. Dry mouth, dysgeusia, and dysphagia were more prevalent with higher doses. Along with GI and nutrition consultation, oral AEs have been successfully managed with saliva substitute sprays and rinses. These supportive interventions are instituted promptly at time of onset of symptoms. The above-described treatments for dermatologic and oral AEs were not protocol mandated procedures. Discussion The dermatologic and oral AEs associated with talquetamab have unknown etiologies and are currently under investigation. These AEs are typically low grade, rarely require dose holds or modifications, and have been manageable with early and consistent supportive care. Only one patient to date at our center, has discontinued treatment due to an oral or dermatologic side effect. Talquetamab appears to have a have favorable risk/benefit profile in RRMM with durable responses and manageable toxicities. A standardized regimen of topical and oral supportive care appears to be beneficial in the management of dermatological and oral side effects. Disclosures Farrell: Regeneron: Current Employment. Florendo: Legend Biotech: Current Employment. Catamero: Celgene: Ended employment in the past 24 months, Honoraria; Legend: Honoraria; Oncopeptides: Speakers Bureau. Parekh: Foundation Medicine Inc: Consultancy; Amgen: Research Funding; PFIZER: Research Funding; CELGENE: Research Funding; Karyopharm Inv: Research Funding. Richter: Janssen: Speakers Bureau; Celgene: Speakers Bureau; Adaptive Biotechnologies: Speakers Bureau; Celgene: Consultancy; Janssen: Consultancy; BMS: Consultancy; Karyopharm: Consultancy; Antengene: Consultancy; Sanofi: Consultancy; X4 Pharmaceuticals: Consultancy; Oncopeptides: Consultancy; Adaptive Biotechnologies: Consultancy; Secura Bio: Consultancy; Astra Zeneca: Consultancy. Chari: Janssen Pharmaceuticals: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; Novartis Pharmaceuticals: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; Pharmacyclics: Research Funding; Seattle Genetics: Consultancy, Research Funding; Takeda Pharmaceutical Company: Consultancy, Research Funding; Karyopharm: Consultancy; Sanofi Genzyme: Consultancy; Oncopeptides: Consultancy; Antegene: Consultancy; Glaxosmithkline: Consultancy; Secura Bio: Consultancy.