The discrepancy between managing the disease and a disease management program in systemic melanoma therapy

Abstract

Dear Editors,

Given the improved survival of patients with advanced melanoma, especially after immune checkpoint inhibitor (ICI) therapy, long-term follow-up is critical to monitor and treat chronic immune-related adverse events (irAE). However, despite existing guidelines providing distinct recommendations, there may be hurdles to implementation in everyday clinical practice.^{1, 2} In internal medicine, disease management programs (DMP) pursue and successfully implement holistic therapeutic concepts, whereby this collaborative approach has reduced rehospitalizations and deaths, lowered healthcare costs, and improved patient responsibility through better interdisciplinary networking.³ Training for all cancer team members across specialist boundaries is essential for effective collaboration and optimizing patient outcomes.

In order to evaluate the need for (unmet) accompanying support (psychological, physiotherapeutic, social), we conducted a questionnaire-based analysis at our dermato-oncology center. A total of 72 questionnaires were completed. These included 14 questions regarding melanoma stage, treatment, associated events such as irAE or unplanned hospital stays due to acute deterioration of health status and the demand for additional services like physiotherapy or psychological counseling. Approximately 75% of patients received dermato-oncological care for up to 2 years, a quarter for more than 3 years. Common prior conditions included cardiac (43%), ophthalmological (26.4%) and joint disorders (20.8%). Immune checkpoint inhibitor therapy was the most common melanoma-specific treatment, administered in 82% of patients, followed by targeted therapy in 29%. Fourteen patients (19.4%) received both. Over half of all patients reported treatment-associated fatigue, followed by other commonly described irAE of systemic melanoma therapy (Table 1).

In case of irAE, patients most frequently turned to the dermato-oncology clinic first (48.6%), followed by general practitioners (11.1%) and dermatologists in private practice (8.3%). More than half of all patients required additional medical support during treatment, including 19 hospital admissions (26%) within the last 6 months before completion of the questionnaire. Patient satisfaction with outpatient dermato-oncological care was high: organization, accessibility, appointment coordination, and time management were rated as good or excellent by more than 80%. However, there was room for improvement regarding appointment coordination and time management in outpatient dermato-oncological care: around 10% of patients rated these services as only average and less than 1% as poor. Physiotherapy (51.4%), nutritional medicine (45.8%), melanoma education (18.1%) and psychotherapy (15%) were most frequently requested. Three key priorities from the patients’ perspective were interdisciplinary cooperation (59.7%), availability of additional care services (52.8%) and professional competence (47.2%) (Figure 1).

Our analysis confirms that more than half of patients receiving primarily ICI-based therapy experience fatigue and musculoskeletal symptoms, while approximately 40% of melanoma patients develop chronic side effects.⁴ Although these are often low-grade (CTCAE°1 or 2), they may persistently impact quality-of-life (QoL). Particularly in the adjuvant setting, careful risk-benefit analysis, prolonged monitoring and prompt management of potential irAE is therefore indicated.⁵ Routine provision of additional medical services such as physiotherapeutic, nutritional and psycho-oncological support is already recommended in national and international guidelines,^{2, 6} and is pre-requisite for skin cancer center certification according to standards of the German Cancer Society (DKG).⁷ Our survey revealed a demand for physiotherapy and dietary counselling in approximately 50% of patients. Physical exercise is a key element in managing cancer- and treatment-related fatigue, which was the AE most frequently reported in our patients as well as in pivotal ICI-studies in melanoma. Exercise programs are safe and feasible and are also recommended in certain guidelines even for patients with bone metastases.^{8, 9} The novel concept of prehabilitation (exercise before treatment) may further improve health outcomes.¹⁰

Nearly half of our patients sought dietary counseling. General evidence supporting its impact on QoL and survival in cancer patients is limited and current melanoma guidelines do not provide specific dietary advice.^{2, 6} However, since diet influences microbiome composition, several studies have investigated the effect of dietary habits and interventions (probiotics) on immunotherapy outcomes.^{11, 12} High-fiber and mediterranean-style diets (high in whole grains, fish, nuts, fruit and vegetables) are associated with improved response and survival as well as decreased frequency of AEs in metastatic melanoma patients undergoing checkpoint inhibition.^{11, 13} Conversely, antibiotics may adversely affect the gut microbiome, potentially imparing treatment efficacy. The benefits of over-the-counter probiotics for melanoma patients receiving immunotherapy remain uncertain.

Lastly, our survey showed that approximately 20% of melanoma patients requested further information regarding their disease. Treatment information can be improved through digital resources such as smartphone-apps and web-based therapy monitoring.¹⁴

The need for additional psycho-oncological support may be associated with the observed 20% rate of anxiety and/or sleep disorders. Kasparian et al. decribed that one third of long-term melanoma survivors need psychological intervention.¹⁵ Psychological interventions in cancer patients reduce distress, functional impairment and recurrence, while improving QoL.¹⁶

Cancer presents physical and psychosocial challenges; therefore, accessible psychological support should be prioritized. Our findings suggest that psycho-oncological support should be provided repeatedly during and after treatment, regardless of tumor stage or disease course.

Considering our data, highlighting potential challenges in routine implementation of existing guideline recommendations, a coordinated initiative regarding accompanying therapy concepts in ICI-treated melanoma patients at a national or European level would be desirable. As a first step, we developed the “CARE” concept – a newly designed algorithm for clinicians during and subsequent to checkpoint inhibitor treatment in melanoma (Table 2). This concept includes specific psycho-oncologic, physiotherapeutic, dietary and interdisciplinary networking advice. Each area is divided into three phases according to the acronym: Conversation, Advice and RE-evaluation, ensuring a standardized and patient-centered approach to care, designed to be easy-to-use in daily clinical practice.

In summary, advances in melanoma treatment have made long-term survival possible in an increasing number of certain patients, which on the downside may be accompanied by long-term side effects. In order to maintain QoL and minimize physical damage in these patients, comprehensive follow-up and interdisciplinary care are essential. Specific DMP addressing the needs of ICI-treated melanoma patients could be helpful in this context. Our survey revealed a strong demand for additional services accompanying immunotherapy, particularly regarding physical activity, psychological support and nutritional advice. We therefore created a specific algorithm to routinely provide our patients with the necessary assistance in a timely and standardized manner.

M.B.: relevant financial activities (speaker honoraria from Bristol-Myers Squibb, Pierre Fabre and Novartis, travel honoraria from Abbvie, Pierre Fabre and Novartis). P.K.: relevant financial activities (stock and other ownership interests from Bayer, BioNTech, Moderna Therapeutics, Valneva; speaker, advisory board honoraria from Bristol-Myers Squibb, Merck Sharp and Dohme, Novartis, Pierre Fabre, Sanofi Aventis GmbH).