Toxicity Management and Safety Profiles During Treatment of CSCC

Dr. Zeitouni compares immune-mediated adverse event rates across checkpoint inhibitor agents in advanced CSCC. Grade 3 or higher immune-mediated reactions have been reported in approximately 12% of patients with pembrolizumab and between 7% to 15% (and up to approximately 17% in some real-world data) with cemiplimab. Cosibelimab data show grade 3 or higher immune-mediated reactions occurring in less than 1% of patients, representing a meaningfully more manageable safety profile particularly relevant for patients with multiple comorbidities.

NP Schollenberger addresses grade 1 to 2 toxicity management, emphasizing that not all low-grade toxicities carry equivalent clinical significance. A grade 1 mild fatigue with normal cortisol, or a stable scattered pruritic rash manageable with topical steroids and antihistamines, represents a different risk profile than grade 1 diarrhea, which can rapidly escalate to grade 3 colitis requiring hospitalization, particularly in elderly patients who dehydrate quickly and have limited physiologic reserve.

Key principles include: recognizing which grade 1 to 2 symptoms are merely bothersome versus those with potential to escalate rapidly; understanding that elderly patients are not necessarily more likely to develop toxicities but will tolerate them less well; factoring in disease burden when deciding whether to push through manageable symptoms; and applying retrospective data on early discontinuation to avoid prolonged treatment beyond the point of clinical necessity. The inability to dose reduce checkpoint inhibitors, unlike cytotoxic agents, means that holding therapy and close monitoring are the primary management tools for emerging toxicities.

Dr. Hamid reinforces that the reduced physiologic tolerance of this elderly population is a frequently underappreciated clinical reality, and that toxicity thresholds should be lower than those applied in younger patients receiving immunotherapy for other indications.