Milder Than Expected: Real-World Endocrine Toxicity Profile of Immune Checkpoint Inhibitors in Eastern Algeria

Abstract

The recent introduction of immune checkpoint inhibitors (ICIs) in Algeria in late 2024 has transformed the therapeutic landscape for multiple malignancies. While endocrine immune-related adverse events (irAEs) are well-documented globally, real-world data concerning their clinical presentation and severity in the Algerian population remain scarce. This study aims to report the initial experience of endocrine toxicity management following the introduction of PD-1 and PD-L1 inhibitors across a broad spectrum of cancers. We conducted an observational, real-world analysis within a medical oncology department in Eastern Algeria, enrolling patients initiated on ICI therapy since late 2024. The cohort comprised 84 patients distributed across various tumor types and regimens: 60 received pembrolizumab (23 triple-negative breast cancer, 17 non-small cell lung cancer, 9 renal cell carcinoma [RCC], 8 melanoma, 3 gastric cancer); 19 received nivolumab (5 pancreatic cancer, 4 urothelial carcinoma, 3 head and neck cancer, 5 RCC, 2 gastric cancer); 3 received avelumab (RCC); and 2 received atezolizumab (hepatocellular carcinoma). While various potential toxicities were monitored, particular attention was dedicated to endocrine side effects, which mandated the active involvement of endocrinologists in this surveillance framework. All toxicities were graded according to CTCAE v5.0 criteria. Endocrine irAEs were observed within the cohort, with dysthyroidism representing the most frequent manifestation and the primary driver for endocrinological referral. Strikingly, the clinical severity of these endocrine toxicities was notably lower than the profiles typically reported in the international literature. The majority of events were low-grade (CTCAE Grade 1-2), allowing for symptomatic hormonal substitution without necessitating ICI discontinuation. No high-grade (Grade 3-4) endocrinopathies, such as fulminant hypophysitis or adrenal crisis, were documented in this preliminary cohort. In this initial real-world experience from Eastern Algeria, the use of pembrolizumab, nivolumab, avelumab, and atezolizumab across various localizations demonstrates a manageable endocrine safety profile, with toxicities manifesting at a lesser severity than expected. These findings support a favorable risk-benefit ratio; however, the specific impact on thyroid function underscores that ongoing multidisciplinary surveillance—actively integrating endocrinologists—remains imperative to ensure prompt management and treatment continuity.