FAITH: Fatigue associated with immunotherapeutics—Analyzing patterns and associated factors during treatment.

Abstract

e24065 Background: Fatigue is a frequent, multifactorial toxicity in patients receiving immune checkpoint inhibitors (ICIs), but its drivers and severity patterns remain poorly characterized in real-world practice. We analyse the incidence, attribution, and predictors of fatigue in this LMIC cohort, so that potentially preventable and reversible causes can be identified and addressed. Methods: We conducted a single-centre retrospective chart review of adults with solid malignancies who received ≥4 cycles of ICI therapy between January 2023 and December 2025. Demographic, clinical data, the highest CTCAE v5.0 fatigue grade per patient and contemporaneous clinical notes were reviewed. Descriptive analytics, Chi Square/Mann-Whitney U tests were used where appropriate and univariate analyses were used for exploratory screening. Results: 264 patients with solid malignancies who received ≥4 cycles of ICI therapy were included. Median age was 62 years (range 38–89), 42% were female, 83% with metastatic disease and 53% had ECOG PS-2. Treatment regimens included chemo–immunotherapy in 66%, tyrosine kinase inhibitor–ICI combinations in 22%, and ICI monotherapy in 12%. The most common malignancies were lung (22%), gastrointestinal & hepatobiliary (25%) and head and neck (14%). All-grade fatigue was reported in 90% of patients (n=238), with grade ≥3 in 69 (26%) patients. Median time to onset of worst-grade fatigue was comparatively shorter in the chemo–immunotherapy group (6 vs 8 weeks). On qualitative assessment, 90% patients reported a loss of appetite, 61% reported a new-onset sleep disturbance and only 31% engaged in exercise and physical activity. Overlapping etiologic attribution included chemo-immunotherapy (66%), hematologic causes requiring growth factors & transfusions (35%), dyselectrolytemia (26%), infections (23%), worsening comorbidities (18%) and endocrine irAEs (16%). ≥2 simultaneous contributing factors were identified in 15%. ICI related asthenia (diagnosis of exclusion) presented in 7% patients and responded to temporary treatment stoppage. Treatment was interrupted in 55% patients due to fatigue, and 35% could be restarted. 18% had a progression event on treatment. On univariate testing, chemoimmunotherapy, irAEs, cytopenias, age ≥65, ≥2 comorbidities, and poor sleep were associated with grade ≥3 fatigue (p<0.05). More than half of the patients had reversible causes, which included electrolyte disturbances, cytopenias, endocrine dysfunction, and infection. Conclusions: Systematic evaluation using a triage checklist of electrolyte, endocrine, infectious and hematological surveillance can help pinpoint causes of disproportionate fatigue. Earlier causal identification can avoid morbidities, unnecessary admissions and treatment interruptions, thus enabling better quality of life and facilitating better patient communication.