D3.46 - Safety of the EAACI risk assessment in hypersensitivity reactions to chemotherapy

Hypersensitivity reactions (HR) to chemotherapeutics (CHT) are a major health issue. Diagnosis is complex due to heterogeneous phenotypes. While initial reaction severity is not always predictive, data on drug provocation tests (DPT) in moderate-severity cases are scarce. We aimed to validate the EAACI risk assessment (RA) algorithm in patients with suspected immediate HR to platinum salts (PS) and taxanes (TX).

Prospective study (Jan 2023–Dec 2024) of oncology patients with immediate HR to PS/TX. RA followed EAACI guidelines, including clinical history (Type-I, Cytokine Release Reaction [CRR], mixed, or indeterminate if unable to fit), severity (Brown classification), comorbidities, skin tests (ST), and basophil activation test (BAT). Low-RA patients underwent DPT; high-RA patients underwent 3-bag-12-step desensitization (DS).

101 patients (73.3% female; mean age 57.2±11.3 years) were evaluated: 34.7% TX (paclitaxel/docetaxel) and 65.3% PS (oxaliplatin/carboplatin/cisplatin). Stage IV cancer: 40.6%; atopy: 31.0%. ST were negative in 67.0%, BAT negative in 59.4%. Initial severity was moderate in 46.5% (TX: 62.9% vs. PS: 37.9%). Initial phenotypes: Type-I (37.6%), indeterminate (34.7%), and CRR (16.8%). RA classified 45.5% as low-risk and 54.5% as high-risk. DPT (n=30; 29.7% of cohort) showed 73.3% tolerance (100% in TX). DPT-positive patients (26.6%) were mostly initial Type-I with mild initial severity (6/8); no grade-3 reactions occurred during DPT. DS (n=58; 57.4% of cohort) resulted in 60.3% no reaction. Reactions during DS (n=22) occurred mainly with PS (77.3%) and initial Type-I (45.4%), with only one grade-3 reaction. Comorbidities did not significantly increase risk. Final phenotypes: non-hypersensitive (40.6%), IgE-mediated (24.0%), Mixed (11.5%), inconclusive (11.5%), Type-I non-IgE-mediated (8.3%), and CRR (4.2%).

The EAACI-RA algorithm is safe and useful. Low-risk patients showed high DPT tolerability (73.3%), and DS was effective for high-risk cases (60.3%), with mostly mild breakthrough reactions. Moderate initial reactions—the most frequent presentation—had excellent outcomes in TX but required closer monitoring in PS, where IgE-mediated phenotypes predominated.