Gastrointestinal (GI) involvement is a clinically relevant but undercharacterized manifestation of systemic light chain amyloidosis (AL). We aimed to define the clinical spectrum, histologic patterns, and outcomes of symptomatic GI involvement in AL. We retrospectively analyzed 4,396 patients with AL 2010-2024, of whom 521 (11.9%) had provider-attributed symptomatic GI involvement; 66% had biopsy-proven GI AL. Symptoms most commonly included early satiety (61%), bowel irregularities (58%), nausea (35%), abdominal pain (28%), and dysphagia (23%). Autonomic neuropathy was frequent (43% clinician-attributed; 23% via autonomic reflex testing) and contributed to dysmotility-related symptoms, often without GI-biopsy positivity. Among 747 GI-biopsies, mucosal infiltration predominated (71%) and was associated with bleeding (22% versus 9%), cachexia, and inferior survival, whereas vascular involvement was associated with lower bleeding risk. Combined involvement of mucosa, submucosa, and vessels conferred the worst prognosis (median overall survival 2.4 versus 5.1 versus 7.8 years for three versus two versus one layer). Median overall survival was 6.8 years and was primarily driven by cardiac stage and hematologic response (≥VGPR: HR 0.20, 95%), with more favorable outcomes in patients with isolated GI involvement. Cachexia and persistent diarrhea were main drivers of morbidity, need for nutritional support, and GI-related mortality (OR 2.7 for combined endpoint). GI bleeding rarely recurred after achieving ≥VGPR. Overall, mucosal involvement, cachexia, and dysmotility define clinically meaningful GI AL and support systematic assessment of autonomic dysfunction as well as the evaluation of need for nutritional support as GI-specific endpoint for AL trials.
Steinhardt et al. (Thu,) studied this question.
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