Fonder, A C

Abstract 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 4396 patients with AL from 2010 to 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% vs 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 [mOS], 2.4 vs 5.1 vs 7.8 years for 3 vs 2 vs 1 layer); mOS was 6.8 years and was primarily driven by cardiac stage and hematologic response (very good partial response [VGPR] or better: hazard ratio, 0.20; 95% CI 0.13-0.32), with more favorable outcomes in patients with isolated GI involvement. Cachexia and persistent diarrhea were the main drivers of morbidity, need for nutritional support, and GI-related mortality (odds ratio, 2.7 for the combined end point). GI bleeding rarely recurred after achieving VGPR or better. Overall, mucosal involvement, cachexia, and dysmotility define clinically meaningful GI AL and support systematic assessment of autonomic dysfunction as well as evaluation of the need for nutritional support as a GI-specific end point for AL trials.

8019 Background: POEMS syndrome is a rare paraneoplastic syndrome caused by an underlying plasma cell disorder. Most of the information regarding treatment has been gleaned from retrospective data. The combination of a proteasome inhibitor, an IMiD and corticosteroid is known to be highly effective among patients with myeloma. Methods: We designed a pilot using a 28-day oral regimen of ixazomib (4 mg days 1, 8, 15), lenalidomide (25 mg days 1-21), and dexamethasone (20 mg days 1, 8, 15, 22). Aspirin and acyclovir were used for prophylaxis. Eligibility included a diagnosis of POEMS syndrome, a plasma VEGF > 200 pg/ml, a PS < 3. There were two groups [gp] (intended enrollment 15 per gp): Gp A, 13 cycles for patients (pts) who had relapsed or refractory disease; Gp B, 3 cycles for pts destined for high-dose chemotherapy with stem cell transplant. Primary endpoint was VEGF complete response (CR = normalization) after 3 cycles. Secondary endpoints included safety, hematologic response, and overall survival at 3 and 12 months. Other domains including PET response, clinical responses including neurologic response were also studied. To date, 13 pts enrolled since 10/31/2016—4 to Gp A and 9 to Gp B. 11 pts were analyzed (2 dropped out before receiving any therapy). Data were frozen as of 1/21/2019. Results: Median age was 55; 73% were male. So far, overall 64% met primary endpoint of VEGF CR (Table). The median follow-up of survivors is 12.4 mo (6, 24). 1 pt came off study for non-responsive disease and died thereafter. 38% of patients had grade 3+hematologic AE; 72% had grade 3-4 non-hematologic AE. These included: rash, respiratory infection and hypotension in 2 each; atrial fibrillation, diarrhea, edema, dyspnea, and thromboembolism in 1 each. 4 pts had non-objective worsening of their neuropathy. Conclusions: These preliminary results suggest that Ixa-Len-Dex is an effective and tolerable regimen for patients with POEMS syndrome. Clinical trial information: NCT02921893. [Table: see text]