Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis
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Clinical Trial
Rapid response to single agent daratumumab is associated with improved progression-free survival in relapsed/refractory AL amyloidosis.
Background: Daratumumab is a monoclonal antibody, which targets CD38; an antigen expressed on malignant plasma cells in AL amyloidosis thus providing a rationale for its use. Method: Patients treated with daratumumab monotherapy (2016-2019) for relapsed/refractory systemic AL amyloidosis were identified from the database at the UK National Amyloidosis Centre. Results: Of 50 evaluable patients, haematological responses at 3 months were: CR - 19 (38%), VGPR - 14 (28%), PR - 9 (18%) and no response - 8 (16%). ⋯ Conclusion: Daratumumab monotherapy is effective in multiply-relapsed systemic AL amyloidosis and should be considered, if available, in patients who have not received prior daratumumab therapy. Responses are achieved rapidly and overall response rate was 84%. CR predicts overall survival whilst speed of response is predictive of a longer PFS.
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Randomized Controlled Trial Multicenter Study
Quality of life outcomes in APOLLO, the phase 3 trial of the RNAi therapeutic patisiran in patients with hereditary transthyretin-mediated amyloidosis.
Introduction: Hereditary transthyretin-mediated (hATTR) amyloidosis is a rare, fatal, multisystem disease leading to deteriorating quality of life (QOL). The impact of patisiran on QOL in patients with hATTR amyloidosis with polyneuropathy from the phase 3 APOLLO study (NCT01960348) is evaluated. Methods: Patients received either patisiran 0.3 mg/kg (n = 148) or placebo (n = 77) intravenously once every three weeks for 18 months. ⋯ At 18 months, patisiran improved Norfolk QOL-DN total score and three individual domains as well as COMPASS-31 total scores relative to baseline. Consistent benefits were also observed in the cardiac subpopulation. Conclusion: The benefits of patisiran across all QOL measures and the rapid deterioration observed with placebo, highlight the urgency in early treatment for patients with hATTR amyloidosis with polyneuropathy.
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Background: The aim of the present prospective study (ClinicalTrials.gov Identifier: NCT02111538) was to assess the prognostic value of phase angle (PhA), derived from bioimpedance vectorial analysis (BIVA), in patients affected by systemic amyloid light-chain (AL) amyloidosis. Methods: One hundred-twenty seven consecutive newly diagnosed, treatment-naïve patients with histologically confirmed AL amyloidosis were enrolled. Nutritional assessment including BIVA-derived PhA was performed before treatment initiation. ⋯ There was no effect modification of PhA on mortality by cardiac stage (P for interaction = 0.61). Conclusions: In AL amyloidosis, BIVA-derived PhA is associated with the common parameters implied in malnutrition assessment and QoL, and adjusted for hydration independently predicts survival. Due to its feasibility, BIVA should be systematically considered for the nutritional and clinical assessment of AL patients, in whom nutritional intervention trials are warranted.
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Background: Impaired aerobic capacity in cardiac amyloidosis patients may be related to limited inotropic myocardial reserve and heart rate (HR) response limiting cardiac output rise. This study sought to investigate whether chronotropic incompetence (CI) and blunted HR recovery would be prevalent in patients with mutant transthyretin (ATTRv) cardiomyopathy. Methods and results: Eighteen ATTRv (Val122Ile) patients (72 ± 8-year) and 15 age-matched controls (73 ± 3-year) were prospectively enrolled. ⋯ HR recovery, as percent decrease in peak HR at 1 and 3-min, was blunded ATTv patients. Conclusions: In Val122Ile ATTRv patients, chronotropic response was appropriate relative to exercise intensity with only few patients displaying CI. HR response to exercise was further characterised by blunted HR recovery in ATTRv patients suggesting lower parasympathetic activity and greater sympathetic stimulation compared with controls.