Author + information
- Michaela Liedtkea,b,
- Raymond Comenzoa,b,
- Heather Landaua,b,
- Vaishali Sanchorawalaa,b,
- Brendan Weissa,b,
- Jeffrey Zondera,b,
- Jackie Wallinga,b,
- Gene Kinneya,b,
- Martin Kollera,b,
- Dale B. Schenka,b,
- Spencer Guthriea,b,
- Enchi Liua,b and
- Morie Gertza,b
Background: Current therapies used to treat AL amyloidosis limit light chain (LC) production but do not directly target deposits underlying multiorgan failure. NEOD001, a monoclonal antibody, targets misfolded LC and is thought to neutralize circulating LC aggregates and to clear insoluble deposits. Here we report results from the dose-escalation and expansion phases of this study.
Methods: In the dose-escalation phase of this trial, 27 patients were enrolled who completed ≥1 anti-plasma cell systemic therapy, had at least a partial hematologic response to any previous therapy, and had persistent organ dysfunction and received 0.5-24 mg/kg NEOD001 intravenously every 28 days (3+3 study design). Another 42 patients, including those with peripheral neuropathy, were enrolled and treated (24 mg/kg) in the expansion phase. We assessed safety/tolerability, pharmacokinetics, immunogenicity, cardiac and renal responses based on consensus criteria, and neuropathy responses using the Neuropathy Impairment Score-Lower Limbs (NIS-LL).
Results: The median time since last plasma cell therapy was 18 months. In a best response analysis of patients with evaluable cardiac or renal involvement, 53% (n = 19/36) met criteria for cardiac response and 63% (n = 22/35) met criteria for renal response. The remainder met best response criteria for stable disease. The median time to cardiac response was ∼2 months. In patients with peripheral neuropathy at baseline, 82% (9/11) demonstrated response after 9 months of treatment. Peripheral neuropathy completely resolved on the NIS-LL (ie, scores of 0 at the month 10 visit) in 2 patients.
Conclusions: Our interim results demonstrated that monthly NEOD001 infusions were safe and well tolerated, with organ response rates comparing favorably those of with traditional chemotherapy. Antibody therapy may allow for effective treatment of patients with AL amyloidosis and persistent organ dysfunction despite hematologic response or in concert with existing plasma cell-directed therapy as part of initial treatment.
Poster Hall, Hall C
Saturday, March 18, 2017, 9:45 a.m.-10:30 a.m.
Session Title: Advances in HCM, PPCM and Other Cardiomyopathies
Abstract Category: 13. Heart Failure and Cardiomyopathies: Clinical
Presentation Number: 1201-264
- 2017 American College of Cardiology Foundation