A European collaborative study of treatment outcomes in 346 patients with cardiac stage III AL amyloidosis
ABSTRACT Treatment outcomes of patients with cardiac stage III light chain (AL) amyloidosis remain poorly studied. Such cases have been excluded from most clinical studies due to perceived dismal prognosis. We report treatment outcomes of 346 patients with stage III AL amyloidosis from the United Kingdom, Italy, Germany, and Greece. Median overall survival (OS) was 7 months with OS at 3, 6, 12, and 24 months of 73%, 55%, 46%, and 29%, respectively; 42% died before first response evaluation. On an intention-to-treat basis, the overall hematologic response rate was 33%, including a complete response rate of 12%. OS rates at 12 and 24 months, respectively, for 201 response evaluable patients were 88% and 85% for complete responders, 74% and 53% for partial responders, and 39% and 22% for nonresponders. Forty-five percent of responders achieved an organ response. Amino-terminal fragment of brain-type natriuretic peptide (NT-proBNP) >8500 ng/L and systolic blood pressure (SBP) <100 mm Hg were the only factors that independently impacted OS and identified an especially poor prognosis subgroup of patients with a median OS of only 3 months. Outcome and organ function of stage III AL amyloidosis without very elevated NT-proBNP and low SBP is improved by a very good hematologic response to chemotherapy.
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ABSTRACT: AL amyloidosis patients with multi-organ and particularly cardiac involvement have historically been considered to have a bad prognosis. The introduction of autologous stem cell transplantation was associated with unacceptable toxicity in high-risk patients, but responding patients have prolonged overall survival. Toxicities can be decreased by careful patient selection, but this reduces the applicability of this treatment modality to a limited number of patients. Efforts are therefore needed to design novel more effective regimens, with the use of new medications, such as thalidomide, lenalidomide and bortezomib, next generation immunomodulatory drugs and proteasome inhibitors. Their combination with dexamethasone and alkylating agents show promising results, allowing a high percentage of remission and subsequent event-free and overall survival, even in a significant proportion of high risk, poor prognosis populations. This review includes the state-of-the-art treatment for AL amyloidosis patients as of 2012, in light of the progress in management of this disease during recent years.British Journal of Haematology 01/2013; 160(5). DOI:10.1111/bjh.12191 · 4.96 Impact Factor
- Blood 04/2013; 121(17):3301-2. DOI:10.1182/blood-2013-03-491746 · 10.43 Impact Factor
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ABSTRACT: AL amyloidosis is caused by a small, indolent plasma cell clone synthesizing light chains that misfold and cause devastating damage of vital organs. Early diagnosis, before development of advanced cardiomyopathy, is the key to improving outcomes. This makes prompt recognition of "red-flags" crucial to trigger appropriate diagnostic procedures. Differentiation from other diagnoses, especially other systemic amyloidoses, may be challenging and may require advanced technologies. Prognosis is heavily dependent on the extent of cardiac involvement, and cardiac biomarkers should guide the choice of therapy. Treatment for AL amyloidosis is highly individualized due to the protean clinical presentation. Close monitoring of clonal and organ response guides regimen changes and duration of therapy. Alkylator-based chemotherapy, either conventional or high-dose, is effective in almost two thirds of patients. The combinations of proteasome inhibitors with dexamethasone and alkylators are feasible in most patients achieving high response rates although there is a need for controlled studies. Risk-adapted stem cell transplant and consolidation with novel agents may be considered in selected patients. The immune-modulatory drugs have an important role in treatment of refractory/relapsed patients. Novel agents and therapeutic targets are expected to be exploited, in the framework of an integrated, more effective and less toxic treatment strategy.Blood 05/2013; DOI:10.1182/blood-2013-01-453001 · 10.43 Impact Factor