New treatment options are now available for light-chain amyloidosis, with additional ones on the way, according to a presentation at the 21st Annual International Congress on Hematologic Malignancies.
New treatment options are now available for light-chain (AL) amyloidosis, with additional ones on the way, according to a presentation at the 21st Annual International Congress on Hematologic Malignancies, held February 23–25 in Sunny Isles, Florida.
“Treatment options are at work on two ends of the disease. New data show carfilzomib and daratumumab have activity in reducing production of clonal plasma cells. We also now have three antibodies that show activity in trials to dissolve amyloid deposits,” Morie Gertz, MD, professor of medicine at Mayo Clinic in Rochester, Minnesota, told Cancer Network.
AL amyloidosis is a rare disease, and early diagnosis is important to improve outcomes. However, “I continue to see patients in which oncologists have found monoclonal gammopathy of undetermined significance and don’t recognize that amyloidosis is present. They know it is not myeloma, but in reality, it is something worse. AL amyloidosis does not come to mind,” said Gertz.
The safety and efficacy of carfilzomib has been proven in previously treated systemic AL amyloidosis. Cardiac, pulmonary, and renal toxicities may be common, and N-terminal pro-B-type natriuretic peptide can increase in patients receiving carfilzomib, he said. “There has always been a concern of the possibility of cardiac toxicity with carfilzomib. The drug can be administered to AL amyloidosis patients safely, and produces benefits and responses. Carfilzomib has been established as a potential management, even if the patient’s heart is involved,” said Gertz.
With daratumumab, case reports show it clearly suppresses amyloid-producing plasma cells with minimal toxicity. Daratumumab trials are planned in the upfront setting, and it may produce significant benefits, he said.
Three antibodies are in production to treat amyloidosis. One attaches a glycoprotein to part of the matrix of amyloid deposits and has shown preliminary evidence of activity. Another antibody against amyloid epitope was found to be nontoxic, with no fusion reaction, and binds to amyloid deposits in a phase I safety study. A third attacks an epitope on amyloid and showed the ability to produce organ responses in a phase II study, with two phase III trials ongoing.
The default treatment for amyloidosis in the United States is bortezomib. “In our referral practice, bortezomib is the dominant agent in the nontransplant setting. A number of studies show a high response rate, and good depth of response,” said Gertz.
A combination of an alkylator and steroid is also a rational, reasonable treatment for AL amyloidosis. “It looks like response rates are slightly lower than with bortezomib, but there is not much toxicity, and we can give this combination to patients who have a build-up of cardiac, hepatic, or renal amyloid,” said Gertz.
His message to practicing oncologists is “keep the diagnosis of AL amyloidosis in mind to recognize it early on. We have a new promising application of bortezomib for this disease. Carfilzomib and daratumumab are also options for potential management of therapy. Antibodies are likely to advance the field in the near future,” said Gertz.
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