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New drug therapy of amyloidoses: resorption of AL-type deposits with 4'-iodo-4'-deoxydoxorubicin.
Blood 1995 August 2
Amyloidosis caused by monoclonal Ig light chains (AL) is characterized by the tissue deposition of paraproteins as insoluble fibrils that leads to organ dysfunction and death. After serendipitous observation of its efficacy, the new anthracycline 4'-iodo-4'-deoxydoxorubicin (I-DOX) was evaluated in eight patients with biopsy-proven AL and symptomatic organ involvement who received 1 to 6 administrations of I-DOX at dosages of 15 to 100 mg/m2. Five patients showed substantial clinical improvement concomitant with instrumental and physical evidence of response, and three patients presented objective evidence of amyloid resorption. The effects of I-DOX on amyloid deposits were not associated with cytotoxicity to the amyloidogenic clone. Five patients died of disease-related complications at 4 to 36 months; the remaining three are alive 29, 35, and 44 months after starting treatment. I-DOX caused short-lived granulocytopenia and minimal extra-hematologic side effects. The pharmacokinetics of I-DOX presented features exploitable for diagnosis in amyloidotic patients and documented the active metabolite in the cerebrospinal fluid. We conclude that I-DOX represents an important treatment option for subjects with AL amyloidosis and could be the prototype of a new class of drugs that interfere with and reverse the process of all types of amyloid deposition.
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