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New drug therapy of amyloidoses: resorption of AL-type deposits with 4'-
iodo-4'-deoxydoxorubicin
L Gianni, V Bellotti, AM Gianni and G Merlini
Division of Medical Oncology, Istituto Nazionale Tumori, Milan.
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.
Volume 86,
Issue 3,
pp. 855-861,
08/01/1995
Copyright © 1995 by The American Society of Hematology
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