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Blood, Vol. 92 No. 4 (August 15), 1998:
pp. 1184-1190
Anti-Idiotype Antibodies Can Induce Long-Term Complete Remissions
in Non-Hodgkin's Lymphoma Without Eradicating the Malignant Clone
Thomas A. Davis,
David G. Maloney,
Debra K. Czerwinski,
Tina-Marie Liles, and
Ronald Levy
From the Division of Medical Oncology, Stanford University School of
Medicine, Stanford, CA; and the Fred Hutchinson Cancer Center,
University of Washington, Seattle, WA.
The immunoglobulin on the surface of B-cell lymphomas can be a
tumor-specific target for monoclonal antibody therapy. Between 1981 and
1993, 45 individuals with low grade B-cell lymphoma were treated with
52 courses of custom-made anti-idiotype antibodies. The antibodies were
used either alone or in combination with  -interferon, chlorambucil,
or interleukin-2 (IL-2). The majority of these patients responded to
treatment, with a 66% overall and 18% complete response rate. Six
patients (13%) experienced prolonged complete remissions, five of
which are ongoing from 4 to 10 years after therapy and are the subject
of this report. We asked whether residual lymphoma could be found in
these patients with prolonged remissions. We performed enzyme-linked
immunosorbent assay (ELISA) assays for idiotype protein or
anti-idiotype antibodies in serum. Blood and bone marrow samples were
examined by flow cytometry for idiotype positive cells, and by
polymerase chain reaction (PCR) for clonal gene rearrangements of
immunoglobulin CDR3 sequences or t(14;18) translocations. Using these
sensitive and specific tests it was possible to detect very low levels
of residual lymphoma in five of these patients who had been in clinical
remission for 3 to 8 years before this evaluation. These five have
continued without recurrence for up to 3 years since. Thus, we have
found a pattern of residual inactive disease in patients treated with
anti-idiotype antibodies. The biology of follicular lymphoma evidently
includes the potential for tumor dormancy after therapies with varied
mechanisms of action, resulting in clinical inactivity for many years.
Thus, long-term control of the disease is possible at a clinical level despite persistence of the malignant clone.
© 1998 by The American Society of Hematology.
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