ANTIIDIOTYPE ANTIBODIES CAN INDUCE LONG-TERM COMPLETE REMISSIONS IN NON-HODGKINS-LYMPHOMA WITHOUT ERADICATING THE MALIGNANT CLONE

The immunoglobulin on the surface of B-cell lymphomas can be a turner- specific target for monoclonal antibody therapy. Between 1981 and 1993 , 45 individuals with low grade B-cell lymphoma were treated with 52 c ourses of custom-made anti-idiotype antibodies. The antibodies were us ed either alone or in combination with alpha-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 pati ents (13%) experienced prolonged complete remissions, five of which ar e 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 pa tients with prolonged remissions. We performed enzyme-linked immunosor bent assay (ELISA) assays for idiotype protein or anti-idiotype antibo dies in serum. Blood and bone marrow samples were examined by flow cyt ometry for idiotype positive cells, and by polymerase chain reaction ( PCR) for clonal gene rearrangements of immunoglobulin CDR3 sequences o r t(14;18) translocations, Using these sensitive and specific tests it was possible to detect very low levels of residual lymphoma in five o f these patients who had been in clinical remission for 3 to 8 years b efore this evaluation. These five have continued without recurrence fo r up to 3 years since. Thus, we have found a pattern of residual inact ive disease in patients treated with anti-idiotype antibodies. The bio logy 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 mal ignant clone. (C) 1998 by The American Society of Hematology.