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A clinical trial of anti-idiotype therapy for B cell malignancy
TC Meeker, J Lowder, DG Maloney, RA Miller, K Thielemans, R Warnke and R Levy
Eleven patients with B lymphocytic malignancy were treated with mouse
monoclonal anti-idiotype antibodies. All but one of the patients in this
study had received extensive prior treatment with conventional lymphoma
therapy. All antibodies were prepared against, and uniquely reactive with,
the patient's own tumor. Ten patients were treated with a single antibody,
but one patient received three antibodies concurrently. The treatment
protocol initially used an escalating dose schedule that was intended to
evaluate toxicity, pharmacokinetics and, eventually, to achieve appreciable
levels of free mouse antibody in the circulation. The last two patients
received substantial initial doses. Tumor sampling was performed before and
during therapy to evaluate tissue penetration by antibody. None of the
patients had serum paraproteins by routine clinical testing, but six had
idiotype protein detectable by a sensitive immunoassay at levels greater
than 1 microgram/mL, two of which were greater than 200 micrograms/mL.
Plasmapheresis was capable of reducing these levels temporarily. However,
the presence of serum idiotype increased the requirement for mouse antibody
to achieve tumor penetration. Another obstacle to treatment was immune
response to mouse Ig, which occurred in five of the 11 patients. Once an
immune response had begun, further infusions of antibody were not capable
of reaching the tumor or inducing tumor regression and were associated with
toxicity. Our initial patient remains in an unmaintained complete remission
42 months after receiving antibody. Five of ten additional patients have
had objective remissions that were also clinically significant. However,
these remissions were not complete and were of relatively short duration.
This therapy shows promise as an alternative modality for the treatment of
B cell malignancy. Further study will be needed to determine the mechanisms
of the antitumor effect and to improve the clinical results.
Volume 65,
Issue 6,
pp. 1349-1363,
06/01/1985
Copyright © 1985 by The American Society of Hematology
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