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Effects of monoclonal antibody therapy in patients with chronic lymphocytic
leukemia
KA Foon, RW Schroff, PA Bunn, D Mayer, PG Abrams, M Fer, J Ochs, GC Bottino, SA Sherwin and DJ Carlo
A phase I clinical trial was initiated to treat patients with stage IV
B-derived chronic lymphocytic leukemia (CLL) with the IgG2a murine
monoclonal antibody T101. This antibody binds to a 65,000-mol wt (T65)
antigen found on normal T lymphocytes, malignant T lymphocytes, and B-
derived CLL cells. All of the patients had a histologically confirmed
diagnosis of advanced B-derived CLL and were refractory to standard
therapy, and more than 50% of their leukemia cells reacted with the T101
antibody in vitro. The patients received T101 antibody two times per week,
over two to 50 hours by intravenous administration in 100 mL of normal
saline containing 5% human albumin. Twelve patients were treated with a
fixed dosage of 1, 10, 50, or 100 mg, and one patient was treated with 140
mg of antibody. It was demonstrated that patients given two-hour infusions
of 50 mg developed pulmonary toxicity, with shortness of breath and chest
tightness. This toxicity was eliminated when infusions of 50 or 100 mg of
T101 were prolonged to 50 hours. All dose levels caused a rapid but
transient decrease in circulating leukemia cell counts. In vivo binding to
circulating and bone marrow leukemia cells was demonstrated at all dose
levels with increased binding at higher dosages. Antimurine antibody
responses were not demonstrated in any patients at any time during
treatment. Circulating free murine antibody was demonstrated in the serum
of only the two patients treated with 100 mg of antibody as a 50-hour
infusion and the patient treated with 140 mg of antibody over 30 hours.
Antigenic modulation was demonstrated in patients treated at all dose
levels but was particularly apparent in patients treated with prolonged
infusions of 50 and 100 mg of antibody. We were also able to demonstrate
antigenic modulation in lymph node cells, which strongly suggests in vivo
labeling of these cells. Overall, T101 antibody alone appears to have a
very limited therapeutic value for patients with CLL. The observations of
in vivo labeling of tumor cells, antigenic modulation, antibody
pharmacokinetics, toxicity, and antimurine antibody formation may be used
in the future for more effective therapy when drugs or toxins are
conjugated to the antibody.
Volume 64,
Issue 5,
pp. 1085-1093,
11/01/1984
Copyright © 1984 by The American Society of Hematology
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