Journal of Clinical Oncology, Vol 10, 1696-1711, Copyright © 1992 by American Society of Clinical Oncology
Imaging, dosimetry, and radioimmunotherapy with iodine 131-labeled anti- CD37 antibody in B-cell lymphoma
MS Kaminski, LM Fig, KR Zasadny, KF Koral, RB DelRosario, IR Francis, CA Hanson, DP Normolle, E Mudgett and CP Liu
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109-0724.
PURPOSE: This study was undertaken to evaluate the tumor targeting,
toxicity, and therapeutic potential of the anti-B-cell-reactive monoclonal
antibody MB-1 (anti-CD37) labeled with iodine 131 given in a nonmarrow
ablative dose range in B-cell lymphoma patients who relapsed after
chemotherapy. PATIENTS AND METHODS: Twelve patients with MB-1- reactive
tumors were infused first with 40 mg of trace-labeled (3 to 7 mCi) MB-1.
Ten patients who had no serious toxicity postinfusion and who had
successful tumor imaging on serial gamma scans then received at least one
40-mg radioimmunotherapy (RIT) dose (25 to 161 mCi). Tracer estimates of
delivered whole-body dose (WBD) were used in prescribing a millicurie RIT
dose for seven patients. RESULTS: Eleven patients had positive tumor
imaging after a tracer dose, including patients with bulky tumors and/or
large tumor burdens (> or = 1 kg) +/- splenomegaly. However, overall
sensitivity for the detection of known tumor sites was only 39%. In six of
eight patients with dose-assessable tumors, the radiation dose to at least
one tumor was 1.1 to 3.1 times higher than to any normal organ, excluding
the spleen for a 40-mg tracer dose. Tracer-dose toxicities included
reversible glossal edema in one patient, grade 3 hepatic transaminasemia in
another, and early drops in both circulating B and T cells (with decreases
in B cells more pronounced) in nearly all patients. RIT toxicity was
primarily myelosuppression (especially thrombocytopenia), which had a
delayed onset and protracted recovery (without significant recovery until
at least 2 months post-RIT). Grade 3 myelosuppression in two of two
patients who were treated at a tracer-projected 50-cGy WBD level (133 and
149 mCi) precluded further planned RIT dose escalation. Less
myelosuppression was generally observed in patients who were treated at
< or = 40-cGy WBD levels. Antimouse antibodies developed in two
patients. Six patients had tumor responses post-RIT. Four had responses
that lasted more than 1 month (2 to 6 months), which included one complete
response, one partial response, one minor response, and one mixed response.
Responses seemed to occur more frequently in imaged tumors than in
nonimaged tumors. The most durable response occurred in a patient who had
the best antibody targeting to tumor. CONCLUSIONS: Although 131I-MB-1 has
limited diagnostic value, it can produce tumor responses at nonmarrow
ablative RIT doses. Further studies that focus on improving tumor targeting
with this or other B-cell-reactive radiolabeled antibodies and on
ameliorating the myelosuppression associated with the RIT-dosing approach
used in this trial are warranted.
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