Phase I study of the pharmacokinetics of a radioimmunoconjugate, 90Y-T101, in patients with CD5-expressing leukemia and lymphoma.
Ten patients with advanced or refractory CD5-expressing hematologic neoplasms [two with chronic lymphocytic leukemia and eight with cutaneous T-cell lymphoma (CTCL)] were treated in a Phase I study with the radioimmunoconjugate 90Y-T101, which targets CD5+ lymphocytes. Prior imaging studies using 111In-T101 demonstrated uptake in involved lymph nodes and skin in patients with CTCL, and Phase I studies with unmodified T101 demonstrated transient responses. In this study, patients were treated with 5 or 10 mCi of 90Y chelated to T101 via isothiocyanatobenzyl diethylenetriamine pentaacetic acid, along with tracer doses of 111In-T101 for imaging. The biodistribution of the radioimmunoconjugate was determined by measuring 90Y and 111In blood clearance, urine excretion, and accumulation in bone marrow and in involved skin lesions. The intravascular pharmacokinetics of 90Y were predicted by 111In-labeled T101. The greatest differences in biodistribution between 111In and 90Y were in the higher bone accumulation of 90Y and its lower urinary excretion. Imaging studies demonstrated targeting of skin lesions and involved lymph nodes in CTCL patients. The predominant toxicity was bone marrow suppression. Rapid antigenic modulation of CD5 on circulating T and B cells was observed. Recovery of T-cell populations occurred within 2-3 weeks; however, suppression of B-cell populations persisted after 5+ weeks. All CTCL patients developed human antimouse antibody after one cycle and thus were not retreated; one patient with chronic lymphocytic leukemia received a second cycle of therapy. Partial responses occurred in five patients, two with chronic lymphocytic leukemia and three with CTCL. The median response duration was 23 weeks. One CTCL patient who subsequently received electron beam irradiation to a residual lesion is disease-free after 6 years.
Foss
F M
FM
National Cancer Institute Navy Medical Oncology Branch, National Cancer Institute, Bethesda, Maryland 20889, USA.
Raubitscheck
A
A
Mulshine
J L
JL
Fleisher
T A
TA
Reynolds
J C
JC
Paik
C H
CH
Neumann
R D
RD
Boland
C
C
Perentesis
P
P
Brown
M R
MR
Frincke
J M
JM
Lollo
C P
CP
Larson
S M
SM
Carrasquillo
J A
JA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use; D018956:CD5 Antigens / Q000276:immunology*; D006801:Humans; D018796:Immunoconjugates / Q000009:adverse effects / Q000276:immunology / Q000493:pharmacokinetics* / Q000627:therapeutic use; D007205:Indium Radioisotopes / Q000493:pharmacokinetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000276:immunology / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy; D016131:Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology; D016410:Lymphoma, T-Cell, Cutaneous / Q000276:immunology / Q000378:metabolism* / Q000532:radiotherapy / Q000628:therapy; D008875:Middle Aged; D016499:Radioimmunotherapy; D014018:Tissue Distribution; D016896:Treatment Outcome; D015021:Yttrium Radioisotopes / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000627:therapeutic use
D000911:Antibodies, Monoclonal; D018956:CD5 Antigens; D018796:Immunoconjugates; D007205:Indium Radioisotopes; D015021:Yttrium Radioisotopes