PHASE-I STUDY OF THE PHARMACOKINETICS OF A RADIOIMMUNOCONJUGATE, Y-90T101, IN PATIENTS WITH CD5-EXPRESSING LEUKEMIA AND LYMPHOMA

Ten patients with advanced or refractory CDS-expressing hematologic ne oplasms [two with chronic lymphocytic leukemia and eight with cutaneou s T-cell lymphoma (CTCL)] were treated in a Phase I study with the rad ioimmunoconjugate Y-90-T101, which targets CD5+ lymphocytes, Prior ima ging studies using In-111-T101 demonstrated uptake in involved lymph n odes and skin in patients with CTCL, and Phase I studies with unmodifi ed T101 demonstrated transient responses. In this study, patients were treated with 5 or 10 mCi of Y-90 chelated to T101 via isothiocyanatob enzyl diethylenetriamine pentaacetic acid, along with tracer doses of In-111-T101 for imaging. The biodistribution of the radioimmunoconjuga te was determined by measuring Y-90 and In-111 blood clearance, urine excretion, and accumulation in bone marrow and in involved skin lesion s. The intravascular pharmacokinetics of Y-90 were predicted by In-111 -labeled T101, The greatest differences in biodistribution between ''' In and 90Y were in the higher bone accumulation of 90Y and its lower u rinary excretion. Imaging studies demonstrated targeting of skin lesio ns and involved lymph nodes in CTCL patients. The predominant toxicity was bone marrow suppression. Rapid antigenic modulation of CD5 on cir culating T and B cells was observed. Recovery of T-cell populations oc curred within 2-3 weeks; however, suppression of B-cell populations pe rsisted after 5+ weeks, All CTCL patients developed human antimouse an tibody after one cycle and thus were not retreated; one patient with c hronic lymphocytic leukemia received a second cycle of therapy. Partia l responses occurred in five patients, two with chronic lymphocytic le ukemia 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.