IDEC-Y2B8 Radioimmunotherapy: Baseline Bone Marrow Involvement and Platelet Count Are Better Predictors of Hematologic Toxicity Than Dosimetry
Clinical trials with yttrium-90 and iodine-131 radioimmunotherapy have demonstrated efficacy in the treatment of non-
Clinical trials with yttrium-90 and iodine-131 radioimmunotherapy have demonstrated efficacy in the treatment of non-Hodgkins lymphoma (NHL). Dosimetry has been included as a safety measure prior to therapy and is necessary for therapeutic dose calculations with some iodine-131labeled antibodies. The relative advantages of these two isotopes have been debated. The use of yttrium-90 may have an advantage over iodine-131 in the treatment of bulky or poorly vascularized tumors. As a pure, high-energy, beta-emitting isotope, yttrium-90 can deliver more energy to the tumor than iodine-131 (2.3 MeV for yttrium-90 vs 0.81 MeV for iodine-131) and has a longer path length (5-10 mm vs 1-2 mm) that may allow tumor cells in the vicinity of the antibody-bound tumor cell to be killed without direct antibody binding.
A phase I/II study was performed with IDEC-Y2B8, a yttrium-90labeled murine anti-CD20 IgG kappa monoclonal antibody that targets over 90% of B-cell NHLs. Fifty-eight relapsed or refractory NHL patients (6% small lymphocytic, 65% follicular, 24% diffuse large cell [DLC] and diffuse mixed cell [DMC], 6% mantle cell) underwent imaging and dosimetry with indium-111 labeled antibody (IDEC-In2B8) 1 week prior to therapy. Rituximab (Rituxan; 250 mg/m²) was given prior to both imaging and therapeutic radiolabeled antibodies. Treatment was given to 50 group 2 and 3 patients as an outpatient single dose of 0.2, 0.3, or 0.4 mCi/kg. Phase II doses of 0.4 and 0.3 mCi/kg were chosen for patients with mild thrombocytopenia (platelets, 100,000-150,000/mm³).
Analysis of bone marrow dosimetry (including whole-blood half-life and AUC, blood- and sacral-derived bone marrow dosimetry) vs grade hematologic toxicity for phase II patients given 0.4 or 0.3 mCi/kg did not demonstrate a significant correlation. A significant correlation was demonstrated, however, between degree of bone marrow involvement with lymphoma and incidence of grade 4 (platelets, £ 25,000/mm³; ANC, £ 500/mm³) nadir. Grade 4 thrombocytopenia developed in 8% (2/25) of patients without marrow involvement vs 25% (1/4) of those with 0.1%-5% involvement, 45% (5/11) of those with 5%-20% involvement, and 100% (6/6) of those with 20%-25% involvement. Overall, only 5 (10%) patients developed platelet counts <10,000/mm³.
CONCLUSION: These phase I/II results suggest that clinical parameters, including baseline platelet count and degree of bone marrow involvement with lymphoma, may be able to replace dosimetry for safe administration of IDEC-Y2B8 in patients with NHL. Hematologic toxicity of IDEC-Y2B8 is clearly related to therapeutic antibody targeting of lymphoma cells residing in marrow.
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