IDEC-Y2B8 Radioimmunotherapy: Baseline Bone Marrow Involvement and Platelet Count Are Better Predictors of Hematologic Toxicity Than Dosimetry

OncologyONCOLOGY Vol 13 No 3
Volume 13
Issue 3

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-Hodgkin’s lymphoma (NHL). Dosimetry has been included as a safety measure prior to therapy and is necessary for therapeutic dose calculations with some iodine-131–labeled 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-90–labeled 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.

Click here for Dr. Bruce Cheson’s commentary on this abstract.

Articles in this issue

WHO Declares Lymphatic Mapping to Be the Standard of Care for Melanoma
Rituximab: Phase II Retreatment Study in Patients With Low-Grade or Follicular Non-Hodgkin’s Lymphoma
Response Criteria for NHL: Importance of “Normal” Lymph Node Size and Correlations With Response
Chemotherapy Plus Radiation Improves Survival in Patients With Cervical Cancer
A Randomized Trial of Fludarabine, Mitoxantrone (FM) Versus Doxorubicin, Cyclophosphamide, Vindesine, Prednisone (CHEP) as First Line Treatment in Patients With Advanced Low-Grade Non-Hodgkin's Lymphoma: A Multicenter Study by GOELAMS Group
Navelbine Increased Elderly Lung Cancer Patients’ Survival
Fludarabine Versus Conventional CVP Chemotherapy in Newly C Diagnosed Patients With Stages III and IV Low-Grade Malignant Non-Hodgkin’s Lymphoma: Preliminary Results From a Prospective, Randomized Phase III Clinical Trial in 381 Patients
Multicenter, Phase III Study of Iodine-131 Tositumomab (Anti-B1 Antibody) for Chemotherapy-Refractory Low-Grade or Transformed Low-Grade Non-Hodgkin’s Lymphoma
T-Cell–Depleted Allogeneic Bone Marrow Transplant From HLA-Matched Sibling Donors for Non-Hodgkin’s Lymphoma
Consensus Statement on Prevention and Early Diagnosis of Lung Cancer
In Vivo Purging and Adjuvant Immunotherapy With Rituximab During PBSC Transplant For NHL
Fludarabine and Cyclophosphamide: A Highly Active and Well-Tolerated Regimen for Patients With Previously Untreated Indolent Lymphomas
Campath-1H Monoclonal Antibody in Therapy for Advanced Low-Grade Non-Hodgkin’s Lymphomas: A Phase II Study
AIDS Drugs Effective Against Most Common HIV Strain
Rituximab Therapy in Previously Treated Waldenström’s Macroglobulinemia: Preliminary Evidence of Activity
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