Reduced-Dose Zevalin Radioimmunotherapy for Relapsed or Refractory B-Cell Non-Hodgkin’s Lymphoma Patients With Preexisting Thrombocytopenia: Report of Interim Results of a Phase II Trial
Ibritumomab tiuxetan (IDEC-Y2B8 [Zevalin]) is an anti-CD20 murine immunoglobulin G1 (IgG1) kappa monoclonal antibody conjugated to tiuxetan that can securely chelate either indium-111 (111In) for imaging/dosimetry or yttrium-90 (90Y) for
Ibritumomab tiuxetan (IDEC-Y2B8 [Zevalin]) is an anti-CD20 murine immunoglobulin G1 (IgG1) kappa monoclonal antibody conjugated to tiuxetan that can securely chelate either indium-111 (111In) for imaging/dosimetry or yttrium-90 (90Y) for therapy. Phase I/II trials (J Clin Oncol 17[12]:3793-3803, 1999) demonstrated that the clinical parameters of baseline platelet count and percentage involvement of bone marrow with non-Hodgkins lymphoma (NHL) were correlated with the severity of hematologic toxicity, while bone marrow dosimetry was not. The maximum tolerated dose was found to be 0.4 mCi/kg (0.3 mCi/kg in patients with mild thrombocytopenia).
Based on these data, we conducted a phase II trial to further evaluate the safety and efficacy of 0.3 mCi/kg of 90Y-labeled tiuxetan for the treatment of patients with relapsed or refractory, low-grade, follicular, or transformed CD20-positive B-cell NHL. Patients with < 25% bone marrow involvement (on bone marrow biopsy), no prior radioimmunotherapy, circulating lymphocytes < 5,000 cells/mm³, an absolute neutrophil count (ANC) ³ 1,500 cells/mm³, platelet counts between 100,000 and 149,000 cells/mm³ and no prior autologous bone marrow transplantation (BMT) or stem-cell therapy were eligible. Accrual is now complete at 30 patients.
An interim analysis was performed on the first 24 patients. Their characteristics were: median age, 61 years (25% ³ 75 years); and 42% were female. A total of 83% of patients had follicular histology; 13%, transformed NHL; and 4%, small lymphocytic or lymphoplasmacytic NHL. Almost half of the patients (46%) had bulky disease ³ 5 cm; 21% had bulky disease > 7 cm; 13% had bulky disease ³ 10 cm; and 25% had splenomegaly. All 30 patients (100%) had received prior chemotherapy (median prior therapies, two); 13% had undergone prior radiotherapy; and 4% had received prior bioimmunotherapy.
All patients underwent imaging and dosimetry with 111In-labeled tiuxetan. In all cases, biodistribution and dosimetry were acceptable. (Protocol-defined limits for the estimated absorbed radiation dose were < 2,000 cGy to normal organs and < 300 cGy to bone marrow).
Toxicity was primarily hematologic, transient, and reversible. Median nadirs for patients receiving 0.3 mCi/kg (maximum dose, 32 mCi) were an ANC of 600 cells/mm³ platelets, 34,000 cells/mm³; and hemoglobin, 10.0 g/dL. Grade 4 neutropenia and thrombocytopenia occurred in 25% and 15% of these patients, respectively.
The overall response rate was 68% (23% complete responses [CRs]; 45% partial responses [PRs]) in the 22 patients for whom response assessment was available.
CONCLUSION: Patients with relapsed or refractory, low-grade, follicular, or transformed, CD20-positive B-cell NHL with mild thrombocytopenia can be safely treated with reduced-dose (0.3-mCi/kg) tiuxetan with an excellent clinical response.
Click here for Dr. Bruce Chesons commentary on this abstract.
Highlighting Insights From the Marginal Zone Lymphoma Workshop
Clinicians outline the significance of the MZL Workshop, where a gathering of international experts in the field discussed updates in the disease state.
