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

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OncologyONCOLOGY Vol 14 No 3
Volume 14
Issue 3

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-Hodgkin’s 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 Cheson’s commentary on this abstract.

Articles in this issue

Comparative Economic Analysis of the Treatment of Relapsed Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) in France Using CHOP, Fludarabine, or Rituximab
FHIT Gene, Smoking, and Cervical Cancer
Final Report on the Safety and Efficacy of Retreatment With Rituximab for Patients With Non-Hodgkins Lymphoma
Prospective, Randomized, Controlled Study of Zevalin Radioimmunotherapy Compared to Rituximab Immunotherapy for B-Cell, Non-Hodgkins Lymphoma: Interim Results
IOM Medical Error Estimates Questioned, But Legislation Considered
Less Toxic Therapies for Hodgkin’s Disease May Reduce Secondary Cancers
Preserving Fertility in Young Women With Ovarian Cancer Does Not Decrease Survival
Iodine-131 Tositumomab for Patients With Transformed, Low-Grade Non-Hodgkin’s Lymphoma: Overall Clinical Trial Experience
Survival Rates Significantly Worse For African-Americans With Endometrial Cancer
Rituximab Has Significant Activity in Patients With Chronic Lymphocytic Leukemia
Responders to Rituximab Show Continued Tumor Regression Over Time and a Progression-Free Survival That Correlates With Response Classification
PhRMA Criticizes FDA’s Proposed Rule on Antibiotic Approvals
Phase II Study of Rituximab in Combination With CHOP in Patients With Previously Untreated Intermediate- or High-Grade Non-Hodgkin’s Lymphoma
New Antibiotic Effective in Treating Gram-Positive Bacteremia
Reduced-Dose Zevalin Radioimmunotherapy for Relapsed or Refractory B-Cell Non-Hodgkin&#146;s Lymphoma Patients With Preexisting Thrombocytopenia: Report of Interim Results of a Phase II Trial
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