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Ibritumomab Tiuxetan Radioimmunotherapy of Rituximab-Refractory Follicular Non-Hodgkin’s Lymphoma

Ibritumomab Tiuxetan Radioimmunotherapy of Rituximab-Refractory Follicular Non-Hodgkin’s Lymphoma

Ibritumomab tiuxetan (Zevalin) is an anti-CD20 murine IgG1 kappa monoclonal antibody covalently bound to tiuxetan, which forms a strong chelate with the pure beta-emitting isotope yttrium-90. We conducted an open-label trial of ibritumomab tiuxetan in 54 follicular non-Hodgkin’s lymphoma (NHL) patients refractory to rituximab (ie, nonresponders or patients with a time to progression [TTP] of less than 6 months after rituximab at 375 mg/m2 weekly × 4). Efficacy end points included objective response rate (ORR), duration of response (DR), TTP, and comparison of ORR and DR to that achieved with prior rituximab and prior chemotherapy. Patients were excluded if they had more than 25% bone marrow involvement with NHL, more than 5,000 circulating lymphocytes, prior autologous bone marrow transplant/peripheral blood stem cell transplant, or prior radioimmunotherapy.

Patient characteristics included a median age of 54 years; follicular histology (95% of patients); a median of four prior therapies; bone marrow involvement (32% of patients); splenomegaly (12% of patients); bulky disease (5 cm [74% of patients], 7 cm [44%], 10 cm [19%]); prior radiotherapy (30%); International Prognostic Index intermediate/high or high risk (19%). All patients who underwent dosimetry had acceptable biodistribution and estimated radiation absorbed doses to normal organs.

Toxicity was primarily hematologic, transient, and reversible. Median hematologic nadirs were absolute granulocyte count 700 cells/µL and platelets 33,000/µL. Transient grade 4 thrombocytopenia and neutropenia occurred in 9% and 35%, respectively. Median time to recovery for patients with nadirs under absolute neutrophil count 1,000 cells/µL or platelets 50,000/µL were 8 and 13 days, respectively. Infections requiring hospitalization occurred in 7%.

Response classification was assigned by a Lymphoma Expert Confirmation of Response (LEXCOR) panel that was blinded to investigator designation of response. Objective response rates using the International Workshop NHL response criteria (J Clin Oncol 17[4]:1244-1253, 1999) were ORR 74% and CR 15% for follicular patients. Using IDEC protocol-defined criteria, ORR was 59% and CR was 4%. The median TTP has not been reached. The Kaplan-Meier (KM) estimate is 7.5+ months (95% confidence interval [CI] = 6.3 to 9.1 months). The KM estimate of DR is 7.7+ months [95% CI: 5.5 to 8.4 months)], with 50% of patients still censored. Duration of response estimates were significantly longer (7.7+ vs 4 months) for ibritumomab tiuxetan as compared to prior rituximab (P < .001). The KM estimate of DR for ibritumomab tiuxetan (median: fifth treatment regimen) was 7.7+ months, and that for prior chemotherapy (median: third treatment regimen) was 6.5 months.

CONCLUSION: Ibritumomab tiuxetan radioimmunotherapy is safe and effective in the treatment of rituximab-refractory follicular NHL.

Click here to read Dr. Bruce Cheson's commentary on this abstract.

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