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 (Zevalin) is an anti-CD20 murineIgG1 kappamonoclonal antibody covalently bound to tiuxetan, which forms a strong chelatewith the pure beta-emitting isotope yttrium-90. We conducted an open-label trialof ibritumomab tiuxetan in 54 follicular non-Hodgkin’s lymphoma (NHL) patientsrefractory to rituximab (ie, nonresponders or patients with a time toprogression [TTP] of less than 6 months after rituximab at 375 mg/m2 weekly ×4). Efficacy end points included objective response rate (ORR), duration ofresponse (DR), TTP, and comparison of ORR and DR to that achieved with priorrituximab and prior chemotherapy. Patients were excluded if they had more than25% 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; bonemarrow involvement (32% of patients); splenomegaly (12% of patients); bulkydisease (5 cm [74% of patients], 7 cm [44%], 10 cm [19%]); prior radiotherapy(30%); International Prognostic Index intermediate/high or high risk (19%). Allpatients who underwent dosimetry had acceptable biodistribution and estimatedradiation absorbed doses to normal organs.
Toxicity was primarily hematologic, transient, and reversible.Median hematologic nadirs were absolute granulocyte count 700 cells/µL andplatelets 33,000/µL. Transient grade 4 thrombocytopenia and neutropeniaoccurred in 9% and 35%, respectively. Median time to recovery for patients withnadirs under absolute neutrophil count 1,000 cells/µL or platelets 50,000/µLwere 8 and 13 days, respectively. Infections requiring hospitalization occurredin 7%.
Response classification was assigned by a Lymphoma ExpertConfirmation of Response (LEXCOR) panel that was blinded to investigatordesignation of response. Objective response rates using the InternationalWorkshop 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, ORRwas 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% ofpatients still censored. Duration of response estimates were significantlylonger (7.7+ vs 4 months) for ibritumomab tiuxetan as compared to priorrituximab (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 andeffective in the treatment of rituximab-refractory follicular NHL.
Click here to read Dr. Bruce Cheson's commentary on this abstract.
