Tositumomab and (131)I therapy in non-Hodgkin's lymphoma

Abstract

Tositumomab and (131)I-tositumomab constitute a relatively new radioimmunotherapeutic regimen for patients with CD20+ follicular non-Hodgkin's lymphoma (NHL). Currently, it is approved for use in patients whose disease has relapsed after chemotherapy and is refactory to rituximab, including patients whose tumors have transformed to a higher histologic grade. This review outlines the current and evolving status of this therapeutic regimen at nonmyeloablative doses.

Methods: Clinical data from multiple published studies and preliminary communications encompassing more than 1,000 patients were reviewed to describe the current status of tositumomab and (131)I-tositumomab therapy. The therapy is delivered in 2 parts, a dosimetric dose and a therapeutic dose. The therapeutic radioactivity millicurie dose is calculated on a patient-individualized ("tailored") basis. A series of 3 total-body gamma-camera scans are used to determine the patient-specific pharmacokinetics (total-body residence time) of the radiolabeled antibody conjugate required to deliver the desired total-body radiation dose, typically 75 cGy.

Results: In clinical trials, objective response rates in patients who had been extensively pretreated with chemotherapy ranged from 47% to 68%. Tositumomab and (131)I-tositumomab therapy also was effective in patients who had failed to respond to or who had relapsed after rituximab therapy, with a 68% overall response rate. Thirty percent of such patients achieved complete responses that were generally of several years duration. Single-center trials using tositumomab and (131)I-tositumomab therapy alone or after chemotherapy in previously untreated patients have shown response rates in excess of 90%, with most responses complete. Retreatment with tositumomab and (131)I-tositumomab and use of lower total-body radiation doses of tositumomab and (131)I-tositumomab to treat patients who have relapsed after stem cell transplantation have been shown feasible in limited clinical studies. Toxicity is predominately hematologic; however, human antimouse antibodies, hypothyroidism, and myelodysplastic syndrome have been reported in a small fraction of patients.

Conclusion: Tositumomab and (131)I-tositumomab therapy at patient-specific, nonmyeloablative doses is safe and effective in treatment of relapsed and refractory follicular NHL. Toxicity is mainly hematologic and reversible. Tositumomab and (131)I-tositumomab therapy is assuming a growing role in this common malignancy.