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

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.

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.

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.

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.