Tositumomab

(rINN)
Synonyms: B-1; Tositumomabum. Immunoglobulin G2a anti-(human antigen CD 20) (mouse monoclonal clone B1R1 with mouse monoclonal clone B1R1 x -chain, dimer.
Cyrillic synonym: Тоситумомаб.

💊 Chemical information

CAS — 192391-48-3.

💊 Adverse Effects, Treatment, and Precautions

Infusion reactions suggestive of a cytokine release syndrome, and other hypersensitivity reactions including anaphylaxis, have been reported with tositumomab. Prolonged and severe neutropenia, thrombocytopenia, and anaemia occur commonly; full blood counts should be monitored weekly for up to 12 weeks. Other adverse effects include gastrointestinal disturbances, dehydration, abdominal pain, pleural effusion, and increased susceptibility to infection. Delayed adverse effects such as the development of secondary malignancies, leukaemia, or myelodysplastic syndrome may occur. Patients receiving the radiolabelled regimen may be susceptible to hypothyroidism and pretreatment with thyroid blocking drugs is recommended (see Uses and Administration, below); levels of thyroid-stimulating hormone should be measured before treatment and annually thereafter.

💊 Uses and Administration

Tositumomab is an anti-B1 monoclonal antibody that is directed against the CD20 antigen found on the surface of B lymphocytes. It is radiolabelled with iodine-131 for the treatment of patients with CD20 antigen-expressing, relapsed or refractory, low-grade, follicular, or transformed non-Hodgkin’s lymphoma, and including those patients who have disease refractory to rituximab. The regimen consists of a dosimetric step, followed 7 to 14 days later by a therapeutic step. The dosimetric step consists of 450 mg of tositumomab given intravenously in 50 mL sodium chloride 0.9% over 60 minutes. Tositumomab 35 mg radiolabelled with iodine-131 is then given intravenously in 30 mL sodium chloride 0.9% over 20 minutes. This is followed by whole body imaging to determine whether biodistribution is acceptable, and to allow calculation of the therapeutic dose of radiolabelled tositumomab. In the therapeutic step, tositumomab 450 mg is given again, and followed by the calculated dose of radiolabelled tositumomab. The rate of infusion may be halved for mild to moderate infusional toxicity, and stopped if this is severe; the infusions may be restarted at half the rate once toxicity resolves. Patients are pretreated with thyroid protective agents at least 24 hours before the first radiolabelled dose of tositumomab; treatment is continued until 2 weeks after the radiolabelled therapeutic dose. Analgesics and antihistamines are also given by mouth 30 minutes before doses of tositumomab.
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7. Horning SJ, et al. Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol 2005; 23: 712–19
8. Kaminski MS, et al. I-Tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 2005; 352: 441–9
9. Fisher RI, et al. Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin’s lymphomas. J Clin Oncol 2005; 23: 7565–73
10. Dosik AD, et al. Subsequent therapy can be administered after tositumomab and iodine I-131 tositumomab for non-Hodgkin lymphoma. Cancer 2005; 106: 616–22.

💊 Preparations

Proprietary Preparations

USA: Bexxar.
Published March 22, 2019.