Tositumomab

Information about Tositumomab

Tositumomab is the combination of a monoclonal antibody to CD20 and iodine-131 which is used to treat refractory, advanced non-Hodgkin lymphoma.   

Liver safety of Tositumomab

Tositumomab has not been associated with significant serum enzyme elevations during therapy or to cases of idiosyncratic, clinically apparent liver injury.  However, tositumomab has potent immunosuppressive activity and is probably capable of causing reactivation of hepatitis B in susceptible patients. 

Mechanism of action of Tositumomab

Tositumomab (toe si tue’ moe mab) is a monoclonal antibody to the cell surface antigen CD20 (also known as human B lymphocyte restricted differentiation antigen: Bp35) which is found on mature B cells as well as 90% of neoplastic B cell such as occur in non-Hodgkin lymphoma.  Engagement of tositumomab with CD20 leads to cell lysis and depletion of circulating and tissue B cells for 6 to 8 months.  Tositumomab is given in combination with iodine-131 radiolabelled tositumomab which provides additional antineoplastic activity.  Tositumomab and tositumomab I-131 were approved for use in previously treated, resistant non-Hodgkin lymphoma in the United States in 2003. 

FDA approval information for Tositumomab

Because of declining use and the availability of other anti-CD20 monoclonal antibodies, however, tositumomab was discontinued by its sponsor in 2014. 

Dosage and administration for Tositumomab

Tositumomab was previously available in liquid solution in single use vials of 35 and 225 mg (14 mg/mL) and as Iodine 131 tositumomab solutions of varying concentrations.  Dosing required a 2 part dosimetric step followed 7 to 14 days later by a 2-part therapeutic step.  Tositumomab was meant to be given only for a single course. 

Side effects of Tositumomab

Common side effects included infusion reactions, chills, fever, nausea, fatigue, anemia, thrombocytopenia, neutropenia and infections.  Less common but potentially severe side effects included severe allergic reactions, anaphylaxis, marked bone marrow suppression, thyroid abnormalities and radiation exposure. 

Antineoplastic Agents
Alkylating Agents - Altretamine, Bendamustine, Busulfan, Carmustine, Chlorambucil, Cyclophosphamide, Dacarbazine, Ifosfamide, Lomustine, Mechlorethamine, Melphalan, Procarbazine, Streptozocin, Temozolomide, Thiotepa, Trabectedin
Platinum Coordination Complexes - Carboplatin, Cisplatin, Oxaliplatin
Antibiotics Cytotoxic - Bleomycin, Dactinomycin, Daunorubicin, Doxorubicin, Epirubicin, Idarubicin, Mitomycin, Mitoxantrone, Plicamycin, Mithramycin, Valrubicin
Antimetabolites Antifolates - Methotrexate, Pemetrexed, Pralatrexate, Trimetrexate
Purine Analogues - Azathioprine, Cladribine, Clofarabine, Fludarabine, Mercaptopurine, Nelarabine, Pentostatin, Thioguanine
Pyrimidine Analogues - Azacitidine, Capecitabine, Cytarabine, Decitabine, Floxuridine, Fluorouracil, Gemcitabine, Trifluridine/Tipracil
Biologic Response Modifiers - Aldesleukin (IL-2), Denileukin Diftitox, Interferon gamma
Histone Deacetylase Inhibitors - Belinostat, Panobinostat, Romidepsin, Vorinostat
Hormonal Agents Antiandrogens - Abiraterone, Bicalutamide, Cyproterone, Enzalutamide, Flutamide, Nilutamide
Antiestrogens (including Aromatase Inhibitors) - Anastrozole, Exemestane, Fulvestrant, Letrozole
Selective Estrogen Receptor Modulators - Raloxifene, Tamoxifen, Toremifene
Gonadotropin Releasing Hormone Analogues - Degarelix, Goserelin, Histrelin, Leuprolide, Triptorelin
Peptide Hormones - Lanreotide, Octreotide, Pasireotide
Monoclonal Antibodies - Alemtuzumab, Atezolizumab, Avelumab, Bevacizumab, Blinatumomab, Brentuximab, Cetuximab, Daratumumab, Dinutuximab, Durvalumab, Elotuzumab, Gemtuzumab, Inotuzumab Ozogamicin, Ipilimumab, Necitumumab, Nivolumab, Ofatumumab, Olaratumab, Panitumumab, Pembrolizumab, Pertuzumab, Ramucirumab, Rituximab, Tositumomab, Trastuzumab
Protein Kinase Inhibitors - Abemaciclib, Acalabrutinib, Afatinib, Alectinib, Axitinib, Bortezomib, Bosutinib, Brigatinib, Cabozantinib, Carfilzomib, Ceritinib, Cobimetinib, Copanlisib, Crizotinib, Dabrafenib, Dasatinib, Enasidenib, Erlotinib, Gefitinib, Ibrutinib, Idelalisib, Imatinib, Ivosidenib, Ixazomib, Lapatinib, Lenvatinib, Neratinib, Nilotinib, Niraparib, Olaparib, Osimertinib, Palbociclib, Pazopanib, Ponatinib, Regorafenib, Ribociclib, Rucaparib, Ruxolitinib, Sonidegib, Sorafenib, Sunitinib, Trametinib, Vandetanib, Vemurafenib, Vismodegib
Taxanes - Cabazitaxel, Docetaxel, Paclitaxel
Topoisomerase Inhibitors - Etoposide, Irinotecan, Teniposide, Topotecan
Tyrosine Kinase Receptor Inhibitors See Protein Kinase Inhibitors
Vinca Alkaloids - Vinblastine, Vincristine, Vinorelbine
Miscellaneous - Asparaginase (Pegaspargase), Bexarotene, Eribulin, Everolimus, Hydroxyurea, Ixabepilone, Lenalidomide, Mitotane, Omacetaxine, Pomalidomide, Temsirolimus, Thalidomide, Venetoclax

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