Radioimmunotherapy of lymphomas

Lymphomas, especially non-Hodgkin's lymphomas (NHL), are increasing in frequency. In the US, last year over 50,000 cases were diagnosed. Most NHL are 'B' cell in origin, and thus express many normal 'B lymphocyte' surface markers. A variety of monoclonal antibodies reactive with normal B-cells, and thus with B-cell lymphoma, have been produced. In addition, monoclonal antibodies reactive with the surface immunoglobulin, expressed by many B-cell lymphomas, the 'anti-iodotypic' have been made. The pan B-cell antibodies are not tumor specific, but are B-cell specific, while the anti-iodotypic antibodies are truly 'tumor specific'. Several of these antibodies have been radiolabeled with I-131 or Y-90 and have been used in clinical trial. To varying degrees, all have shown at least some anti tumor activity. Antibodies to the CD-37 marker and to CD-20 have been most explored at the University of Michigan. The anti CD-37 results showed occasional remission, but poor durability. By contrast, the results with I-131 and anti B-1 (anti CD-20) have shown frequent remission (± 75%) with a high frequency complete remission with good durability (median > 15 months). The approach in Ann Arbor has been to use 'non-myelo-ablative' treatment. Other groups using Lym-1 (DeNardo et al) and LL-2 (Goldenberg et al) have also shown anti tumor activity in man with the pan B-cell antibodies. Approaches using myelo-ablative doses of RIT have also been used, with high response rates observed (University of Washington). Results with anti-iodotypic antibodies have been more modest, and this approach is not yet being commercialized. By contrast, there are four commercially sponsored radiolabeled anti lymphoma treatment trials ongoing in the US. It is thus quite likely that one or more anti pan B-cell antibodies will become available for clinical use in the coming years. The I-131 anti B-1 reagent is in phase III trials and has been used in the largest number of patients. This lecture will update the audience on lymphoma RIT and will highlight the clinical results with I-131 anti B-1