Therapeutic monoclonal antibodies, such as the anti-CD20 antibody, provide significant benefits to patients with NHL. In particular, since 2000 various phase III trials have utilized RCTs to compare the treatment effects of conventional chemotherapies vs the addition of rituximab to these therapies. The results indicated that the combination of rituximab and conventional chemotherapy was generally superior both in terms of response rates and survival times. Thus, this combination therapy is gradually becoming the standard. Recently, phase I and II trial results assessing the initial use of a novel anti-CD2 antibody, alone or in combination with rituximab, in patients with recurrent aggressive lymphoma have been published. Determining the usefulness of these new antibodies compared to rituximab requires randomized comparative trials or a demonstration of their effectiveness in rituximab-refractory or relapsed patients after completion of first-line rituximab therapy.
Phase III trials comparing galiximab with rituximab combined with galiximab are in progress. Similar studies will be necessary in the future to assess the effectiveness of many novel anti-CD20 antibodies. Some anticipate that rituximab, in combination with these new anti-CD20 antibodies, will improve response rates and prolong PFS.
Radioimmunotherapy with 90Yttrium-ibritumomab tiuxetan or 131Iodine-rituximab is safe and highly effective in patients with relapsed or refractory (resistant to rituximab-based therapy) FL. The effectiveness of these radiolabeled antibodies needs to be compared to other kinds of therapies in randomized trials.
Idiotype vaccines are immunotherapeutic products which have been developed to induce active and long-lasting immune responses against lymphoma cells. Most of these vaccines use the tumor B cell idiotype (the variable region of the surface immunoglobulin) as a tumor-specific antigen. Several phase I/II clinical trials of idiotype vaccines in FL have been conducted over the last 20 years, of which about 10 have been published and demonstrate the effectiveness of these vaccines. These encouraging results, which seem to indicate that the vaccines prolonged PFS, initiated three phase III RCTs (Biovest, Genitope, and Favrille), however, all of these phase III trials ultimately failed to prolong PFS.
Primary GI-FL is very rare, and this histology represents around 2% of all GI-NHL. Many patients with GI-FL have been found at the early stages, however, the disease lesion is not unifocal, but multifocal, with another lesion in the small intestine, and rituximab with or without chemotherapy for many non-advanced GI-FL cases may also be initiated based on the regimens for nodal FL. However, it has been reported that there was little difference in survival between GI-FL patients with and without therapies. Furthermore, GI-FL itself is very rare, and the management of GI-FL remains controversial at present. Yamamoto et al[24
] recently performed a literature review and reported that only about 25% of primary GI-FL patients underwent observation without therapy, and chemotherapy (or combination with other therapies) was performed in about 50% of all primary GI-FL patients. Ongoing research on biomarkers to guide individualized GI-FL therapy may provide invaluable information which will lead to the establishment of a standard therapeutic regimen.