[Recent progress in rituximab therapy and its resistance--how do we overcome?].
With the introduction of rituximab to chemotherapy in lymphoma, CHOP changed to R-CHOP in elderly, intermediate risk DLBCL (diffuse large B-cell lymphoma) patients. Although the treatment is not yet standard, due to insufficient evidence, in clinical practice it is an R-containing regimen, for example, in mantle cell lymphoma, such as HyperCVAD/MA to R-HyperCVAD/MA. Recently, another group and ours reported the presence of rituximab resistance during R-containing chemotherapy. If the lymphoma is bulky,the overexpression of CD 55 (complement regulatory molecule) leads to resistance to rituximab. When the patients evidenced the loss of CD 20 antigen in refractory/relapsed lymphoma after R-containing therapy, some patients showed the presence of CD 20 point mutation. In the cases of refractory/relapsed cases, radioimmunotherapy or other monoclonal antibodies are prepared, including Zevalin and CD 22, CD 40, CD 74, and HLA-DR targeting antibodies. Not only monoclonal antibodies but also HDACI or bortezomib (NF-kappaB) and other signal inhibitors (for Akt, ERK/MAPK) have been developed. In Japan, we must consider the higher speed of infusion rituximab and we must prepare standard therapy for lymphoma because of recruiting phase I/II clinical trials after use of rituximab for easy entry.
Dept. of Medical Oncology, and Hematology, Cancer Institute Hospital, Japan.
Kiyohiko
K
Hatake
Masahiro
M
Yokoyama
Yasuhito
Y
Terui
D000368:Aged; D000911:Antibodies, Monoclonal / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20 / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001897:Boronic Acids / Q000627:therapeutic use; D000069286:Bortezomib; D018958:CD55 Antigens / Q000096:biosynthesis; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm; D056572:Histone Deacetylase Inhibitors; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology*; D017354:Point Mutation; D011241:Prednisone / Q000008:administration & dosage; D011719:Pyrazines / Q000627:therapeutic use; D000069283:Rituximab; D014750:Vincristine / Q000008:administration & dosage
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D000970:Antineoplastic Agents; D001897:Boronic Acids; D018958:CD55 Antigens; D056572:Histone Deacetylase Inhibitors; D011719:Pyrazines; D000069283:Rituximab; D014750:Vincristine; D000069286:Bortezomib; D004317:Doxorubicin; D003520:Cyclophosphamide; D011241:Prednisone