美罗华在淋巴瘤治疗中的应用演示幻灯片.pptVIP

Lymphoma: A Decade of Rituximab and the Next Chapter;Outline;Monoclonal Antibodies from Hybridoma Technology;History of Monoclonal Antibody (Mab) Therapy;FDA Approved Monoclonal Antibodies;The “Ups Downs” of Monoclonal Antibody (mAb) Development ; 5th most common cancer in both men and women in US Hodgkin’s lymphoma and Non-Hodgkin’s Lymphoma (NHL) Incidence increases 3-4% annually (doubled in last 2 decades), one of only two cancers with continued increase Many sub-types of NHL, majority with B-cell origin -Diffuse large B cell lymphoma (DLBCL): most common NHL (30%) -Follicular lymphoma (FL): 2nd most common NHL (20%) -Mantle cell lymphoma (MCL): poorest prognosis (6-10%) Leading the oncology field in disease biology, diagnosis, and therapy (radiation, chemo, immunotherapy, chemo-immunotherapy) ; Rituximab (Rituxan, MabThera)  Targeted therapy  -CD20 on lymphoma  -direct tumor killing by Rituximab Immunotherapy -host immune system -indirect tumor killing by host immune cells;;Vaccine-like effect after Rituximab Treatment; ;Antibodies: a slow breakthrough of a new technology;;Development of IDEC’s Stock Prices;Phase I: 1993-94 -single dose: 10, 50, 100, 250, 500 mg/m2, No MTD -15 pts: 2 PR (100, 500 mg/m2) -Maloney DG, Blood 84:2457, 1994 Phase I: 1994-95 -multiple dose (weekly x 4): 125, 250, 375 mg/m2, No MTD -20 pts: 6 PRs (1/3 in 125, 2/6 in 250, 3/9 in 375), ORR=33% -Maloney DG, J Clin Onc 15:3266, 1997 Phase II: 1995-96 -Fixed dose (375 mg/m2), weekly x4 (determined by the available Mab) -37 pts: 3 CR/14PR (ORR=46%), mTTP 10.2 months -Maloney DG, Blood 90:2188, 1997 Phase II/III Pivotal trial: 1995-96;Rituximab Pivotal Phase II/IIITrial: Clinical Response in Relapsed Indolent or Follicular Lymphoma;Outline;Randomized Trials of Chemotherapy plus Rituximab versus Chemotherapy Alone in B-Cell Lymphoma;Randomized Trials of Maintenance Treatment with Rituximab versus Observation;Extended Uses of Rituximab: Integration into Lympho