美罗华在淋巴瘤治疗中的应用PPT.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; 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; 1st FDA-approved therapeutic antibody to treat cancer (11/1997) 1st fully integrated into chemo-immunotherapy (R-chemo) 1st and only biologic therapy in combination with chemo (R-CVP, etc) that improved progress-free survival (PFS) in pts with 1st line follicular lymphoma, with emerging trend to improve overall survival for the 1st time 1st treatment of any kind (with CHOP or anthracycline-based chemo) to have improved overall survival (OS) in 1st line DLBCL in more than 25 yrs ; Chimeric mab to CD20, IgG1 Weekly x 4 (375mg/m2): Rapid CD20+B cell depletion in blood (100%-few days), BM (90%-1wk), and LN (80%- a few wks), return normal level in 9-12 months Onset and maximal clinical response: 1mt and 3-4 mts Initial Rx in relapsed FL: 50% ORR (6%CR; 44%PR); mDR 11mt; Re-Rx: ORR 40% (10%CR/30%PR); mDR 15mt Maintenance Rx: Qwk X4 every 6 mt or Q3mt for 2 yrs No change of serum Ig and incidence of infection, and the T cell response from vaccination is still OK ;Anti-idiotype (Id) antibody; ;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, Blo