maintitleslide—alwaysusetitlecaseon-researchtopractice.ppt

Efficacy and Safety of Lenalidomide (R) Oral Monotherapy in Patients with Relapsed or Refractory Mantle Cell Lymphoma (MCL): Results From an International Study (NHL-003) Reeder CB et al. ASCO 2009; Abstract 8569. (Poster) Introduction Lenalidomide (R), an immunomodulatory agent, can enhance T-cell and natural-killer-cell activation leading to an improvement in tumor-cell/T-cell synapse formation in B-cell cancers and an enhancement in immune-mediated MCL cell kill R also exerts antiproliferative activity in MCL via enhanced tumor suppressor gene expression (including p21 and SPARC), G1 cell cycle arrest, caspase activation and apoptosis NHL-002: R in relapsed or refractory MCL: ORR = 53%, DoR = 13.7 mos Current study objectives: Interim subset analysis of patients with MCL (n = 54) evaluable for response in NHL-003 (N = 218 patients with aggressive forms of NHL) Evaluate the ORR, DoR, PFS and safety of single-agent R (25 mg/daily d1-21 q28 days) in patients with MCL who had relapsed or were refractory to at least 1 prior treatment regimen Mechanism of Action of Lenalidomide in NHL Summary and Conclusions * * Source: Reeder CB et al. ASCO 2009; Abstract 8569. Source: Reeder CB et al. ASCO 2009; Abstract 8569. In NHL, R enhances tumor suppressor genes (including p21) leading to reduced cyclin-dependent kinase (CDK) activity and reduced phosphorylation of pRb, which results in cellular growth arrest in the G0/G1 phases of the cell cycle. p21 CDK4/6 Cyclin D CDK2 Cyclin E Rb E2F E2F Cell cycle progression G1 arrest P P P Rb Lenalidomide Patient Characteristics and Objective Response 43% 35% 26% PR 14% 18% 17% CR/CRu 57% 14 MCL-stem cell treated 53% 43% ORR 17 MCL-bortezomib treated N MCL, all patients 54 Source: Reeder CB et al. ASCO 2009; Abstract 8569. 3 (1-8) 33.3% 25.9% 32.0% Prior therapies Median no. of prior therapies (range) Refractory to last chemotherapy Prior stem cell transplant Prior bortezomib treatment 53.7% 46.3% International Pro