Rituximab Maintenance Stage IIIIV Follicular Lymphoma ECOGCALGB E

Rituximab Maintenance: Stage III/IV Follicular Lymphoma (ECOG/CALGB E 1496) Subset: 237 FL pts CVP x 6 -8 → PR/CR (cyclophosphamide, vincristine, prednisone) R A N D O M I Z E Observation (OBS) vs Rituximab Maintenance (MR) OBS MR CVP ORR 83% 86% PFS (4 yr) 33% 56% 13 61 75% 91% PFS median (mo) OS (42 mo) P =. 03 (one-sided) Hochster H et al. ASH 2005. Abstract 349.

CVP + Rituximab: Stage III/IV Follicular Lymphoma Stage III/IV FL → R A N D O M I Z E CVP x 4 vs R-CVP x 4 R E S T A G E CVP x 4 CR/PR → vs R-CVP x 4 CVP = cyclophosphamide, vincristine, prednisone CVP N=159 R-CVP N=162 CR 7. 5% 30% ORR 56% 81% PFS median (mo) 20. 5 44. 8 OS (42 mo) 81% 89% P value . 0553 Solal-Celigny P et al. ASH 2005. Abstract 350.

Maintenance Rituximab: Relapsed Stage III/IV Follicular Lymphoma • Intergroup Phase 3 (update) CHOP vs R-CHOP → Observation vs Maintenance Rituximab – Randomization 1: R-CHOP vs CHOP • CR: 29% vs 16% (P <. 0001) • PFS, median: 33 months vs 20 months – Randomization 2: Maintenance Rituximab vs Observation • PFS: 52 months vs 15 months, P <. 0001 • OS, 3 years: 85 months vs 77 months, P =. 01 Benefit with maintenance rituximab even after R-CHOP • GLGLSG Phase 3: Relapsed/refractory FL; Mantle cell FCM vs R-FCM → Observation vs Maintenance Rituximab – Overall benefit of MR: median response duration for MR not reached ( vs 17 months in the observation arm) – Role of MR following R-FCM in FL: median response duration for MR not reached (vs 26 months in the observation arm) Van Oers et al. ASH 2005. Abstract 353. Hiddemann et al. ASH 2005. Abstract 920.

R-CHOP-14 vs CHOP-14: DLBCL* RICOVER-60: Interim analysis (n=828) Results 6 CYCLES vs 8 CYCLES -No differences for entire population -Small nonsignificant benefit for CHOP-14, 8 vs 6 -No benefit for R-CHOP-14, 8 vs 6 R-CHOP-14 vs CHOP-14 -CR, 81% vs 73% (P =. 008) -Time to treatment failure (at 26 months), 70% vs 57% (P =. 000025) HOVON/Nordic Lymphoma Group: Interim analysis (n=250)–DLBCL, FL, MCL Results CHOP-14 x 8 v R-CHOP-14 x 8 -CR, No difference Failure-free survival (at 18 months) favors R-CHOP-14: 51% vs 33%, P =. 005 Conclusion: Dose-dense R-CHOP is feasible and produces results superior to dose-dense CHOP. Results need to be confirmed. Pfreundschuh M et al. ASH 2005. Abstract 13. Sonneveld, P et al. ASH 2005. Abstract 16. *61 -80 years of age

Immunomodulatory Drugs in CLL Phase 1/2 Initial Therapy With Fludarabine and Thalidomide in Stage I-IV CLL N=13 (evaluable) -10 CR (77%), 3 PR (23%) -Overall response rate, intent-to-treat population 100% • Flare reaction, 46% • Nonhematologic grade 3/4 toxicities, 11% (diarrhea, fatigue, pedal edema) Phase 2 Study of Lenalidomide in Relapsed/Refractory CLL N=17 (evaluable) -2 CR (11. 7%), 9 PR (52. 9%), 5 SD (24. 9%), 1 PD • Flare reaction, most patients • Grade 3/4 hematologic toxicity (7), tumor lysis syndrome (2), febrile neutropenia (3) Chanan-Khan AA. ASH 2005. Abstracts 2974 and 447.