Slide Show: 2013 American Society of Hematology Meeting and Exposition

Slide 1: Novel Anti-CD20 Antibody, Obinutuzumab, Bests Rituximab in Head-to-Head Trial of Newly Diagnosed Chronic Lymphocytic Leukemia PatientsThe large, randomized phase III CLL11 trial showed a better progression-free survival for patients treated with the anti-CD20 antibody obinutuzumab (GA101) plus chlorambucil compared with the anti-CD20 antibody rituximab plus chlorambucil (median progression-free survival of 26.7 months vs 15.2 months, respectively). The results suggest obinutuzumab plus chlorambucil could replace this current standard of care for newly treated chronic lymphocytic leukemia patients who have comorbidities.Source: Goede V, Fischer K, Busch R, et al. Head-To-Head Comparison Of Obinutuzumab (GA101) Plus Chlorambucil (Clb) Versus Rituximab Plus Clb In Patients With Chronic Lymphocytic Leukemia (CLL) and Co-Existing Medical Conditions (Comorbidities): Final Stage 2 Results Of The CLL11 Trial. ASH 2013; Abstract 6.Slide 2: Researchers Identify Unique (and Previously Elusive) Mechanism of LenalidomideLenalidomide is a widely used immunomodulating agent for the treatment of multiple myeloma, mantle-cell lymphoma, and certain myelodysplastic syndromes. But how lenalidomide works on a cellular level has been far from clear. In a study presented at the late-breaking session at the 55th American Society of Hematology Meeting and Exposition, Jan Krönke, MD, of the Brigham and Women’s Hospital in Boston, found that the drug selectively promotes degradation of two transcription factors (IKZF1 and IKZF3) essential for multiple myeloma cells by binding them to a ubiquitin.Source: Krönke J, Udeshi N, Narla A, et al. Lenalidomide Promotes CRBN-Mediated Ubiquitination and Degradation of IKZF1 and IKZF3. ASH 2013; Abstract LBA-5.Slide 3: Continuous Lenalidomide Plus Low-Dose Dexamethasone Improves Progression-Free Survival in Patients With Newly Diagnosed Multiple MyelomaContinuous treatment with lenalidomide plus low-dose dexamethasone improved progression-free survival in newly diagnosed multiple myeloma patients who are not eligible for a stem cell transplant. The FIRST trial, a phase III study that involved 1,623 patients, showed that the combination given continuously was better than either standard of care or lenalidomide plus low-dose dexamethasone given for a defined amount of time (72 weeks). Progression-free survival was 25.5 months in the continuous treatment arm compared with 21.2 months in the standard of care arm (P = .00006) and 20.7 months in the 72-week combination arm.Source: Facon T, Dimopoulos MA, Dispenzieri A, et al. Initial Phase 3 Results Of The First (Frontline Investigation Of Lenalidomide + Dexamethasone Versus Standard Thalidomide) Trial (MM-020/IFM 07 01) In Newly Diagnosed Multiple Myeloma (NDMM) Patients (Pts) Ineligible For Stem Cell Transplantation (SCT). ASH 2013; Abstract 2.Slide 4: Oral PI3 Kinase Inhibitor IPI-145 Has Promising Activity in Relapsed, Refractory Chronic Lymphocytic LeukemiaA 193-patient phase I trial shows that the oral agent IPI-145, an inhibitor of the delta and gamma isoforms of PI3 kinase, is active in both relapsed, refractory, and treatment-naive patients, including patients carrying a 17p deletion. The overall response rate in 43 relapsed, refractory chronic lymphocytic leukemia patients was 47%. Of six high-risk treatment-naive patients, three had a nodal response.Source: Flinn I, Patel M, Kahl BS, et al. Preliminary Safety and Efficacy Of IPI-145, a Potent Inhibitor Of Phosphoinositide-3-Kinase-δ,γ, In Patients With Chronic Lymphocytic Leukemia. ASH 2013; Abstract 677.Slide 5: Combination Oral PI3K Inhibitor Plus Anti-CD20 Antibody Shows Promise in Previously Treated Chronic Lymphocytic Leukemia PatientsThe combination of idelalisib, an oral PI3 kinase delta inhibitor, plus rituximab, an anti-CD20 antibody, improved both progression-free and overall survival in previously treated chronic lymphocytic leukemia patients when compared with rituximab alone. Progression-free survival at 24 weeks was 93% in the combination arm compared with 46% in the rituximab plus placebo arm. The 220 patients enrolled to the phase III trial continue to be followed up to assess the durability of responses.Source: Furman RR, Sharman JP, Coutre SE, et al. A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Idelalisib and Rituximab for Previously Treated Patients with Chronic Lymphocytic Leukemia (CLL). ASH 2013; LBA-6.