ASH Annual meeting 2010 Meeting Proceedings

Abstract

The ASH meeting gives the hematology community the opportunity to hear about the latest scientific and educational advances in the field of hematology. During Sunday’s plenary presentation, Dr. Kirit M. Ardeshna challenges the watchful-waiting approach for those patients with asymptomatic advanced-stage follicular lymphoma. Subjects were randomly assigned to one of three arms: Arm A: watchful waiting, Arm B: rituximab 375mg/m2 weekly for 4 weeks, Arm C: rituximab 375 mg/m2 weekly for 4 weeks followed by rituximab maintenance every 2 months for 2 years. At three years, the percentage of patients not having started new treatment was 48 percent in the watchful-waiting arm, 80 percent in the rituximab-induction arm, and 91 percent in the rituximab-maintenance arm. Furthermore, there was a highly significant difference in progression-free survival between all three arms. Currently, there is no difference in overall survival between the three arms with 95 percent of all patients remaining alive. During the same plenary presentation, Dr. Elzbieta Pluskota discussed the role of the integrin co-activator kindlin-2 in angiogenesis and blood vessel integrity. The group utilized a mouse model in which the gene dosage of kindlin-2 was cut in half. They found that prostatic tumors implanted into these mice had shorter and thinner blood vessels and reduced vascular area. The blood vessels that did form were immature and leaky. This blunted angiogenic response led to significantly smaller, more necrotic tumors. The results of these studies identify kindlin-2 as a key mediator of tumor angiogenesis and suggest that targeting of this molecule might be a viable therapeutic strategy. Dr. Neil Shah discussed interim results of “Dasatinib versus imatinib in patients with newly diagnosed CML in the DASISION Trial”. After a minimum of 12 months (mos) of follow-up, dasatinib 100 mg once daily demonstrated significantly higher and faster rates of complete cytogenetic response (CCyR) and major molecular response (MMR) compared to imatinib 400 mg once daily. Continuing on this theme, Dr Timothy P. Hughes reported ENESTnd Update: Continued Superiority of Nilotinib Versus Imatinib In Patients with Newly Diagnosed Chronic Myeloid Leukemia. With longer follow-up, nilotinib was associated with a significantly lower rate of progression to AP/BC on treatment and lower rates of suboptimal response or treatment failure vs imatinib. Nilotinib resulted in fewer CML-related deaths and a higher OS rate vs imatinib. Nilotinib induced superior rates of MMR, CMR, and CCyR vs imatinib in patients with newly diagnosed CML-CP. These results support the potential use of dasatinib and nilotinib as initial treatment for pts with newly diagnosed CML-CP. Finally, Dr. Jorge Cortes presented early results from a randomized trial of oral ponatinib in patients with refractory Chronic Myelogenous Leukemia and other hematologic malignancies. Despite progress in CML therapy, patients who fail 2 or more tyrosine kinase inhibitors, or patients with T315I mutation, have no available treatment options. Ponatinib, an oral multiple TKI, is a potent pan-BCR-ABL inhibitor with activity against all tested imatinib-resistant mutants, including T315I.