By Bart Scott, MD
Risk-based therapy of AML has always been challenging to apply to patients with a “normal” karyotype. In the scientific committee session on AML yesterday afternoon, which will be repeated this morning at 9:30 a.m., Drs. David Sternberg, Ruud Delwel, and Clara Bloomfield will discuss the advances made in the management of normal karyotype AML. The focus of these talks will be on specific mutations associated with outcomes and response to therapy in normal karyotype AML. These speakers will highlight a pivotal advancement in the field of hematology. In the future, one can envision that molecular analysis will play an important role in the management of AML, particularly in those patients with an otherwise normal karyotype. In the education session for AML, which took place yesterday morning and will be repeated this morning at 7:30 a.m., Dr. Torsten Haferlach will expand upon the molecular analysis in AML and discuss potential therapeutic targets in AML on the basis of specific acquired molecular defects. Dr. Martin Tallman will discuss curative strategies in acute promyelocytic leukemia (APL), and Dr. Frederick Appelbaum will discuss alternative strategies for stem cell transplantation in AML.
The oral sessions will focus on the biology and pathophysiology of AML, as well as new therapies of AML, excluding transplantation. Major themes in the biology and pathophysiology of AML include epigenetic modification and identification of the progenitor cell in AML. For example, on Monday at 11:00 a.m. (Golden Gate Hall in the San Francisco Marriott), Dr. Jaroslav Jelinek (abstract #312) will discuss the association of hypermethylation of the HOX genes with longer survival in AML, and Dr. Maria Paola Martelli (abstract #307) will present evidence for the cell of origin in AML. In an elegant experiment, the investigators provide evidence that CD34+/CD38- hematopoietic stem cells are the cell of origin for NPM1 mutation positive AML.
There are three separate oral sessions covering non-transplant therapy for AML. Many of the abstracts presented focus on inhibitors of tyrosine kinase, either as sole therapy or in combination with standard therapy. During a Tuesday morning session (7:30 a.m., Room 3020-3022-3024 – West), Dr. Farhad Ravandi and colleagues (abstract # 768) will present data regarding the combination of sorafenib, a multi-kinase inhibitor, with idarubicin and cytarabine to treat newly diagnosed AML. Eighty-eight percent of patients achieved a complete remission with this combination. Dr. Jorge Cortes and colleagues (abstract # 767) will present a phase I study of AC220, a selective second-generation FLT3 tyrosine kinase inhibitor. Dr. Aaron Schimmer and colleagues will present results of a phase I/II trial using an anti-sense oligonucleotide (AEG35156) in combination with idarubicin and cytarabine for relapsed or refractory AML (abstract # 764). The authors will report an overall response of 41 percent.
Another major focus is the incorporation of less toxic therapy in the overall treatment plan for AML in elderly patients. “Advances in Treatment of AML in Older Patients” will take place on Monday at 3:30 p.m. in Room 3020-3022-3024 – West.
Important biologic and therapeutic advancements are underway in AML. The molecular characterization of AML is a major theme at ASH. One can envision a future in which molecular characteristics are used to determine novel therapeutic targets. Several investigators will present the addition of novel therapies to standard induction and consolidation regimens. This remains an exciting time in the field of AML, and hopefully these new areas of investigation will finally lead to a change in the standard of care for AML.
Dr. Scott consults for Celgene.
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