WHAT's HOT AT ASH

Progress in the treatment of many blood disorders as well as blood cancers will be reported at the American Society of Hematology (ASH) 57th Annual Meeting, which is being held this weekend in Orlando, Florida.

For hematologic malignancies, two large trials will be presented at the plenary session on Sunday, December 6. Both are likely to change clinical practice, says David Steensma, MD, senior physician at the Adult Leukemia Program in the Hematological Malignancies Division at the Dana Farber Cancer Institute, in Boston, Massachusetts. Dr Steensma is education co-chair for the meeting, and he was speaking to journalists in a premeeting presscast.

One of the trials to be featured at the plenary session is the Graall-R2005 study, which explores a potential new use for rituximab (Rituxan, Biogen/Genentech) in the treatment of acute lymphoblastic leukemia (ALL).

Rituximab is already a mainstay in the treatment of lymphoma, but this new trial provides data showing a benefit in ALL for patients aged 18 to 59 years. "This is a very curable malignancy in children, but it has poor outcomes in adults," Dr Steensma commented. These new results will "immediately change clinical practice," he predicted, especially because the drug is already on the market.

The other trial is also likely to change practice, but only in the future, because the drug is an investigational agent and is not yet available. Midostaurin, which is under development by Novartis, is a multikinase inhibitor that has been shown to improve overall survival when added to chemotherapy in the treatment of newly diagnosed acute myeloid leukemia. This is the first time in 30 years that an addition to the standard chemotherapy regimen has been shown to make a difference in outcomes, Dr Steesma commented. These data come from the CALGB 10603/RATIFY study, sponsored by the Alliance for Clinical Trials in Oncology.

Gene Therapy for Blood Disorders

For blood disorders, there is excitement that at last, all the research efforts into gene therapy are now yielding results that show both safety and clinical benefit, Dr Steensma commented.

New studies to be presented at the meeting include one experimental gene therapy for older patients with X-linked severe combined immunodeficiency and another for patients with rare Wiskott-Aldrich syndrome, which is characterized by thrombocytopenia, recurrent infections, easy bruising, bleeding, eczema, autoimmune disorders, and high susceptibility to cancer.

In addition, new results will be presented for gene therapy for patients with beta-thalassemia major, as well as for patients with severe sickle cell anemia and beta-thalassemia major.

"It's early days yet, and these are small numbers of patients," Dr Steensma cautioned, but it now appears that "gene therapy is making its way into clinical practice for these severe inborn disorders."

Big Splash Again With CAR T-Cells

Further progress with chimeric antigen receptor (CAR) T-cells in the treatment of various blood cancers will be reported. This investigational approach has made a huge splash at the ASH meeting in previous years, showing unprecedented responses in a number of leukemias and lymphomas, as previously reported by Medscape Medical News.

CAR T-cells will "make a big splash again" this year, predicts Miguel-Angel Perales, MD, deputy chief at the Adult Bone Marrow Transplant Service at the Memorial Sloan Kettering Cancer Center, New York City. He highlights what he sees as the most interesting abstracts in a companion article. For the first time, activity of CAR T-cells in the treatment of multiple myeloma will be reported.

Guidance on Using New Drugs

The past few years have seen an avalanche of new drugs being approved for use in hematologic malignancies, with four products launched for chronic lymphocytic leukemia in 2014, and three new drugs approved for multiple myeloma in just the past 3 weeks.

The new arrivals widen the choice of available therapies, but they can also present clinicians with a bit of a headache in trying to keep up with which drug to use when and in what patient population. The ASH meeting has a special session geared to just this, focusing on clinical applications of newly approved drugs. The presenters "will have significant clinical experience with the new agents," and the "focus of the session will be on issues clinicians face in treating patients with the new drugs: appropriate population, dosing, side effects, adverse events, drug-drug interactions, and off-label use," the program promises.

The following new drugs will be discussed at a session on Saturday, December 5, from 9:30 to 11:00 am:

• Idarucizumab (Praxbind, Boehringer Ingelheim Pharmaceuticals, Inc), which rapidly reverses the effects of the anticoagulant dabigatran (Pradaxa, Boehringer Ingelheim Pharmaceuticals, Inc). As the first antidote to non–vitamin K antagonist oral anticoagulants, it has been hailed as a "game-changer" and a "breakthrough." This product was approved by the FDA in October 2015. At the ASH meeting, it will be discussed by Kenneth A. Bauer, MD, Beth Israel Deaconess Medical Center, Boston, Massachusetts.
• Blinatumomab (Blincyto, Amgen Inc), a new agent for use in the treatment of patients with Philadelphia chromosome–negative precursor B-cell ALL. It has a unique mechanism of action and is the first of a novel class of drugs known as bispecific T-cell engagers, which are designed to direct cytotoxic T-cells to cancer cells that express CD19 (which is expressed on the surface of B-cell-derived ALLs and non-Hodgkin's lymphomas). The product was approved in December 2014 and will be discussed at the meeting by Anjali S. Advani, MD, Cleveland Clinic, Cleveland, Ohio.
• Panobinostat (Farydak, Novartis Pharmaceuticals Corporation), the first in a new class of agents that act as inhibitors of histone deacetylases. Panobinostat was approved by the FDA for use in the treatment of multiple myeloma in February 2015. It will be discussed at the meeting by Sagar Lonial, MD, from the Winship Cancer Institute, Emory University School of Medicine, Atlanta, Georgia.