ORLANDO -- Six hot topics will take center stage here at the 57th annual meeting of the American Society of Hematology, top officials of the organization said.
Participants can look forward to a "very exciting meeting" with a focus on new research in areas ranging from gene therapy to sickle cell disease, according to society President David Williams, MD, of Boston Children's Hospital.
Gene therapy has had "ups and downs" since the 1980s, but continuing research is promising in several diseases, Williams told reporters in a telephone briefing on the meeting.
One important study, he said, demonstrates that gene therapy can help patients with beta-thalassemia major reduce or eliminate their dependence on transfusions.
In the so-called Northstar study, researchers used a lentiviral vector to transport a functioning hemoglobin gene into patients' own hematopoietic stem cells and then transfused them back into the patients.
Williams cautioned that the study -- a Phase I/II trial -- has just a handful of patients and a short follow-up. But he said about half of the evaluable patients are now living without transfusions and others have reduced their need for the procedure.
He said a similar caution applies to another gene therapy study, this one in older patients with X-linked severe combined immunodeficiency (SCID-X1), the so-called Bubble Boy disease.
The best treatment for infants with SCID-X1 is a stem cell transplant from a matched sibling donor, but for children without such a donor, doctors rely on partly matched stem cells from a parent.
Such a transplant is lifesaving but only partly restores the immune system, so that patients require life-long immunoglobulin treatment, which is both a "quality of life issue and a financial issue," Williams said.
In this study, Williams noted, researchers also used a lentivirus vector to insert a normal IL2RG gene into hematopoietic stem cells in the hope that the cells -- once transfused back -- would improve immune system function.
While only two patients have enough follow-up to be evaluated, he said, they both now have the ability make antibodies and no longer need immunoglobulin.
Shifting gears, Williams highlighted a study that shows an oral medication can be a good alternative to transfusion in patients with sickle cell anemia and a high risk of stroke, as indicated by Transcranial Doppler (TCD) screening.
"We know that if the Transcranial Doppler level is high, then a proportion of patients will go on relatively quickly to a stroke," Williams said.
In such patients, transfusions protect against stroke but have to continue indefinitely, leading to iron overload and serious health problems. So, Williams said, investigators wondered if oral hydroxyurea, used in sickle cell disease to prevent vaso-occlusive painful crises, hospital admissions, and fewer acute chest syndrome, might also help to normalize TCD velocities.
In a 2-year, phase III trial, he said, the oral medication was non-inferior to transfusion, offering an alternative to transfusion, and also showed a trend toward superiority.
Sickle cell disease can be cured with a stem cell transplant, but the approach is more widely used in Europe than in the U.S., Williams said.
"The quandary," he said, "is that you risk acute toxicity, even death, for the cure that you get if the transplant is successful," he said.
A large European analysis of 1,000 patients under 16 who were transplanted after they had a stroke puts some numbers on that risk, he said. Researchers are reporting a mortality rate of 7% and a 3-year overall survival rate of 90% -- figures that are "quite encouraging," Williams said.
Treatment options for relapsed and refractory multiple myeloma have been improved rapidly, commented Stephanie Lee, MD, of the Fred Hutchinson Cancer Center in Seattle, the ASH secretary.
Several studies here are demonstrating continued improvements by adding novel drugs to existing doublet therapy, Lee told reporters.
For instance, she said, interim results from the phase III Tourmaline-MM1 study show positive outcomes after adding ixazomib, an oral proteasome inhibitor, to standard care with lenalidomide (Revlimid) and dexamethasone.
And a phase I/II study of daratumumab, a human anti-CD38 IgG1κ monoclonal antibody recently approved under the name Darzalex, is finding good response rates when the drug is combined with lenalidomide and dexamethasone, Lee said.
The studies "make me wonder if quadruple therapy is going to be next," she said.
Aside from those areas, Williams said, participants can also expect important new information about immunomodulatory therapy, precision medicine, and recently approved medications, including a special session that will focus on drugs approved in the month before the meeting.