FROM A TELECONFERENCE – The American Society of Hematology’s (ASH) 57th annual meeting in Orlando is chock-full of much-anticipated results in cancer immunotherapies such as CAR T cell therapies and checkpoint inhibitors, advances in sickle cell disease, and practical advice on managing the latest drugs in the clinic, ASH officials said in a teleconference. Here are some of the day-by-day picks selected by ASH president Dr. David Williams and ASH secretary Dr. Stephanie J. Lee, who gave their recommendations during a conference call for the press. Meeting abstracts are now available online.
Saturday, Dec. 5
Clinical applications of newly approved drugs
The popular special education session on clinical applications of newly approved drugs returns on Saturday, Dec. 5 at 9:30 a.m., with didactic presentations that address issues clinicians may face such as drug-drug interactions, side effects, and adverse events. The three drugs to be discussed this year are: idarucizumab (Praxbind), the first specific reversal agent approved for dabigatran reversal; blinatumomab (Blincyto), approved for second-line treatment of Philadelphia chromosomenegative acute lymphoblastic leukemia; and the histone deacetylase (HDAC) inhibitor panobinostat (Farydak), approved for the treatment of multiple myeloma.
Adoptive immunotherapy
One presentation to look out for next month is abstract 99at 12:30 p.m. on Saturday, Dec. 5 in the adoptive immunotherapy session, Dr. Williams told reporters. The chimeric antigen receptor (CAR)-T-cell approach has relied on genetically engineering the patient’s own T cells to rev up the immune system. This group’s approach is to treat B-cell malignancies after allogeneic hematopoietic stem cell transplantation using a single infusion of anti-CD19 CAR-T cells from the patient’s transplant donor.
Eight of 20 patients treated with this strategy achieved remission, including six complete remissions and two partial remissions. Importantly, none of these patients developed acute graft-versus-host disease, a potential consequence of using allogeneic rather than autologous T cells, he said. The authors also noted that patients who responded and went into remission were marked by higher numbers of these infused CAR-T cells in their circulation, suggesting a biomarker of response.
Checkpoint, please?
Immunotherapy is a “very hot area,” so ASH has put together a special session at 4 p.m. Saturday called “Checkpoint, Please?” Dr. Williams said. Topics include the role of programmed death (PD)-1 and PD-ligand 1 in acute and chronic graft-versus-host disease, checkpoint blockade with neoantigen cancer vaccines, and insights into the mechanisms of action of anti-CTLA-4 (cytotoxic T-lymphocyte–associated protein 4) antibody therapy.
Sunday, Dec. 6
Precision medicine
Sunday’s plenary scientific session will include several noteworthy personalized medicine abstracts featuring emerging therapies targeted to specific genetic subtypes, Dr. Lee, from the University of Washington, Seattle, said.
Plenary abstract 6 is a large, multinational study looking at whether adding the multikinase inhibitor midostaurin to standard induction therapy and carried through 1 year of maintenance would improve outcomes in newly diagnosed acute myeloid leukemia with FLT3 mutations. Patients with these deleterious mutations do enter remission with chemotherapy, but often relapse.
Overall and event-free survival were better at 5 years by about 7% to 8% in the experimental arm using midostaurin, she said. Caveats are that complete response rates were similar in both arms and lower than reported in other trials.
“Because we know that patients with this FLT3 mutation have a very poor prognosis with standard chemotherapy, more than half of the patients in this trial received an allogeneic transplant,” Dr. Lee noted. “But the abstract does say that the results are similar if you censor at the time of the transplant.”
In this same vein of precision medicine is plenary abstract 1, testing whether adding rituximab to standard chemotherapy improves outcomes in adults with CD-20–positive, Philadelphia chromosome–negative, B-cell precursor acute lymphoblastic leukemia (ALL). Rituximab (Rituxan) binds to CD-20, which is found in about 30% to 50% of adult B-cell ALL, she said.
At 2 years, patients treated with rituximab had longer event-free survival than controls (65% vs. 52%; P = .038), but similar overall survival (71% vs. 64%; P = .09), according to the abstract. The rituximab arm also received more allogeneic transplants, but again, after censoring the data, the abstract states that both event-free and overall survival were longer with rituximab, Dr. Lee said.
Sickle cell anemia
Sunday’s plenary session will also feature the very important TWiTCH (TCD with Transfusions Changing to Hydroxyurea) study evaluating hydroxyurea therapy as an alternative to chronic blood transfusions to prevent stroke. Stroke is one of the most dreaded complications of sickle cell disease, occurring in up to 10% of children, Dr. Williams said. Though transfusions are effective, they have to be continued indefinitely and lead to iron overload. Hydroxyurea increases the amount of fetal hemoglobin and fetal red blood cells and has become a standard therapy to attenuate the complications of sickle cell.