EXPERT ANALYSIS FROM THE NCCN HEMATOLOGIC MALIGNANCIES CONGRESS
SAN FRANCISCO (FRONTLINE MEDICAL NEWS) – After years of stagnation in the field of acute myeloid leukemia – with most standard therapies developed in the 1970s – times are changing, Bruno Medeiros, MD, said at the annual congress on hematologic malignancies held by the National Comprehensive Cancer Network.
“2017 is the year of AML,” he said. Four new therapies have been approved by the FDA since April. They include midostaurin for newly diagnosed, FLT-3–mutated patients; enasidenib, for relapsed/refractory IDH2-mutated patients; CPX-351, for high-risk AML patients; and gemtuzumab ozogamicin for newly diagnosed, CD-33–positive patients.
The new therapies give clinicians hope that a rapidly increasing need can be met. AML incidence has risen from about 9,000 20 years ago to more than 20,000 this year, a jump largely driven by a rise in incidence among older patients. And the relapse rates after front-line therapy range from 35% to 85%, with patients older than 60 years on the higher end of that range.
“Development of novel therapies in order to improve the outcomes of these patients is crucial,” said Dr. Medeiros , director of the inpatient hematology service at Stanford (Calif.) Cancer Institute. “I think all of us in the community hope that this is just the tip of the iceberg – this is just the beginning.”
The field is still struggling to negotiate the newly broadened landscape of AML treatment, he said. For instance, it’s not known exactly which patients are likely to respond to isocitrate dehydrogenase (IDH) inhibitors, he said.
He did offer some guidance on the use of CPX-351, a new formulation of the chemotherapeutic agents cytarabine and daunorubicin that is active in chemotherapy-resistant patients and could be a useful tool leading up to transplant.
“It appears that this drug is able to actually get patients into remission more effectively, leads to fewer toxicities and then allows patients to get to transplant in better shape with better disease response, translating into better overall outcomes,” Dr. Medeiros said.
Many more drugs are in development, with results likely to be revealed soon. Approval for a novel IDH1 inhibitor – only the IDH2 inhibitor is currently approved – is expected early next year. Also under investigation are the hypomethylating agents guadecitabine, a formulation that protects decitabine from degradation, and oral azacitidine, which might be beneficial particularly to patients not eligible for allogeneic stem cell transplant; the B-cell lymphoma 2–inhibitor venetoclax; and an E-selectin antagonist that targets an adhesion molecule in AML cells.
Chimeric antigen receptor T-cell therapy – so promising in other areas of hematologic treatment – is complicated in AML, he said, because of the lack of a target that doesn’t bring on unwanted effects.
“The expression of any antigen in leukemic stem cells is also shared by the expression in hematopoietic stem cells and therefore the use of agents that will target these particular antigens consequently leads to an ‘on-target, off-leukemia’ side effect associated with myeloid cell aplasia.”
Dr. Medeiros reports financial relationships with Celgene, Jazz, Novartis, Pfizer, and other companies.
