Drug Combo Improves Survival in Older Adults With AML

Side effects may require hospitalization

• Older adults with AML aren’t typically good candidates for the standard AML regimen of intensive induction chemotherapy
• New research finds that a combination of two drugs — azacitidine plus venetoclax — can extend overall survival in older adults
• Physicians should be prepared to hospitalize older patients who receive this regimen, due to increased risks of cytopenia and infections

The standard treatment for acute myeloid leukemia (AML) is intensive induction chemotherapy, followed by consolidation chemotherapy, a stem cell transplant, or a combination of both treatments. Yet the bulk of this patient population, who are in their late 60s or beyond, either aren’t appropriate candidates for chemotherapy, or don’t respond well to it.

Often these patients receive a hypomethylating drug such as azacitidine, but it has limited benefit for inducing remission and prolonging survival. Now, physicians are looking at the benefit of adding another drug to AML therapy for older adults. “One of the more exciting developments we’ve seen in the treatment of acute myeloid leukemia is the combination of hypomethylating agents, such azacitidine with venetoclax,” according to the University of Miami’s Dr. Mikkael Sekeres, who formally practiced at the Cleveland Clinic.

In a study published in The New England Journal of Medicine, the combination of azacitidine and venetoclax led to a median overall survival of 14.7 months, compared to 9.6 months for azacitidine alone. The question, Dr. Sekeres says, is whether this drug combination should be considered a less-intensive therapeutic approach, or a more intensive approach like 7 + 3.

“I think it falls somewhere in between,” he says, “as patients who get the combination almost invariably wind up hospitalized, have prolonged cytopenias, and are at risk of fungal infections as if they received standard 7 + 3 intensive induction chemotherapy.”

He urges caution when prescribing this drug combination. Anticipate that patients will require hospitalization, and possibly a four-week hospitalization, as if they were getting induction chemotherapy. A number of studies are currently investigating the use of azacitidine and venetoclax as the foundation of triplet therapy in older adults with AML. “I do think that’s the future of treatment approaches,” Dr. Sekeres says.