Pomalidomide (Pomalyst) rode impressive trial results to accelerated FDA approval last year, and Kenneth Anderson thinks it will prove a valuable new tool in the fight against multiple myeloma.
Better still, Anderson sees equally promising compounds at various stages of development and equally promising treatment trends that range from the transition to oral treatment regimes to the evaluation of early intervention efforts.
“The last two big drugs to be approved, pomalidomide and carfilzomib [Kyprolis], are second-generation compounds that work along similar principles as earlier medications in these classes, but to much greater effect,” Anderson said. “Looking down the road, however, the most promising names mostly belong to new monoclonal antibodies that haven’t been used against multiple myeloma before.”
Among the most exciting of the experimental compounds is elotuzumab, a monoclonal antibody currently in phase III trials for advanced disease in previously treated patients. In earlier trials, elotuzumab combined with lenalidomide (Revlimid) and dexamethasone (Decadron) has produced responses in up to 92% of such patients. Progression-free survival times have approached 3 years.
“Those numbers are really quite remarkable,” said Anderson, who hopes the drug replicates those figures in the last trial phase and wins approval in the next year or two.
Looking further down the development pipeline, Anderson noted that the FDA has awarded breakthrough status to daratumumab based on phase I trial results. The IgG1k monoclonal antibody, which targets the CD38 surface protein on myeloma cells, produced significant benefit in 47% of patients, most of them with advanced double-refractory disease. Progression-free survival exceeded 8 months for some patients, even though treatment stopped after eight cycles.
Moving from individual medications to trends, Anderson sees great potential in trials that combine classes of medications in new and potentially more effective ways. For example, researchers are pairing HDAC inhibitors with proteasome inhibitors, and also with immunomodulatory drugs. The potential exists, down the road, for a four or five-tier treatment that adds a monoclonal antibody to the mix in such a way that the benefit of each drug is additive or synergistic—hopefully enough to achieve cure.
So many medications could not have been used together a couple of decades ago, Anderson noted, because the side effects of each existing treatment was severe. Today’s medications, however, are not only more effective but also well tolerated, so we can contemplate using them in novel ways.
Another potentially transformative example of this, according to Anderson, is using the treatments to nip the disease in the bud by treating smoldering myeloma rather than waiting to see which cases progress.
“We don’t know that we can prevent development of active multiple myeloma,” Anderson said, “but our tools for both diagnosis and treatment have improved to the point that early treatment to prevent active disease can now be studied.”
Kenneth C. Anderson, MD, is program director and chief of the Division of Hematologic Neoplasias at the Dana-Farber Cancer Institute, and Kraft Family Professor of Medicine at Harvard Medical School in Boston, Massachusetts. –