In December 2015, thousands of experts gathered in Florida for the Annual Meeting of the American Society of Hematology. Several special sessions at the meeting were focused on these new developments, highlighting the implications for patients with multiple myeloma.
“This is a revolutionary time in multiple myeloma,” said S. Vincent Rajkumar, MD, Professor of Medicine at the Mayo Clinic in Rochester, MN, at the meeting. “Darzalex, Empliciti, and Ninlaro promise to change the landscape of treatment and improve overall survival,” he said.
“This is an extraordinary moment in oncology,” agreed Paul G. Richardson, MD, Director of Clinical Research of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
FDA Approves 4 New Drugs in 2015
In February 2015, the FDA approved Farydak (panobinostat), the first new drug known as an HDAC inhibitor for multiple myeloma. The FDA accelerated the approval based on results from clinical trials showing that adding Farydak to Velcade (bortezomib) and Decadron (dexamethasone) slows the disease progression.
In November, the FDA approved Darzalex (daratumumab), the first monoclonal antibody (immunotherapy) for multiple myeloma.
In December, the FDA approved the second monoclonal antibody, Empliciti (elotuzumab), for patients with this disease.
Darzalex and Empliciti harness the patient’s immune system to attack the cancerous blood cells of patients with multiple myeloma.
Later in December, Ninlaro (ixazomib) was the fourth drug to receive FDA approval in 2015 and the first oral proteasome inhibitor, making it a convenient new option for patients and charting a new direction for this type of drugs.
Dr. Richardson called the new monoclonal antibodies “paradigm-changing” medications in multiple myeloma, especially in the treatment of patients with high-risk disease. These drugs, he said, “may override the impact of mutations” and provide new strategies, “so we can add them to existing drugs.”
A New First-Line Treatment Option
In addition, patients who are newly diagnosed with multiple myeloma now have a novel treatment option, with the 2015 FDA approval of a new indication for Revlimid (lenalidomide), which was previously available only for patients with advanced disease.
“The approval of lenalidomide as an option for use in all patients with multiple myeloma represents a new paradigm in the management of this disease,” said Kenneth C. Anderson, MD, Program Director, Jer-ome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston. “We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on lenalidomide significantly improve progression-free survival.”
Dr. Rajkumar said that this new indication for Revlimid (which is used with Decadron) firmly establishes this combination as the backbone for future treatment regimens. Currently clinical trials are investigating the use of Revlimid plus Decadron in combination with Ninlaro, Empliciti, or Darzalex for first-line treatment of all patients.
These 3 new drugs, said Dr. Richardson, “add profoundly to the armamentarium” for treating patients with advanced disease. “The important message is that in the last 3 months, we have 3 very important agents here.”
3-Drug Therapy a New Standard
Several experts suggested that the use of a 3-drug regimen should now be the new treatment standard. One study with Revlimid, Velcade, and Decadron demonstrated extended survival with the 3 drugs over Revlimid plus Decadron alone.
The treatment of multiple myeloma is clearly changing toward the use of 3 drugs. The recent availability of the new oral therapy with Ninlaro now makes it possible to use 3 oral drugs together, adding an element of patient convenience that will be very attractive for patients.
Furthermore, although the 4 new drugs are approved for use after patients have tried other therapies, Dr. Rajkumar said that doctors will certainly be tempted to use the new drugs even earlier.
For example, for frail or elderly patients, it would make sense to replace Velcade with Ninlaro in combination with Revlimid and Decadron.
“This is a very simple regimen, as you take just 3 drugs a month, and the side-effect profile is outstanding,” Dr. Rajkumar said, adding that Ninlaro will also be useful for patients who cannot take Velcade (a proteasome inhibitor available only for intravenous and subcutaneous administration).
