The Changing Treatment Landscape for Multiple Myeloma

Four new drugs for the treatment of multiple myeloma recently entered the marketplace, changing the standard care for cancer patients with this disease, a new study suggests.

In February 2015, the FDA approved the first histone deacetylase inhibitor panobinostat (Farydak). The approval came from the PANORAMA-1 study that showed a 4-month increase in median progression-free survival when Farydak was added to bortezomib (Velcade) and dexamethasone.

In November 2015, the FDA granted accelerated approval to the first immunotherapy for multiple myeloma daratumumab (Darzalex). The second immunotherapy option, elotuzumab (Empliciti), received approval in December.

Lastly, the fourth multiple myeloma drug to be approved was an oral proteasome inhibitor called ixazomib (Ninlaro).

“This is an extraordinary moment in oncology,” said Paul G. Richardson, MD, Director of Clinical Research at Jerome Lipper Multiple Myeloma Center in the study, published in American Health & Drug Benefits. “(The monoclonal antibodies) may override the impact of mutations and provide entirely non—cross-resistant strategies, so we can add them to existing drugs.”

Although the 4 newly approved drugs were indicated for use in advanced multiple myeloma, the FDA approved a new indication for lenalidomide (Revlimid) in combination with dexamethasone for patients who are newly diagnosed.

“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,” Kenneth C. Anderson, MD, Program Director of Jerome Lipper Multiple Myeloma Center said in the study. “We now have clinical evidence demonstrating that starting and keeping newly diagnosed multiple myeloma patients on lenalidomide significantly improve progression-free survival.”

Relapse and refractory disease remains a challenge for researchers. Once multiple myeloma becomes refractory to a proteasome inhibitor and to an immunomodulatory drug (IMiD), median event free survival is around 5 months and the overall survival is only 9 months, the study noted.

“In myeloma, you can revisit classes of drugs that you previously gave, recognizing that rational combinations of the same drugs make sense as you seek to salvage your patient,” Richardson said. “Tolerability and quality of life should be kept in mind in ensuring patients not only to live longer, but to live well.”

In July 2015, carfilzomib (Kyprolis) gained new indication in combination with Revlimid and dexamethasone for patients who received 1 to 3 prior therapies and had relapsed.

Additionally, a study showed that triplet therapy was superior to doublet therapy. Combinational drugs Revlimid, Velcade, and dexamethasone prolonged survival over Revlimid and dexamethasone.

Off-label use of the 4 new agents will also be appealing for newly diagnosed myeloma patients. Elderly patients with standard-risk myeloma could substitute Ninlaro for Velcade, plus Revlimid and dexamethasone.

“This is a very simple regimen, as you take just 3 drugs a month, and the side-effect profile is outstanding,” said Vincent S. Rajkumar, MD, in the study.

Patients with a high risk for cytogenetics could consider adding Darzalex or Empliciti to a triplet regimen for a more aggressive treatment from the beginning. However, monoclonal antibodies should not immediately be added to frontline treatment because of costs and side effects, according to the study.

For relapsed or refractory patients, Ninlaro shows promise because of strong tolerability and weekly dosing. In patients with high risk myeloma who need a proteasome inhibitor, a combination of Revlimid and dexamethasone would be the most useful for treatment.

Researchers stress that myeloma patients are likely to use all of the new drugs at one time or another, but new small molecule inhibitors and checkpoint inhibitors in the pipeline will most likely be needed.