In a trio of studies to be presented at the 57th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, investigators at Dana-Farber Cancer Institute will present the results of clinical trials showing that new drug combinations can significantly extend the time in which multiple myeloma is kept in check in patients with relapsed or treatment-resistant forms of the disease.
The trials pair the oral drugs lenalidomide and dexamethasone with other agents, each of which exploits a different vulnerability in tumor cells. The various combinations are at different stages of clinical testing, but all are proving effective at producing at least partial remissions and increasing the duration of those remissions, with tolerable side effects for most patients.
"With the recent approvals of daratumumab, ixazomib, and now elotuzumab, we have seen an unprecedented pace of progress in myeloma therapy this year. The results from these studies reflect the real benefits our patients can anticipate from these very important advances in currently available treatment," said Paul Richardson, clinical program leader and director of clinical research at Dana-Farber's Jerome Lipper Multiple Myeloma Center.
All of the patients in the three trials had myeloma that had either relapsed or become resistant to other therapies. Patients received a tandem of lenalidomide, a drug that kills tumor cells, blocks blood vessel growth, and acts on the immune system, and dexamethasone, an anti-inflammatory agent, plus one of three new agents:
- A combined phase 1 and phase 2 trial of lenalidomide/dexamethasone plus a breakthrough antibody therapy called daratumumab (Darzalex™). Of 32 patients participating in the trial, 11 had a partial response to the drug regimen, meaning a decrease in the extent of the cancer, and 53 had a very good partial response, meaning the level of certain myeloma-related proteins in the blood declines by more than 90 percent. In 93 percent of cases, remissions lasted for the entire 12 months that the patients have been tracked so far. The most common adverse side effects were neutropenia (a shortage of certain white blood cells), muscle spasms, cough, diarrhea, fatigue, and hypertension.
Abstract # 507:
- A phase 3 trial of lenalidomide/dexamethasone plus ixazomib (Ninlaro®), a 'proteasome inhibitor' that blocks the ability of cancer cells to reuse certain proteins. The U.S. Food and Drug Administration approved the drug on Nov. 20 for patients with myeloma who have received at least one previous therapy. In the trial, patients receiving all three drugs had a 35 percent improvement in progression-free survival -- the length of time before the disease begins to worsen -- compared to those receiving lenalidomide and dexamethasone alone. The adverse side effects were similar in intensity and prevalence to those associated with lenalidome and dexamethasone.
Abstract # 727:
- A phase 3 trial of lenalidomide/dexamethasone with elotuzumab (Empliciti™), an antibody therapy that attacks myeloma cells directly and spurs the immune system to launch an attack of its own. Treatment with the three-drug regimen resulted in a 30 percent reduction in the risk that the disease would progress over a three-year period, compared to a course of lenalidomide and dexamethasone alone. Overall, 79 percent of the 321 patients who received the three-drug regimen responded to it, compared to 66 percent of the 325 patients in the two-drug group. The most common adverse side effects were lymphopenia (a condition of abnormally low levels of white blood cells called lymphocytes), neutropenia, blood platelet deficiency, and infection.
"In summary, these encouraging data build upon the real success of our translational efforts in myeloma over the last decade, and provide exciting new options with the real promise of improving patient outcome," said Richardson, who is also the R.J. Corman professor at Harvard Medical School.