At the 57th American Society of Hematology ( ASH ) Annual Meeting and Exposition in Orlando, investigators at Dana-Farber Cancer Institute have presented 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.

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) A combined phase 1 and phase 2 trial ha assessed Lenalidomide / Dexamethasone plus Daratumumab ( Darzalex ), a human IgG1k monoclonal antibody that binds with high affinity to the CD38 molecule. 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%.
In 93% 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, muscle spasms, cough, diarrhea, fatigue, and hypertension.

B) A phase 3 trial has evaluated Lenalidomide / Dexamethasone plus Ixazomib ( Ninlaro ), a proteasome inhibitor that blocks the action of proteasomes. The FDA ( 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% improvement in progression-free survival, compared to those receiving Lenalidomide and Dexamethasone alone.
The adverse side effects were similar in intensity and prevalence to those associated with Lenalidomide and Dexamethasone.

C) In a phase 3 trial, the combination of Lenalidomide / Dexamethasone with Elotuzumab ( Empliciti ), an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 ( SLAMF7 ), was evaluated. Treatment with the three-drug regimen resulted in a 30% 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% of the 321 patients who received the three-drug regimen responded to it, compared to 66% of the 325 patients in the two-drug group.
The most common adverse side effects were lymphopenia, neutropenia, blood platelet deficiency, and infection.

Source: Dana Farber Cancer Institute, 2015

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