Preliminary results from a Phase 1 clinical trial suggest that everolimus (RAD001), in combination with Revlimid (lenalidomide), may have potential in the treatment of relapsed/refractory multiple myeloma. The findings were presented on June 4 at the American Society of Clinical Oncology (ASCO) annual meeting.

Everolimus is marketed by Novartis under the brand name Afinitor for the treatment of advanced kidney cancer and under the name Zortress to prevent kidney transplant rejection.  Everolimus is currently being investigated as a potential treatment for multiple myeloma, and often goes by the codename RAD001 in clinical trial descriptions. The drug has not shown any anti-myeloma effects as a single agent. However, previous studies have shown that drugs similar to everolimus in combination with Revlimid may be effective against myeloma.

In their study, researchers sought to determine whether the combination of everolimus with Revlimid would have anti-myeloma effects.

The trial enrolled 28 patients who received varying doses of the oral combination treatment for 21 days with a 7-day rest period. All patients had previously experienced either relapse, meaning they became more ill after a partial recovery from multiple myeloma, or were refractory, meaning they did not respond to the most recent treatment they were given.

Patients received treatment until disease progression or unacceptable levels of side effects were observed.

Data from 26 patients were analyzed. Nineteen of the patients had completed two treatment cycles at the time of analysis.

Researchers observed at least a minor response in 63 percent of the patients who had completed two treatment cycles. One patient reached stable disease.

Eleven percent of patients experienced severe low white blood cell counts (neutropenia), and 22 percent of patients experienced severe low platelet counts (thrombocytopenia). These side effects were severe enough that they limited the dosing of the drug. Researchers reported 5 mg of everolimus and 15 mg of Revlimid as the maximum tolerated dose.

The most common mild to moderate side effects included nausea, fatigue, shortness of breath, diarrhea, constipation, tingling or numbness in fingers and toes (peripheral neuropathy), and muscle cramps.

Researchers concluded that the treatment was well-tolerated and may provide a non-steroid based treatment alternative for relapsed/refractory multiple myeloma patients.  However, Dr. Robert Z. Orlowski of the MD Anderson Cancer Center described the results as “mixed,” given the neutropenia and peripheral neuropathy observed in the trial participants.

Researchers suggested further testing of the combination treatment in Phase 2 trials.

For more information, please see abstract 8032 at the ASCO Meeting website.