The combination regimen of Revlimid (lenalidomide), melphalan (Alkeran), prednisone, and thalidomide (Thalomid), abbreviated RMPT, is an active and safe therapy for multiple myeloma patients who have relapsed or who are resistant (refractory) to previous myeloma treatment. The findings were published recently in the journal Leukemia.

Although melphalan-prednisone (MP) combination has been a standard therapy in multiple myeloma for the last thirty years, the introduction of novel agents, such as Revlimid, thalidomide and Velcade, has significantly improved response rates and extended remission in patients with refractory and relapsed myeloma. Revlimid and thalidomide are from the same class of drugs (immunomodulatory agents), and each drug has already been shown to increase the effectiveness of MP therapy.

In their study, the researchers evaluated the tolerability and effectiveness of MP treatment in combination with both Revlimid and thalidomide in relapsed/refractory myeloma patients. The Phase 2 trial included a total of 44 patients at six testing centers in Italy. Twenty-six patients received RMPT as second-line therapy and 18 as third-line therapy.

Patients received six 28-day cycles of Revlimid (10 mg on days 1 to 21), melphalan (0.18 mg/kg on days 1 to 4), prednisone (2 mg/kg on days 1 to 4), and thalidomide (either 50 mg or 100 mg on days 1 to 28). In addition, patients took 100 mg of aspirin daily to prevent blood clots. Twenty-two patients did not complete the six cycles, due to disease progression (9 patients), side effects (9 patients), or withdrawal of consent (4 patients). The 22 patients who completed the six cycles received maintenance therapy with 10 mg of Revlimid on days 1 to 21 of a 28-day cycle.

Out of the 44 total patients, 75 percent responded to the treatment, including 32 percent achieving a very good partial response and 2 percent achieving a complete response. Out of the 22 patients who received 100 mg of thalidomide daily with RMPT, 77 percent responded to the treatment, including 41 percent achieving at least a very good partial response.

Researchers reported a one-year progression-free survival rate of 51.5 percent and a one-year overall survival rate of 72 percent. A total of ten patients died during the study, six from disease progression and four from side effects.

The most common life-threatening side effects reported were low white blood cell count, which affected 18 percent of the study participants; low platelet count (7 percent); and infection (7 percent). Of the four patients who died during treatment from side effects, three died from infections (pneumonia, septic shock, and meningitis) and one died suddenly, from a cause unrelated to myeloma.

The most common severe side effects reported were low white blood cell count (45 percent), anemia (32 percent), low platelet count (27 percent), pneumonia (7 percent), fatigue (7 percent), and low white blood cell count accompanied by a fever (4.5 percent).

The majority of severe to life-threatening side effects developed during the first three cycles of therapy. More of these side effects occurred in patients who received RMPT as a third-line therapy compared with second-line therapy.

Based on these results, the authors of the study concluded that RMPT therapy is highly active in patients with relapsed and/or refractory myeloma. However, they questioned whether it is preferable to administer sequential single-agent therapy with fewer side effects or a more complex combination therapy with more side effects but higher reported response rates.

“A combination approach might be considered at diagnosis when there is the best chance to induce a prolonged remission duration. A sequential approach with a less intensive regimen should be considered during subsequent relapses, when the risk of toxicity is increased,” the authors of the study wrote in their concluding statements of the article.

The authors also noted that RMPT, which is an oral treatment, might be preferable for those patients who cannot make frequent clinic visits for treatments requiring intravenous medication.

The authors suggested additional studies to further evaluate RMPT as a treatment for multiple myeloma.

For more information, please read the original article in the journal Leukemia (abstract).