The results of a recent study from Italy suggest that the combination treatment of melphalan, prednisone, and thalidomide may increase survival in newly diagnosed elderly multiple myeloma patients compared to melphalan and prednisone alone. However, the rate of side effects increased with the addition of thalidomide.

Despite the higher rate of side effects, the study authors suggested that the combination of melphalan (Alkeran), prednisone, and thalidomide (Thalidomid) (MPT) should be considered a standard of care for newly diagnosed patients who are over 65 years old or ineligible for a stem cell transplant.

According to the Italian researchers, previous trials that compared the efficacy of MPT versus melphalan-prednisone (MP) have given variable results. All of these studies showed an increase in patient response; however, not all studies showed improvements in overall survival (see related Beacon news).

To shed more light on the issue, the Italian researchers conducted a clinical trial that compared MPT versus MP in 118 newly diagnosed multiple myeloma patients over the age of 65 who were ineligible for stem cell transplantation.

All patients received 0.25 mg/kg of melphalan and 60 mg/m² of prednisone orally for four days, every 28 days, for a maximum of 48 weeks. Thalidomide was given at 100 mg daily for 48 weeks. Patients who did not completely respond to treatment after six cycles had the option to be treated for six additional cycles.

As in previous studies, the researchers observed a better overall response rate in patients receiving MPT (87 percent) than in patients receiving MP (47 percent). In particular, 20 percent of patients receiving MPT achieved a complete response, compared to 7 percent of patients receiving MP.

After a median follow-up of 30 months, the progression-free survival was 33 months for patients receiving MPT, compared to 22 months for patients receiving MP.

Overall survival for patients receiving MPT was 52 months, compared to 32 months for patients receiving MP. However, the study authors pointed out that the difference in overall survival between the two groups was not large enough to be significant.

The researchers observed an increased rate of side effects in patients receiving MPT.  The most common side effect was low white blood cell counts, which was seen in 28 percent of MPT-treated patients and 13 percent of MP patients.  The rate of infection was also higher in MPT patients (9 percent) compared to MP patients (2 percent).  Both side effects led to a delay in treatment for 30 percent of patients.

Other common side effects included deep vein thrombosis (11 percent in MPT patients versus 0 percent in MP patients), nerve damage in the extremities (6 percent in MPT patients versus 0 percent in MP patients), and constipation (17 percent for MPT patients versus 6 percent for MP).

An ongoing, related Phase 3 trial is comparing MPT to the combination of Revlimid (lenalidomide) and low-dose dexamethasone (Decadron), another standard of care for newly diagnosed elderly or transplant ineligible myeloma patients.  This trial is being sponsored by Celgene, the pharmaceutical company that markets Revlimid and thalidomide, and is being conducted at centers throughout the world.  It is currently recruiting participants.

For more information, please see the study in Leukemia and Lymphoma (abstract).