Results of a recent study show that newly diagnosed multiple myeloma patients initially treated with a combination of cyclophosphamide, Velcade, and dexamethasone have better response rates and less severe side effects than patients treated with Revlimid-dexamethasone or cyclophosphamide-Revlimid-dexamethasone.

The survival outcomes for the patients treated with cyclophosphamide, Velcade, and dexamethasone also are promising.

However, the difference in survival rates between the three treatment regimens is not statistically significant.

This is partly because "the numbers [of patients in the study] were too small to show differences in survival,” explained Dr. Craig Reeder of the Mayo Clinic in Scottsdale, Arizona, and one of the authors of the study.

The study compared data from three independent Phase 2 clinical trials, which – according to the study authors – resulted in additional limitations, including a lack of both consistency in control groups and randomization of participants.

Furthermore, the study authors pointed out that the follow-up time was short, leaving no information on longer-term effects. They suggested that further examination of survival outcomes will require a larger Phase 3 study.

Stem cell transplantation using a patient's own stem cells has become a standard treatment option for myeloma patients under the age of 65.

For this reason, it is increasingly necessary to have effective induction therapies - used prior to stem cell harvesting and transplantation - that are not toxic to stem cells.

Previous studies have shown that the combinations of cyclophosphamide ^[1] (Cytoxan) plus Velcade ^[2] (bortezo­mib) and dexa­methasone ^[3] (Decadron) (abbreviated CyBorD), Revlimid ^[4] (lenalidomide) plus dexamethasone (abbreviated RD), and cyclophosphamide plus RD (abbreviated as CRD), are effective as initial therapies for myeloma patients.

According to the study authors, however, there have been no formal comparisons of the efficacy and safety of these three treatment regimens to date.

To make this comparison, researchers from the Mayo Clinic and the University Health Network in Toronto retrospectively analyzed the medical records from 150 newly diagnosed myeloma patients who received one of the three treatments as part of Phase 2 trials in the period from 2004 to 2008.

The median age of the participants was 62.5 years old. Of the 150 patients, 27 percent were defined as high-risk due to genetic abnormalities and 53 percent subsequently received stem cell transplantation.

After four 28-day cycles of treatment, patients who received CyBorD demonstrated greater overall response rates as well as deeper responses than patients receiving the other two combination regimens.

Overall response rates were 89 percent, 88 percent, and 79 percent in the CyBorD, RD, and CRD patient groups, respectively.  These differences were not large enough to be statistically significant.

The differences in depth of response, however, were large enough to be significant.

Patients in the CyBorD group had a combined complete and near complete response rate of 41 percent, and a very good partial response rate of 24 percent.  This compares to 12 percent and 23 percent, respectively, for patients who received the RD regimen, and 2 percent and 28 percent for patients treated with the CRD regimen.

Survival measures were similar across all three treatment groups. The progression-free survival times for CyBorD, RD, and CRD were 2.7 years, 3.2 years, and 2.3 years, respectively, with a median progression-free survival of 2.6 years for all patients.

The three-year overall survival rates by treatment group were 88 percent, 88 percent, and 79 percent, respectively, for the CyBorD, RD, and CRD groups. For all 150 patients, the median four-year overall survival was 80 percent.

Transplanted patients had a higher three-year overall survival rate (95 percent) compared to patients who did not receive a transplant (75 percent).

Trial participants categorized as high-risk relapsed earlier than standard-risk patients, with a median progression-free survival of 2.1 years and 2.7 years, respectively.

Participants receiving CyBorD showed lower rates of either severe or life-threatening side effects (33 percent and 8 percent, respectively) than those receiving RD (50 percent and 6 percent, respectively) or CRD (49 percent and 25 percent, respectively).

However, the CyBorD group had higher rates of peripheral neuropathy (59 percent) than both the RD group (21 percent) and CRD group (15 percent).  Peripheral neuropathy is numbness or tingling, typically in the hands or feet, that can occur as a side effect of myeloma treatment.

According to Dr. Reeder, further studies of these combination therapies in post-stem cell transplantation treatment are planned.

For more information, please see the study in the British Journal of Haematology ^[5] (abstract).