For elderly myeloma patients or patients ineligible for a stem cell transplant, a traditional frontline therapy has been the “MP” combination of the chemotherapy drug melphalan and the corticosteroid prednisone.

Recent clinical trials, however, have combined highly effective, newer treatments such as Velcade (bortezomib), thalidomide (Thalomid), and Revlimid (lenalidomide) with the standard MP regimen in the hope of finding improved response and survival rates.

This Monday at the 50th annual meeting of the American Society of Hematology (ASH), researchers presented updated results of a Phase 3 clinical trial comparing the Velcade, melphalan, and prednisone (VMP) treatment combination to the traditional MP regimen for newly diagnosed myeloma patients.

The multi-national trial – dubbed VISTA (“Velcade as Initial Standard Therapy in Multiple Myeloma: Assessment with Melphalan and Prednisone”) – involved over 600 patients.

The trial found that the VMP combination was more effective compared to MP in regard to all key efficacy measures: response rate, time to progression, time to subsequent therapy, and overall survival.

Three-year survival rates for the VMP and MP regimens were 72 percent and 59 percent, respectively. Time to subsequent therapy was significantly longer in the VMP treated patients, 28.1 months versus 19.2 months for the MP patients. Likewise, only 38 percent of the patients treated with VMP required subsequent therapy, versus 57 percent for the MP treated patients.

These results for the VMP regimen are similar to those found in a 2006 clinical trial assessing the thalidomide, melphalan, and prednisone (TMP) combination. In that trial, newly diagnosed patients receiving the TMP regimen had a three-year survival rate of 80 percent.

In the VISTA trial, patients requiring subsequent therapy were treated with either Velcade alone or a Velcade combination, a Revlimid (lenalidomide) combination, or a thalidomide (Thalomid) combination. The combinations consisted of multiple drugs, including dexamethasone, added to the primary therapy.

Among the patients initially treated with VMP, subsequent treatment with Velcade (alone or in combination) led to a complete response in 6 percent of the cases and a partial response in 33 percent of the cases. For the VMP patients subsequently receiving either Revlimid or thalidomide combination treatments, the complete and partial response rates were, respectively, 4 percent and 52 percent (Revlimid), and 4 percent and 44 percent (thalidomide)

A common side effect of the initial VMP regimen was peripheral neuropathy (pain or numbness in the hands or feet). It was experienced by 47 percent of the VMP patients versus 5 percent of the MP patients. The cases of peripheral neuropathy in the VMP patients improved or resolved themselves 79 percent of the time, within a median 1.9 months. Sixty percent of the neuropathy cases resolved themselves completely, within a median of 5.7 months.

Researchers also presented on Saturday at the ASH meeting their findings on the safety and effectiveness of VMP and MP in VISTA patients with renal impairment.

Renal impairment – the inability of the kidneys to function properly – is a frequent complication of multiple myeloma, and it is associated with poorer treatment outcomes.

The safety profiles for VMP and MP were similar among the VISTA patients with renal impairment. However, 44 percent of the patients treated with VMP experienced a reversal of their renal impairment, versus 34 percent of MP-treated patients. Time to reversal of renal impairment was also shorter for VMP treated patients – 2.1 months versus 2.4 months.

Patients treated with VMP who achieved reversal of renal impairment also showed a longer one-year survival rate – 90 percent compared to 81 percent for MP patients.

For more information, see the ASH meeting abstract 650 and associated press release (overall VISTA trial update) and ASH abstract 1727 (safety and effectiveness of VMP in VISTA patients with renal impairment.)