On May 31 at the 45th meeting of the American Society for Clinical Oncology (ASCO), researchers from Italy will report the results for a Phase 3 study currently comparing the combination Velcade ^[1] (bortezomib)–melphalan ^[2] (Alkeran)–prednisone ^[3]–thalidomide ^[4] (Thalomid) (VMPT) to Velcade-melphalan-prednisone (VMP) for the treatment of elderly, newly diagnosed myeloma patients.

Overall, the very good partial response rate for patients treated with VMPT was 55 percent, compared to 45 percent for those treated with VMP. After a median follow-up time of 14.5 months, the three-year progression-free survival was 74 percent in the VMPT group and 70 percent in the VMP group. The three-year overall survival was similar between the two groups – 88 percent for those treated with VMPT, and 87 percent for those treated with VMP.

This clinical trial for newly diagnosed patients came after the same four-drug combination was shown to induce a high percentage of complete responses in relapsed and refractory patients. In a Phase 1/2 trial, the complete response rate was 17 percent and the very good partial response rate was 27 percent.

Patients were treated with nine five-week cycles of the therapy combinations. Of the 500 patients in the study, 354 who received at least one cycle of treatment were evaluated.

Subgroup analyses did not show any statistical differences between the response rates and progression-free survival rates of the two groups in regard to either chromosomal abnormalities or disease stage. However, the researchers point out that both regimens appear to yield good responses in patients with a poor prognosis (based on disease stage) and those with high-risk chromosomal abnormalities.

Age, however, was associated with lower very good partial response rates for patients older than 75 years of age treated with VMPT. The same association was not observed for those treated with VMP.

Similarly, age (patients < 75 years old) and achievement of a very good partial response were indicative of longer progression-free survival for VMPT-treated patients, but not for patients treated with VMP.

The frequency of serious or life-threatening adverse side effects (Grade 3-4) was similar between the two groups, with those treated with VMPT experiencing slightly higher incidences.

The most frequent Grade 3-4 side effect was neutropenia, experienced by 36 percent versus 31 percent of patients for VMPT and VMP treatment groups, respectively. Neutropenia, a lack of immune system-boosting white blood cells, can cause serious infections. Thrombocytopenia was observed in 20 percent of VMPT-treated patients versus 19 percent of VMP-treated patients. The low blood platelet counts found in patients suffering from thrombocytopenia leads to decreased blood clotting functions that stop blood loss.

Peripheral neuropathy, which can cause debilitating pain and numbness in hands and feet that can potentially be permanent, was observed in 18 percent versus 12 percent of patients for the two groups. Finally, infections were 14 percent versus 10 percent for VMPT versus VMP, respectively.

While the researchers are positive in regards to the enhanced response rates for the four-drug regimen, they state that a longer follow-up time is needed to access the full effects on both progression-free survival and overall survival.

For more information, please see abstract 8515 ^[5] at the 2009 ASCO meeting ^[6] Web site.