The findings of a new study suggest that a combination regimen of Velcade (bortezomib), thalidomide (Thalomid), and prednisone, abbreviated as VTP, is as effective as the standard combination of Velcade, melphalan (Alkeran), and prednisone, abbreviated as VMP, in the treatment of elderly patients with multiple myeloma. The trial also discovered that the addition of maintenance therapy led to increased response rates. Researchers presented their Phase 3 study results at the American Society of Hematology’s (ASH) 51st annual meeting in December.

While VMP without maintenance therapy currently is one of the standard treatments for elderly patients with newly diagnosed myeloma, the availability of new drugs has motivated researchers to search for more effective, less toxic combination treatments. In another study, also presented at the ASH 2009 conference, the addition of thalidomide to the VMP regimen, followed by maintenance therapy, resulted in greater response rates than VMP (see related Beacon news).

In this Phase 3 study, researchers compared VTP and VMP as induction therapies as well as Velcade-thalidomide (VT) and Velcade-prednisone (VP) as maintenance therapies, evaluating both efficacy and side effects of the combination therapies.

Researchers recruited 260 patients and randomly assigned them to either the VTP or VMP treatment group. In the VMP treatment, patients received 1.3 mg/m² of Velcade on days 1, 4, 8, 11, 22, 25, 29, and 32 of one six-week cycle, and then on days 1, 8, 15, and 22 of five five-week cycles. Melphalan, 9 mg/m² and prednisone, 60 mg/m² were given on days 1-4 of each of the six cycles. In the VTP treatment, patients received Velcade and prednisone at the same dosage and schedule, and 100 mg of thalidomide daily.

Maintenance therapy consisted of a three-month cycle of 1.3 mg/m² Velcade given on days 1, 4, 8, and 11, and either 50 mg of thalidomide daily (VT) or 50 mg of prednisone every other day (VP) for up to three years. Patients were randomly assigned to the two treatment options.

Of the 260 patients, 253 were included in the final analysis – 125 in the VMP group and 128 in the VTP group. Both treatments resulted in similar rates of at least partial response or better – 81 percent in the VMP group and 79 percent in the VTP group. Twenty-two percent of VMP patients and 27 percent of VTP patients achieved complete response, for an average of 25 percent.

Researchers did not observe any significant differences between the VMP and VTP groups in progression-free survival rates (71 percent versus 61 percent) or overall survival rates (81 percent versus 84 percent). In each treatment group, two patients experienced disease progression.

Of the 178 patients who participated in maintenance therapy, 143 were included in the final analysis. The addition of maintenance therapy increased the rate of complete response from 25 percent to 42 percent in both treatment groups. Both VT and VP maintenance resulted in similar overall survival rates after one year (92 percent versus 89 percent, respectively).

Out of 27 patients who exhibited high-risk genetic abnormalities, 26 percent achieved complete response after induction and 42 percent after maintenance. Both response rates were similar to the overall patient response, indicating that the maintenance regimens successfully combated the negative prognosis associated with patients’ genes.

Researchers observed differences in side effects between the two induction therapies. More patients in the VMP group than in the VTP group experienced decreased white blood cell counts, or neutropenia (37 percent versus 21 percent), and infection (7 percent versus <1 percent). However, eight VTP patients (5 percent) experienced serious heart problems not observed in any VMP patients. Nine percent of VTP patients also experienced peripheral neuropathy (nerve damage in the limbs), compared to five percent of VMP patients.

In both maintenance therapies, patients experienced few severe side effects. Two patients in the VT group and one patient in the VP group had severe heart problems, and four patients in the VT group and one patient in the VP group had severe gastrointestinal problems.

Researchers concluded that VMP and VTP work equally well as induction therapies. They added that the addition of VT or VP as maintenance therapies to VMP and VTP offer clear benefits by increasing response without compromising side effects..

For more information, see abstract 3 at the ASH meeting Web site.