Results from an Italian Phase 1/2 trial show that a combination therapy consisting of lower doses of Velcade, melphalan, and prednisone may be an effective and safe salvage therapy for older multiple myeloma patients.

Over half of the patients in the trial responded to the treatment, and according to the study investigators, the treatment was well tolerated, making it a viable treatment option for older myeloma patients.

In Europe, the combination treatment of Velcade (bortezomib), melphalan (Alkeran), and prednisone – commonly referred to as VMP – is often given as initial therapy to newly diagnosed multiple myeloma patients who are not eligible for stem cell transplantation.

However, according to the Italian researchers, many patients experience severe side effects with VMP treatment and eventually discontinue treatment due to the side effects.

Subsequent trials involving lower doses of Velcade have shown an improvement in the safety profile without a reduction in the efficacy of the regimen.

In the current study, the investigators sought to determine the efficacy and safety of VMP as salvage therapy in older multiple myeloma patients. Salvage therapy refers to treatment for myeloma patients who are refractory to their first treatment or who relapse after prior treatment.

The researchers point out that older patients frequently need dose-adjusted treatments because of the presence of other diseases and poorer overall health.

They therefore used a new, lower-dose VMP regimen in their study.

Between March 2008 and February 2010, the investigators recruited 42 elderly patients with relapsed or refractory myeloma.

The median patient age was 73 years. The median time from diagnosis to the start of VMP treatment was 40 months.

Overall, 74 percent of the patients had received one prior line of therapy, and 26 percent had received two prior lines of therapy.

The patients received 2 mg of melphalan three times a week, 1.3 mg/m² of Velcade once a week, and 50 mg of prednisone every other day throughout a 28-day treatment cycle.  Patients received a total of nine cycles, unless side effects forced them to stop treatment.

The median follow-up time was 21.1 months.

The researchers found that 57 percent of patients had a partial response or better to treatment. The researchers described this response rate as consistent with rates from other studies involving relapsed patients.

The median time to disease progression was 18 months, and the progression-free survival rate at 37 months was 21 percent.

The median overall survival was 30 months.

According to the researchers, VMP had an acceptable safety profile.

Severe side effects were observed in 38 percent of the patients and included low platelet counts (23 percent) and infections (12 percent). The researchers point out that severe side effects were more common during earlier treatment cycles.

Peripheral neuropathy (pain, tingling, or loss of sensation in the extremities), a common Velcade-related side effect, was observed in 33 percent of patients.

The most common causes of death included disease progression (38 percent), infections (5 percent), acute heart failure (2 percent), and fluid accumulation in the lungs (2 percent).

For more information, please see the study in Cancer (abstract).