A follow-up analysis of recent trial results suggests that reducing Velcade administration from twice weekly to once weekly when given in combination with melphalan, prednisone, and thalidomide reduces side effects in elderly multiple myeloma patients.  The less frequent administration did not affect the efficacy of the treatment.

The researchers had reported earlier this summer that the addition of thalidomide (Thalomid) to Velcade (bortezomib), melphalan (Alkeran), and prednisone (referred to as VMPT), followed by long-term treatment with Velcade and thalidomide (VT), improved response rates and progression-free survival in elderly multiple myeloma patients compared to the current standard of care (see related Beacon news).

However, the researchers had to lower the Velcade dosage from a twice-weekly infusion to once-weekly because many patients discontinued treatment due to side effects, in particular peripheral neuropathy (nerve damage to the extremities that can cause pain and tingling sensations).

A total of 511 newly diagnosed multiple myeloma patients over the age of 65 were included in the study.  Of these patients, 139 received 1.3 mg/m² of Velcade twice a week before the researchers switched to once weekly dosing. The remaining 372 received 1.3 mg/m² of Velcade once weekly from the time of treatment initiation.

In their retrospective analysis, the researchers evaluated the impact of the reduced dosing schedule on patient outcomes and side effects. They were particularly interested in finding out if the once-weekly dosing schedule had an impact on the rate of peripheral neuropathy and treatment discontinuation.

The researchers found that there were no significant differences in response rates between patients receiving once- or twice-weekly Velcade.  Eighty-five percent of patients receiving once-weekly Velcade achieved a partial response or better, compared to 86 percent of patients receiving a twice-weekly dose.

The median progression-free survival time for patients receiving once-weekly Velcade was 33.1 months, compared to 31.7 months for patients receiving twice-weekly Velcade.

The three-year overall survival was also similar between the two treatment groups. Eighty-eight percent of patients in the once-weekly treatment group were alive three years after diagnosis, compared to 89 percent of patients in the twice-weekly treatment group.

The researchers explained that the reduction in Velcade dosage allowed patients to remain on treatment longer.  The average cumulative Velcade dose was similar between the two groups, resulting in similar efficacy.

Patients in the once-weekly Velcade treatment group received a median cumulative dose of 39.4 mg/m²_, which was similar to the 40.1 mg/m² median cumulative Velcade dose that patients received in the twice weekly treatment group.

Side effects related to reduced blood cell and platelet levels were similar between the treatment groups. The risk of severely low platelet levels was slightly lower in patients receiving Velcade once weekly.

However, the occurrence of side effects not related to blood cell counts was significantly lower in the once-weekly Velcade treatment group (35 percent) than in the twice-weekly Velcade treatment group (51 percent).

Most pronounced were differences in peripheral neuropathy between the two treatment groups. Eight percent of once-weekly treated patients experienced severe nerve damage, as opposed to 28 percent of those treated twice a week.

Of those patients treated with Velcade once a week, only 5 percent could not complete their full treatment schedule due to the severity of their nerve damage, as compared to 15 percent of those treated twice weekly.

Fewer patients in the once-weekly treatment group (17 percent) needed Velcade dose reductions due to nerve damage than patients in the twice-weekly treatment group (41 percent).

The rate of improvement or resolution of the treatment-induced nerve damage after completion of treatment in patients with moderate to severe nerve damage was similar between the two treatment groups (64 percent and 66 percent, respectively).

For more information, see the study in the journal Blood (abstract).