Velcade as Retreatment of Multiple Myeloma Patients Previously Responsive to Velcade.

Velcade (bortezomib, PS 341) represents a novel class of anti-cancer drugs that, according to the randomized phase 3 trial (APEX) including 669 patients with relapsed multiple myeloma (MM), resulted more effective than high-dose dexamethasone as demonstrated by a significant improvement in response rate (43% vs 18%), median time to progression (6.2 vs 3.4 months) and 1-year survival rate (80% vs 67%, respectively). Its use in addition to dexamethasone in patients who had suboptimal responses to velcade alone has been associated with an improvement in responses without prohibitive toxicity, suggesting that the combination of these two drugs can overcome drug resistance. This agent is highly effective on extramedullary plasmacytomas and usually induces a very rapid response (after 1 or 2 cycles), independently of the previous therapies used. To evaluate the possibility of re-inducing a response in relapsed patients previously treated with velcade, we re-treated 3 patients with the same drug at 1.3 mg/m² administered on days 1, 4, 8 and 11 of a 21-day treatment cycle for 8 cycles and dexamethasone 20 mg on the day of and on the day after each velcade dose. The patients (2 females and 1 man) previously treated with velcade as single agent after 47, 54 and 93 months, respectively, from diagnosis and after more than two lines of previous therapy, obtained a very good response without a complete disappearance of the monoclonal component. They were thereafter observed and re-treated with the same drug plus dexamethasone for a relapse documented after 7, 13 and 23 months, respectively. Velcade was well tolerated and the toxicity acceptable, without additional adverse events compared to the first administration. No patient experienced a herpes zoster reactivation and all side effects were typically reversible and disappeared upon drug suspension. Response was very rapid with a >50% decrease of the monoclonal component after 3, 4 and 5 cycles, respectively. It can be hypothesized that velcade, which offers great promise to overcome resistance to conventional chemotherapy, may not be susceptible to the most common drug resistance mechanisms. Based on the chronic nature of MM, drugs with documented efficacy, absence of cumulative toxicities and which do not develop resistance following repeated treatment are required. The responses observed in our relapsed MM patients who received velcade for the second time are encouraging. A longer follow-up and a greater number of patients will conclusively confirm the true efficacy of velcade as re-treatment drug. Updated results on a larger number of treated patients will be available at the time of presentation.