A combination regimen of Velcade ^[1] (bortezomib), Doxil ^[2] (pegylated liposomal doxorubicin), and dexamethasone ^[3] (Decadron), known as the VDD regimen, followed by Revlimid ^[4] (lenalidomide) after autologous stem cell transplantation (ASCT) is an effective therapy for untreated multiple myeloma patients, according to a study recently published in the Journal of Clinical Oncology.

Velcade is a highly active therapeutic agent in multiple myeloma patients. It suppresses tumor growth by inhibiting the enzymes that break down critical proteins in cancerous cells. Although Velcade is approved as a single agent, previous studies have suggested that the Velcade and Doxil combination is more potent than Velcade alone.

The Myeloma Beacon previously reported results ^[5] from a Phase 2 clinical trial that evaluated the VDD regimen as initial therapy, also known as induction therapy, before ASCT in newly diagnosed myeloma patients, but unlike this study, it did not include post-transplantation therapy. A high rate of complete response was observed.

In addition to evaluating the efficacy of the VDD regimen, the current study investigated if post-transplantation therapy with Revlimid improved response rates. Revlimid was selected for post-transplantation therapy because it is a less toxic and more potent alternative to thalidomide ^[4] (Thalomid). Post-transplantation therapy with thalidomide improved progression-free survival rates in several randomized trials; however, a recent trial observed that thalidomide was only beneficial in patients who achieved less than a very good partial response after induction therapy.

The current study enrolled 102 elderly myeloma patients. Each patient received induction therapy consisting of four 21-day cycles of Velcade (1.3 mg/m² on days 1, 4, 8, and 11), Doxil (30 mg/m² on day 4), and dexamethasone (40 mg/day; cycle 1: days 1 to 4, 8 to 11, and 15 to 18; cycles 2 to 4: days 1 to 4). Patients then underwent ASCT with melphalan ^[6] (Alkeran), followed by four 28-day cycles of Revlimid (25 mg/day on days 1 to 21) and prednisone (50 mg every other day). Patients then received a lower dose of Revlimid (10 mg/day on days 1 to 21) until relapse.

After induction with the VDD regimen, 58 percent of patients achieved a very good partial response or better, including 13 percent with complete response. Following ASCT with melphalan, 82 percent of patients achieved a very good partial response or better, including 38 percent with complete response. These numbers improved to 86 percent with a very good partial response or better and 66 percent with complete response following post-transplantation therapy with Revlimid. The two-year progression-free survival rate was 69 percent, and the two-year overall survival rate was 86 percent.

The most severe side effects during the VDD treatment included decreased platelet count (17 percent), nerve damage in the limbs (16 percent), decreased white blood cell count (10 percent), pneumonia (10 percent), and treatment-related mortality (3 percent).

During post-transplantation Revlimid therapy, the most severe side effects were decreased white blood cell count (16%), decreased platelet count (6%), pneumonia (5%), and skin rashes (4%).

Based on the results, the authors of the study concluded that sequential treatment with VDD, melphalan-based ASCT, and post-transplantation therapy with Revlimid is a highly effective treatment regimen for patients receiving ASCT.

The authors recommended that further testing be done in randomized Phase 3 trials. They added that the VDD regimen should also be compared to other induction regimens. According to Dr. Antonio Palumbo, principle investigator of the study, there are currently no studies in progress that compare Velcade-based versus Revlimid-based initial therapy or thalidomide-based versus Revlimid-based post transplantation therapy.

For more information, please read the original study in the Journal of Clinical Oncology ^[7] (abstract).