Lenalidomide Plus Bortezomib and Dexamethasone (RVD) Produces 100% Response in Multiple Myeloma Patients

New Orleans, LA — Several studies have been examining various 3- and even 4-drug regimens in patients with newly diagnosed multiple myeloma. Paul G. Richardson, MD, and colleagues from the Dana-Farber Cancer Institute in Boston, Massachusetts, conducted a phase I/II study investigated the novel combination of lenalidomide (Revlimid), bortezomib (Velcade), and dexamethasone (Decadron). In an interview with Oncology & Biotech News/Oncology NetGuide, Dr Richardson said response was “unprecedented.” In presenting data from the studies, Dr Richardson said, “Partial responses or better were seen in all of the 66 patients treated with the drug combination…with 74% having a VGPR rate in the phase II portion.” He added that the 54% rate of CR/near CR in patients enrolled in the phase II study “was also encouraging.”

Phase I of the study established the maximum tolerated dose (MTD) as 25 mg of lenalidomide daily, 1.3 mg/m² of bortezomib, and 20 mg of dexamethasone.Patients also received prophylactic anticoagulation therapy. Every single patient who received the RVD regimen responded to the treatment in phase I, with 31% experiencing complete response (CR), 9% having near CR, and 75% having ≥very good partial response (VGPR); toxicities were manageable.

Based on these impressive results, the trial progressed to phase II (N = 35), and data from this clinical trial were presented at the 51^st ASH Annual Meeting. In total, 66 patients in the multi-center study received up to eight 21-day cycles of the RVD regimen. The MTD of lenalidomide was administered on days 1 through 14; bortezomib on days 1, 4, 8, and 11; and 20 mg of dexamethasone during cycles 1 through 4 (10 mg during cycles 5 through 8) on the day of and day after bortezomib administration. A total of 24 patients discontinued therapy, of which 5 (21%) completed treatment per protocol. One-third (n = 8) proceed to autologous stem cell transplant.All patients in the study had partial response (PR) or better, with 54% experiencing CR or nCR response and 69% having ≥VGPR. At 19.3 months follow-up, time to progression (TTP), progression-free survival (PFS), and overall survival (OS) had not yet been reached. The researchers estimated a 76% rate of 1-year TTP and PFS and a 100% rate of OS.

Only 1 patient discontinued because of adverse events. The most common grade 3-4 adverse events (occurring in >1 patient) included lymphopenia (20%), hypokalemia (9%), fatigue (6%), and neutropenia (6%). More than three-quarters of patients (77%) experienced sensory peripheral neuropathy (PNY), with 67% having grade 1 PNY, 30% having grade 2, and only 1 patient experience grade 3 PNY. In addition, one-third of patients experienced grade 1-2 neuropathic and motor PNY. After dose reduction, supportive, care or therapy discontinuation, PNY resolved. Only 2 patients had a thrombolic event.

“The RVD regimen was well tolerated and very active,” Dr Richardson said, noting that it outperformed the current standard for newly diagnosed multiple myeloma patients who have less favorable cytogenetic features, including translocation t4;14, t14;16 and deletion 17p. These patients, said Dr Richardson, typically have a higher risk of treatment failure and death but the RVD regimen was equally effective in patients with and without an adverse cytogenetic profile.

Asked about the implications of these findings, should they be confirmed in planned phase III studies, on the need to undergo autologous stem cell transplant before initiating first-line treatment, Dr Richardson said, “This regimen allows stem cell transplant to be potentially optional.” In 2010, researchers in the United States and France are collaborating on a phase III clinical trial that will be investigating the RVD regimen in 1000 patients, with data expected around 2015. ASH Abstract 1218.