Four-drug regimen ups response, progression-free survival in older multiple myeloma patients

NEW ORLEANS—More is better, at least when it comes to treatments for multiple myeloma. Studies from Spanish and Italian investigators showed that upfront use of four drugs improves durable responses and progression-free survival in elderly patients. Both ASH 2009 studies also showed that a kinder, gentler weekly schedule of bortezomib(Drug information on bortezomib) (Velcade) instead of the standard twice-weekly schedule maintains efficacy and reduces toxicity.

Yes to weekly bortezomib

Using melphalan instead of thalidomide(Drug information on thalidomide) as part of a modified-intensity three-drug combination with bortezomib/prednisone reduces toxicity without compromising efficacy in elderly patients (n = 260) with multiple myeloma, according to results of a prospective, multicenter, randomized phase III trial. In this study, the modified-intensity regimens were bolstered by maintenance therapy.

Although melphalan(Drug information on melphalan) causes more neutropenia, the cardiac toxicity seen with thalidomide is more difficult to manage, said lead author Maria-Victoria Mateos, MD, PhD, from Hospital Universitario de Salamanca in Spain. Neutropenia can be managed with growth factor support.

No grade 3 cardiac events occurred in the melphalan arm, while 8.5% of those in the thalidomide induction arm had grade 3 cardiac events (five cardiac failure, two atrial fibrillation, two hypotension, one heart attack, one atrioventricular block).

Six cycles of both modified induction regimens—bortezomib/melphalan/prednisone (VMP) and bortezomib/thalidomide/prednisone (VTP)—were equally effective at a median follow up of 22 months for time to progression and progression-free survival. Overall survival was also similar: 81% for VMP vs 84% for VTP. Outcomes were the same in high-, intermediate-, and low-risk groups (abstract 3).

An important aspect of this study was the use of weekly bortezomib for induction therapy for cycles 2 through 6, instead of the standard twice-weekly schedule. “This study showed that the answer is ‘yes’ to weekly bortezomib,” Dr. Mateos said.

Patients (n = 178) were randomized to maintenance therapy with bortezomib/thalidomide or bortezomib/prednisone for up to three years. Overall, maintenance therapy increased the complete response rate from 25% to 42%, but there were no significant differences between the two groups. Maintenance therapy reduced toxicities, especially peripheral neuropathy, she said.

A prospective, randomized, phase III Italian study in a similar population of elderly patients with newly diagnosed multiple myeloma (n = 511) showed that induction therapy with a four-drug combination of bortezomib, melphalan, prednisone(Drug information on prednisone), and thalidomide (VMPT) followed by maintenance therapy with bortezomib and thalidomide (VT) achieved results comparable to those of the Spanish study (abstract 128).

“Both studies used four drugs. In our study, we used them up front and in the Spanish study, a three-drug combination was followed by a fourth drug for maintenance therapy,” explained lead author Antonio Palumbo, MD, University of Torino, A.O.U. San Giovanni Battista, Torino, Italy. This study showed that VMPT with VT maintenance was superior to VMP alone.