Melphalan Better Partner With Bortezomib for Older Patients With Untreated Multiple Myeloma: Presented at ASH
By Ed Susman
NEW ORLEANS -- December 7, 2009 -- Combining melphalan, rather than thalidomide, to a bortezomib-based regimen is as effective and less toxic for older patients with untreated multiple myeloma, researchers said here at the American Society of Hematology (ASH) 51st Annual Meeting and Exposition.
“In the melphalan group, there was more neutropenia and the possibility of infections,” said Maria-Victoria Mateos, MD, Hospital Universitario de Salamanca, Salamanca, Spain, on December 5. However, cardiac toxicity seen among patients receiving the thalidomide combination “was more difficult to treat” than neutropenia, which can be prevented or controlled.
The study included 260 patients (mean age, 65 years) who were randomised to 6 cycles of bortezomib plus melphalan and prednisone or bortezomib plus thalidomide and prednisone as induction therapy followed by maintenance with bortezomib plus thalidomide or bortezomib plus prednisone for up to 3 years.
During the induction phase, 37% of patients in the melphalan arm experienced grade 3 neutropenia compared with 21% of patients in the thalidomide arm. Seven percent of melphalan-treated patients developed grade 3 infections, compared with <1% of thalidomide-treated patients.
About 8.5% of patients receiving thalidomide in the induction phase experienced grade 3 cardiac events, including 5 episodes of cardiac failure, 2 cases of atrial fibrillation, 2 cases of hypotension, 1 myocardial infarction, and 1 atrioventricular block. No grade 3 cardiac events were reported in patients receiving melphalan.
Peripheral neuropathy was reported in 5% of the melphalan-treated patients and 9% of thalidomide-treated patients.
During maintenance therapy, the most relevant grade 3 toxicities included cardiac events in 2 thalidomide-treated patients and 1 in a patient receiving prednisone.
In the bortezomib/melphalan/prednisone group, patients available for evaluation received bortezomib 1.3 mg/m2 twice weekly for one 6-week cycle, followed by once weekly cycles for 5 five-week cycles in combination with oral melphalan 9 mg/m2 and prednisone 60 mg/m2 once daily on days 1 to 4 of each cycle.
In the thalidomide arm, patients received the same bortezomib and prednisone regimens, but instead of melphalan they received thalidomide at a dose of 100 mg daily.
Response rate to induction therapy was similar in both arms with an overall response rate of 80% in the melphalan arm and 81% in the thalidomide arm. Only 2 patients progressed under induction treatment in each arm.
Following the 6 induction cycles, patients moved into maintenance, consisting of a conventional cycle of bortezomib 1.3 mg/m2 twice weekly, administered every 3 months in combination with either continuous thalidomide 50 mg daily or prednisone 50 mg on alternate days.
After a median follow-up of 22 months, there were no significant differences in either time to progression (75% in the melphalan arm vs 70% in the thalidomide arm), progression-free survival (melphalan, 71% vs thalidomide, 61%), or overall survival (melphalan, 81% vs thalidomide, 84%).
Maintenance therapy appeared to reduce toxicities, especially peripheral neuropathy.
[Presentation title: A Prospective, Multicenter, Randomized, Trial of Bortezomib/Melphalan/Prednisone (VMP) versus Bortezomib/Thalidomide/Prednisone (VTP) as Induction Therapy Followed by Maintenance Treatment With Bortezomib/Thalidomide (VT) versus Bortezomib/Prednisone (VP) in Elderly Untreated Patients with Multiple Myeloma Older Than 65 Years. Abstract 3]
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