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Blood, 1 October 2006, Vol. 108, No. 7, pp. 2165-2172.
Prepublished online as a Blood First Edition Paper on June 13, 2006; DOI 10.1182/blood-2006-04-019778.
 Previous Article | Next Article 
Submitted April 26, 2006
Accepted May 19, 2006
Bortezomib plus melphalan and prednisone in elderly untreated patients with multiple myeloma: results of a multicenter phase I/II study
Maria-Victoria Mateos, Jose-M Hernandez, Miguel-T Hernandez, Norma-C Gutierrez, Luis Palomera, Marta Fuertes, Joaquin Diaz-Mediavilla, Juan-J Lahuerta, Javier de la Rubia, Maria-Jose Terol, Ana Sureda, Joan Bargay, Paz Ribas, Felipe de Arriba, Adrian Alegre, Albert Oriol, Dolores Carrera, Jose Garcia-Larana, Ramon Garcia-Sanz, Joan Blade, Felipe Prosper, Gemma Mateo, Dixie-Lee Esseltine, Helgi van de Velde, and Jesus-F San Miguel*
Hematology Division, Grupo Espanol de MM (GEM/PETHEMA)
Millennium Pharmaceuticals, Inc., Cambridge, MA, USA
Johnson&Johnson Pharcautical Research&Development, Beerse, Belgium
* Corresponding author; email: sanmigiz{at}usal.es.
Standard first-line treatment for elderly multiple myeloma (MM) patients ineligible for stem cell transplant is melphalan plus prednisone (MP). However, complete responses (CRs) are rare. Bortezomib is active in patients with relapsed MM, including elderly patients. This phase I/II trial in 60 untreated MM patients aged  65 years (half >75 years) aimed to determine dosing, safety, and efficacy of bortezomib plus MP (VMP). VMP response rate was 89%, including 32% immunofixation-negative CR, of whom half of those analyzed achieved immunophenotypic remission (no detectable plasma cells at 10-4 -10-5 sensitivity). VMP appeared to overcome the poor prognosis conferred by retinoblastoma gene deletion and IgH translocations. Results compare favorably with our historical control data for MP, notably response rate (89% vs 42%), event free survival at 16 months (83% vs 51%), and survival at 16 months (90% vs 62%). Side effects were predictable and manageable; principal toxicities were hematologic, gastrointestinal, and peripheral neuropathy, and were more evident during early cycles and in patients aged 75 years. In conclusion, in elderly patients ineligible for transplant, the combination of bortezomib plus MP appears significantly superior to MP, producing very high CR rates, including immunophenotypic CR, even in patients with poor prognostic features.
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