Sequential vs alternating administration of VMP and Rd in elderly patients with newly diagnosed MM.
Bortezomib plus melphalan and prednisone (VMP) and lenalidomide plus low-dose dexamethasone (Rd) are 2 standards of care for elderly untreated multiple myeloma (MM) patients. We planned to use VMP and Rd for 18 cycles in a sequential or alternating scheme. Patients (233) with untreated MM, >65 years, were randomized to receive 9 cycles of VMP followed by 9 cycles of Rd (sequential scheme; n = 118) vs 1 cycle of VMP followed by 1 cycle of Rd, and so on, up to 18 cycles (alternating scheme; n = 115). VMP consisted of one 6-week cycle of bortezomib using a biweekly schedule, followed by eight 5-week cycles of once-weekly VMP. Rd included nine 4-week cycles of Rd. The primary end points were 18-month progression free survival (PFS) and safety profile of both schemes. The 18-month PFS was 74% and 80% in the sequential and alternating arms, respectively (P = .21). The sequential and alternating groups exhibited similar hematologic and nonhematologic toxicity. Both arms yielded similar complete response rate (42% and 40%), median PFS (32 months vs 34 months, P = .65), and 3-year overall survival (72% vs 74%, P = .63). The benefit of both schemes was remarkable in patients aged 65 to 75 years. In addition, achieving complete and immunophenotypic response was associated with better outcome. The present approach, based on VMP and Rd, is associated with high efficacy and acceptable toxicity profile with no differences between the sequential and alternating regimens. This trial was registered at www.clinicaltrials.gov as #NCT00443235.
Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (CAUSA/IBSAL), Salamanca, Spain;
María-Victoria
MV
Mateos
Hospital Universitario 12 de Octubre, Instituto de investigación 12 de Octubre, Madrid, Spain;
Joaquín
J
Martínez-López
Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain;
Miguel-Teodoro
MT
Hernández
Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (CAUSA/IBSAL), Salamanca, Spain;
Enrique-M
EM
Ocio
Hospital Clinic i Provincial, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;
Laura
L
Rosiñol
Hospital Clínico San Carlos, Madrid, Spain;
Rafael
R
Martínez
Hospital Clínico de Valencia, Valencia, Spain;
Ana-Isabel
AI
Teruel
Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (CAUSA/IBSAL), Salamanca, Spain;
Norma C
NC
Gutiérrez
Hospital Universitario 12 de Octubre, Instituto de investigación 12 de Octubre, Madrid, Spain;
María-Luisa
ML
Martín Ramos
Institut Català d'Oncologia, Institut Josep Carreras, Hospital Germans Trials i Pujol, Badalona, Barcelona, Spain;
Albert
A
Oriol
Hospital Son Llatzer, Palma de Mallorca, Spain;
Joan
J
Bargay
Hospital de Donostia, San Sebastian, Spain;
Enrique
E
Bengoechea
Institut d'Oncologia Dr. Josep Trueta, Girona, Spain;
Yolanda
Y
González
Hospital de Madrid Sanchinarro, Universidad Centro de Estudios Universitarios San Pablo, Madrid, Spain;
Jaime
J
Pérez de Oteyza
Hospital Vall d'Hebron, Barcelona, Spain;
Mercedes
M
Gironella
Hospital General Universitario Gregorio Marañón, Instituto de Investigacion Sanitaria Gregorio Marañón (IiSGM), Madrid, Spain;
Cristina
C
Encinas
Hospital General Virgen del Rocío, Sevilla, Spain;
Jesús
J
Martín
Hospital San Pedro de Alcántara, Cáceres, Spain; and.
Carmen
C
Cabrera
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
Bruno
B
Paiva
Hospital Universitario 12 de Octubre, Instituto de investigación 12 de Octubre, Madrid, Spain;
María-Teresa
MT
Cedena
Complejo Asistencial Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (CAUSA/IBSAL), Salamanca, Spain;
Noemí
N
Puig
Hospital Clinic i Provincial, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain;
Joan
J
Bladé
Hospital Universitario 12 de Octubre, Instituto de investigación 12 de Octubre, Madrid, Spain;
Juan-José
JJ
Lahuerta
Clínica Universidad de Navarra, Centro de Investigación Médica Aplicada (CIMA), Instituto de Investigación Sanitaria de Navarra (IDISNA), Pamplona, Spain.
Jesús
J
San-Miguel
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000069286:Bortezomib / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D003907:Dexamethasone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D000077269:Lenalidomide; D008297:Male; D008558:Melphalan / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D013792:Thalidomide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D000077269:Lenalidomide; D008558:Melphalan; D011241:Prednisone