Oral melphalan and prednisone chemotherapy plus thalidomide compared with melphalan and prednisone alone in elderly patients with multiple myeloma: randomised controlled trial.
BACKGROUND
Since 1960, oral melphalan and prednisone (MP) has been regarded as the standard of care in elderly multiple myeloma patients. This multicentre randomised trial compared oral MP plus thalidomide (MPT) with MP alone in patients aged 60-85 years.


METHODS
Patients with newly diagnosed multiple myeloma were randomly assigned to receive oral MP for six 4-week cycles plus thalidomide (n=129; 100 mg per day continuously until any sign of relapse or progressive disease) or MP alone (n=126). Analysis was intention-to-treat. This study is registered at , number NCT00232934.


RESULTS
Patients treated with thalidomide had higher response rates and longer event-free survival (primary endpoints) than patients who were not. Combined complete or partial response rates were 76.0% for MPT and 47.6% for MP alone (absolute difference 28.3%, 95% CI 16.5-39.1), and the near-complete or complete response rates were 27.9% and 7.2%, respectively. 2-year event-free survival rates were 54% for MPT and 27% for MP (hazard ratio [HR] for MPT 0.51, 95% CI 0.35-0.75, p=0.0006). 3-year survival rates were 80% for MPT and 64% for MP (HR for MPT 0.68, 95% CI 0.38-1.22, p=0.19). Rates of grade 3 or 4 adverse events were 48% in MPT patients and 25% in MP patients (p=0.0002). Introduction of enoxaparin prophylaxis reduced rate of thromboembolism from 20% to 3% (p=0.005).


CONCLUSIONS
Oral MPT is an effective first-line treatment for elderly patients with multiple myeloma. Anticoagulant prophylaxis reduces frequency of thrombosis. Longer follow-up is needed to assess effect on overall survival.
Palumbo
Antonio
A
Divisione di Ematologia dell'Università di Torino, Azienda Ospedaliera S Giovanni Battista, 10126 Torino, Italy. appalumbo@yahoo.com
Bringhen
Sara
S
Caravita
Tommaso
T
Merla
Emanuela
E
Capparella
Vincenzo
V
Callea
Vincenzo
V
Cangialosi
Clotilde
C
Grasso
Mariella
M
Rossini
Fausto
F
Galli
Monica
M
Catalano
Lucio
L
Zamagni
Elena
E
Petrucci
Maria Teresa
MT
De Stefano
Valerio
V
Ceccarelli
Manuela
M
Ambrosini
Maria Teresa
MT
Avonto
Ilaria
I
Falco
Patrizia
P
Ciccone
Giovannino
G
Liberati
Anna Marina
AM
Musto
Pellegrino
P
Boccadoro
Mario
M
D000368:Aged; D000369:Aged, 80 and over; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000401:mortality; D011241:Prednisone / Q000008:administration & dosage; D013792:Thalidomide / Q000008:administration & dosage
D018906:Antineoplastic Agents, Alkylating; D018931:Antineoplastic Agents, Hormonal; D013792:Thalidomide; D008558:Melphalan; D011241:Prednisone