Lenalidomide plus dexamethasone versus observation in patients with high-risk smouldering multiple myeloma (QuiRedex): long-term follow-up of a randomised, controlled, phase 3 trial
Por:
Mateos MV, Hernández MT, Giraldo P, de la Rubia J, de Arriba F, Corral LL, Rosiñol L, Paiva B, Palomera L, Bargay J, Oriol A, Prosper F, López J, Arguiñano JM, Quintana N, García JL, Bladé J, Lahuerta JJ and Miguel JF
Publicada:
1 ago 2016
Categoría:
Oncology
Resumen:
Background The standard of care for smouldering multiple myeloma is
observation. We did the QuiRedex study to compare early treatment with
lenalidomide plus dexamethasone with observation in patients with
high-risk smouldering multiple myeloma. Here we report the long-term
follow-up results of the trial.
Methods We did this open-label, randomised, controlled phase 3 study at
19 centres in Spain and three centres in Portugal. Patients aged 18
years or older with high-risk smouldering multiple myeloma were randomly
assigned (1: 1), via a computerised random number generator, to receive
either early treatment with lenalidomide plus dexamethasone or
observation, with dynamic balancing to maintain treatment balance within
the two groups. Randomisation was stratified by time from diagnosis of
smouldering multiple myeloma to study enrolment (<= 6 months vs >6
months). Patients in the treatment group received nine 4-week induction
cycles (lenalidomide 25 mg per day on days 1-21, plus dexamethasone 20
mg per day on days-1-4 and days 12-15), followed by maintenance therapy
(lenalidomide 10 mg per day on days 1-21 of each 28-day cycle) up to 2
years. Group allocation was not masked from study investigators or
patients. The primary endpoint was time from randomisation to
progression to symptomatic myeloma. The primary analysis was based on
the per-protocol population, restricted to patients who fulfilled the
protocol in terms of eligibility. Safety assessments were based on the
intention-to-treat population. This trial is registered with
ClinicalTrials.gov, number NCT00480363.
Findings Between Nov 8, 2007, and June 9, 2010, 125 patients were
enrolled and underwent randomisation. 119 patients comprised the
per-protocol population and were randomly assigned to receive either
lenalidomide plus dexamethasone (n=57) or observation (n=62). The cutoff
date for this update was June 30, 2015. Median follow-up for surviving
patients was 75 months (IQR 67-85). Lenalidomide plus dexamethasone
continued to provide a benefit on time to progression compared with
observation (median time to progression not reached [95% CI 47
months-not reached] vs 23 months [16-31]; hazard ratio [HR] 0.24 [95% CI
0.14-0.41]; p<0.0001). Progression to multiple myeloma occurred in 53
(86%) of 62 patients in the observation group compared with 22 (39%) of
57 patients in the treatment group. At data cutoff, ten (18%) patients
had died in the treatment group and 22 (36%) patients had died in the
observation group; median overall survival from the time of study entry
had not been reached in either group (95% CI 65 months-not reached vs 53
months-not reached; HR 0.43 [95% CI 0.21-0.92], p=0.024). Survival in
patients who had received subsequent treatments at the time of
progression to active disease did not differ between groups (HR 1.34
[95% CI 0.54-3.30]; p=0.50). The most frequently reported grade 3
adverse events in patients given lenalidomide plus dexamethasone were
infection (four [6%]), asthenia (four [6%]), neutropenia (three [5%]),
and skin rash (two [3%]); these events all occurred during induction
therapy. No grade 4 adverse events occurred, but one (2%) patient in the
lenalidomide plus dexamethasone group died from a respiratory infection
during induction therapy The frequency of second primary malignancies
was higher in patients in the treatment group than in those in the
observation group (six [10%] of 62 patients vs one [2%] of 63 patients),
but the cumulative risk of development did not differ significantly
between the groups (p=0.070).
Interpretation This study is, to our knowledge, the first randomised
trial in which early treatment has been assessed in selected patients
with high-risk smouldering multiple myeloma. Positive results from
ongoing trials would support the use of early treatment for patients
with high-risk disease in the near future.
Filiaciones:
Mateos MV:
Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Instituto de Biología Molecular y Celular del Cáncer, Salamanca, Spain.
Hernández MT:
Hospital Universitario de Canarias, Tenerife, Spain
Giraldo P:
Hospital Miguel Servet, Zaragoza, Spain
:
Hospital Universitario La Fe, Valencia, Spain
de Arriba F:
Hospital Morales Messeguer, Murcia, Spain
Corral LL:
Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Instituto de Biología Molecular y Celular del Cáncer, Salamanca, Spain
Rosiñol L:
Hospital Clinic, IDIBAPS, Barcelona, Spain
Paiva B:
Clínica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain
Palomera L:
Hospital Lozano Blesa, Zaragoza, Spain
Bargay J:
Hospital Sont Llàtzer, Palma de Mallorca, Spain
Oriol A:
Hospital Germans Trias i Pujol, Badalona, Spain
Prosper F:
Clínica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain
López J:
Hospital Ramón y Cajal, Madrid, Spain
Arguiñano JM:
Complejo Hospitalario de Navarra, Pamplona, Spain
Quintana N:
Celgene, Madrid, Spain
García JL:
Celgene, Madrid, Spain
Bladé J:
Hospital Clinic, IDIBAPS, Barcelona, Spain
Lahuerta JJ:
Hospital 12 de Octubre, Madrid, Spain
Miguel JF:
Clínica Universidad de Navarra, CIMA, IDISNA, Pamplona, Spain
|