IN THE LITERATURE
Lenalidomide Maintenance Extends Survival Over
Observation Alone in Newly Diagnosed Myeloma
New results from the large phase III Myeloma XI trial confirm that
maintenance therapy with lenalidomide improves progression-
free survival (PFS) over observation alone in patients with newly
diagnosed multiple myeloma (MM). However, in the intention-
to-treat analysis, lenalidomide maintenance was not associated
with improvement in overall survival (OS), according to findings
published in Lancet Oncology.
“These data are from the largest study ever conducted on
maintenance therapy in MM,” lead study investigator Graham
H. Jackson, MD, of Newcastle University in the U.K., told ASH
Clinical News. “The outcomes mirror previously published
meta-analysis data, confirming that, in a transplant-eligible
population of patients with MM, lenalidomide maintenance
prolongs the PFS by more than three years.”
The Myeloma XI trial enrolled 4,420 patients with newly
diagnosed symptomatic MM or non-secretory MM from more
than 100 centers. The study had three potential randomization
arms: induction treatment (allocation by transplantation-
eligibility status), intensification treatment (allocation by
response to induction therapy), and maintenance treatment.
A total of 1,971 patients were assigned to receive mainte-
nance therapy with either lenalidomide (10 mg on days 1-21 of
a 28-day cycle; n=1,137) or observation (n=834). All patients
had completed their assigned induction therapy per study pro-
tocol and had achieved at least a minimal response to protocol
treatment, including lenalidomide.
After a median follow-up of 31 months (interquartile range
= 18-50 months), median PFS (co-primary endpoint) from the
time to randomization was 39 months (range = 36-42 months)
in the lenalidomide group and 20 months in the observation-
alone group. This translated to a significantly lower risk of
disease progression or death in the lenalidomide group (hazard
ratio [HR] = 0.46; 95% CI 0.41-0.53; p<0.0001).
However, there was no significant difference in the other
co-primary endpoint of three-year OS: 78.6 percent in the
lenalidomide group and 75.8 percent in the observation group
(HR=0.87; 95% CI 0.73-1.05; p=0.15).
In subgroup analysis of transplant-eligible patients, how-
ever, lenalidomide was associated with improved OS (3-year
OS: 87.5%vs. 80.2%; HR=0.69 [95% CI 0.52-0.93]; p=0.014).
OS differences also were noted for patients with higher-risk
cytogenetic profiles:
Lenalidomide maintenance also was associated with an ac-
ceptable toxicity profile, the authors commented, although a
greater proportion of patients receiving lenalidomide experi-
enced serious adverse events (AEs) compared with patients on
observation (45% vs. 17%; p value not reported). In patients
who received lenalidomide during the study, the most common
grade 3 or 4 AEs included:
• neutropenia (33%)
• thrombocytopenia (7%)
• anemia (4%)
Infections represented the most common serious AEs in both
groups. More deaths occurred in the observation group (27%)
versus the lenalidomide group (21%), yet the deaths that oc-
curred in the lenalidomide group were not deemed attributable
to the maintenance therapy.
Taken together, “the manageable safety profile of this drug
and the encouraging results in subgroup analyses of patients
[including those eligible for transplant and with high-risk
cytogenetics], support further investigation of maintenance
lenalidomide in this setting,” the authors concluded.
“The main area of continued argument in the field of my-
eloma is whether patients with high-risk cytogenetics benefit
from lenalidomide maintenance,” Dr. Jackson said. “These data
suggest that patients with high-risk cytogenetics do indeed
benefit from lenalidomide maintenance.”
He also noted the differences in survival according to age.
“In older, transplant-ineligible patients, the data demonstrate
an impact on PFS and time to second disease progression, but
they do not demonstrate an OS advantage for patients who are
maintained on lenalidomide after induction therapy.”
The lack of powered subgroup analyses, missing cytogenetic
data for some patients, and the lack of prospectively collected
data on quality of life represent potential limitations of this
study, the researchers concluded.
The authors report relationships with Celgene, the manufac-
turer of lenalidomide.
REFERENCE
Jackson GH, Davies FE, Pawlyn C, et al. Lenalidomide maintenance versus observation
for patients with newly diagnosed multiple myeloma (Myeloma XI): a multicentre,
open-label, randomised, phase 3 trial. Lancet Oncol. 2019;20:57-73.
• standard risk: 86.4% vs. 81.3%
• high risk: 74.9% vs. 63.7%
• ultra-high risk: 62.9% vs. 43.5% (p values not
reported)
March 2019
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