Literature Scan
New and noteworthy research from the
medical literature landscape
Meta-Analysis of Maintenance Therapy in
Multiple Myeloma: Time to Rethink
Immunomodulatory-Based Maintenance Therapy?
Maintenance therapy with immunomodulatory drugs (IMiDs;
including thalidomide, lenalidomide, and pomalidomide) and the
proteasome inhibitors bortezomib
and carfilzomib has been shown to
increase event-free and progression-free survival (PFS) in patients
with multiple myeloma (MM), but
questions about their efficacy in
extending overall survival and the
safety of long-term use remain.
In a recent meta-analysis published in the Journal of the National Cancer Institute, Yucai Wang
and colleagues from the Department of Medicine at Rutgers New
Jersey Medical School in Newark,
New Jersey, examined randomized controlled trials (RCTs) that
studied the safety and efficacy of
thalidomide and lenalidomide as
maintenance therapy for patients
with MM, with the goal of establishing the best algorithms for MM
management.
Dr. Wang and co-authors
searched PubMed and abstract
databases for major hematology/
oncology meetings to identify 18
phase III RCTs, enrolling a total of
“IMiD-based
maintenance
therapy can
significantly
improve PFS
but not OS in
MM , regardless of AutoHCT status.”
—YUCAI WANG
34
ASH Clinical News
Effects of IMiD-Based Maintenance Therapy on Progression-Free
and Overall Survival
TABLE 1.
IMiD
Thalidomide/
lenalidomide
Thalidomide
Lenalidomide
Overall survival
Number
of trials
HR (95% CI)
p Value
HR (95% CI)
p Value
Combined
18
0.62 (0.57-0.67)
<0.001
0.93 (0.85-1.01)
0.082
With AutoHCT
9
0.61 (0.54-0.68)
<0.001
0.89 (0.73-1.07)
0.214
Without
AutoHCT
11
0.63 (0.55-0.71)
<0.001
0.95 (0.88-1.04)
0.273
Combined
12
0.66 (0.61-0.72)
<0.001
0.94 (0.85-1.05)
0.278
With AutoHCT
6
0.67 (0.61-0.74)
<0.001
0.90 (0.73-1.11)
0.343
Without
AutoHCT
7
0.66 (0.57-0.76)
<0.001
0.97 (0.85-1.11)
0.627
Combined
6
0.52 (0.44-0.62)
<0.001
0.87 (0.73-1.04)
0.135
With AutoHCT
3
0.49 (0.41-0.57)
<0.001
0.82 (0.48-1.41)
0.477
Without
AutoHCT
4
0.55 (0.43-0.72)
<0.001
0.95 (0.85-1.05)
0.308
7,730 patients. Among these trials,
IMiDs used in the maintenance
therapy regimen included thalidomide (12 trials) and lenalidomide (6
trials). IMiD-based maintenance
therapy was used after patients
received autologous hematopoietic
cell transplantation (AutoHCT)
in seven trials, and nine trials
evaluated the safety and efficacy of
maintenance therapy in the nontransplant setting. Two trials had
enrolled both transplant-eligible
and -ineligible patients.
Overall, IMiD-based maintenance therapy statistically
significantly improved the PFS
(hazard ratio [HR] = 0.62; 95%
TABLE 2.
Progression-free survival
AutoHCT
status
CI 0.57-0.67; p<0.001) in patients
with MM (TABLE 1). In subgroup
analyses, both thalidomide- and
lenalidomide-containing regimens
improved PFS. “[For thalidomide]
the PFS prolongation was observed
in all six studies (HR=0.56-0.73),
demonstrating an unequivocal
benefit of thalidomide maintenance therapy after AutoHCT in
delaying disease progression,” Dr.
Wang and colleagues noted.
This improvement was also
seen in both transplant and
non-transplant settings: HR=0.61
(95% CI 0.54-0.68; p<0.001) and
HR=0.63 (95% CI 0.55-0.71;
p<0.001), respectively.
Conversely, IMiD-based maintenance therapy was not associated with a statistically significant
improvement in overall survival
(OS), though there was a trend
for longer OS: HR=0.93 (95% CI
0.85-1.01; p=0.082). This was true
regardless of the type of IMiD used
or transplant eligibility:
• Thalidomide: HR=0.94 (95%
CI 0.85-1.05; p=0.278)
• Lenalidomide: HR=0.87 (95%
CI 0.73-1.04; p=0.135)
• Transplantation: HR=0.89
(95% CI 0.73-1.07; p=0.214)
Grade 3 or 4 Adverse Even ts
Adverse event
Number of trials
Events in IMiD arm
Risk ratio (95% CI)
p Value
Vascular events
10
123/1,958
2.52 (1.41-4.52)
0.002
Peripheral neuropathy
6
53/1,419
2.27 (1.35-3.84)
0.002
Neutropenia
9
484/1,894
2.73 (1.63-4.55)
<0.001
Thrombocytopenia
10
159/1,886
2.14 (1.34-3.40)
0.001
Anemia
10
149/1,955
1.43 (1.13-1.80)
0.003
Infection
9
297/1,654
1.64 (1.40-1.92)
<0.001
Fatigue
10
130/1,969
1.48 (1.08-2.03)
0.016
Constipation
7
36/1,502
1.82 (1.03-3.21)
0.039
Second primary
malignancies
7
93/1,593
1.33 (0.81-2.19)
0.257
January 2016