H e m a t o lo g y E d u c a t io n - European Hematology Association

dence of peripheral neuropathy, gastrointestinal complications,
and herpes zoster infections was higher with
VMP. VMP is also considered as another standard of
care for elderly patients. In this regimen, the weekly
infusion of bortezomib significantly reduces the incidence
of PN. When comparing the VMP regimen with
the bortezomib, thalidomide, and prednisone (VTP) regimen,
there was no significant difference in ORR, but
VMP had less adverse events than VTP. 51 The thalidomide
plus VMP (VMPT) regimen did result in higher
VGPR and CR rates than the VMP regimen. 52 When
weekly infusions of bortezomib were used in the VMPT
schema, the incidence of grade 3–4 PN was reduced in
comparison with the standard biweekly infusion without
influencing the outcome. Maintenance with bortezomib
after VMP or VMPT as frontline treatment looks
promising.
MP-lenalidomide
The combination of melphalan-prednisone and
lenalidomide (MPR) at the maximum tolerated dose (0.18
mg/kg melphalan, 2 mg/kg prednisone and 10 mg
lenalidomide) achieved an ORR of 81%, 48% VGPR,
median time to progression of 28 months in a phase 1/2
study. 53 The most common grade 3/4 adverse events
were neutropenia and thrombocytopenia (52% and 24%,
respectively at the maximum tolerated dose), febrile neutropenia
(9%), vasculitis (9%), and thrombosis/embolism
(5%). More than 40% of patients required growth factor
support. These results were the basis of the prospective
phase 3 randomized trial comparing MPR versus MPR
followed by R maintenance versus MP. The primary endpoint
of the study is time-to-progression, and preliminary
results are in favor of the MPR-R arm. 54
Lenalidomide plus dexamethasone
Dexamethasone has also been combined with
lenalidomide (Revlimid ® ), (Rev-Dex) for de novo MM
patients. Elderly patients represented half the population
of the 34 cases enrolled in the phase 2 trial using
Rev-Dex. 55 Lenalidomide was given orally 25 mg daily
on days 1 to 21 of a 28-day cycle; high-dose dexamethasone
was given orally 40 mg daily on days 1 to 4, 9 to
Table 4. Novel agents as primary treatment in elderly patients.
London, United Kingdom, June 9-12, 2011
12, and 17 to 20 of each cycle. The overall objective
response rate was impressive, 91%, and 55% of
patients experienced grade 3 or higher non-hematologic
toxicity. Rev-Dex regimen is thus a highly active regimen,
but the high-dose dexamethasone combination
might be unnecessary, and responsible for detrimental
side-effects. To solve this issue, the ECOG group initiated
a prospective randomized trial (ECOG E4A03) comparing
lenalidomide plus high-dose dexamethasone (40
mg daily, days 1–4, 9–12, 17–20) (Rev/High-dose dex)
with lenalidomide plus low-dose dexamethasone (40
mg daily, days 1, 8, 15, 22) (Rev/low-dose dex). 56 Four
hundred and forty-five patients, median age 66 years
(up to 88 years), were treated, including 233 over the
age of 65 years. Results clearly indicated that Rev/highdose
dex was significantly more toxic as compared with
Rev/low-dose dex. Infection/pneumonia, fatigue,
hyperglycemia, deep vein thrombosis, and cardiac
ischemia were more frequent with the Rev/high-dose
dex schedule. Overall, non-hematologic toxicity of any
type grade greater than or equal to 3 was found in 52%
of patients receiving Rev/high-dose dex compared with
34% of patients receiving Rev/low-dose dex (p