CLINICAL NEWS
For Lenalidomide-Refractory Myeloma, Pomalidomide Is a Safe, Effective Secondline Option
While it has become a standard to include
lenalidomide in the frontline treatment
of patients with multiple myeloma (MM),
most patients have disease that will become
refractory to lenalidomide-based regimens.
According to results from a phase I/II
trial published in Blood, secondline
treatment that includes pomalidomide
could lead to high response rates.
“[Pomalidomide, bortezomib,
and dexamethasone (PVD)] is an
appealing secondline option in many
patients given the well accepted
use of lenalidomide-containing
regimens in the frontline setting
and lenalidomide-maintenance
therapy after [hematopoietic cell
transplantation (HCT)],” wrote the
authors, led by Jonas Paludo, MD,
from the Mayo Clinic College of
Medicine in Rochester, Minnesota.
The combination also incorporated
a reduced dosing frequency of
bortezomib, for “a simpler, more
convenient, and potentially better-
tolerated schedule.”
The prospective, non-randomized,
open-label trial included patients with
MM that was refractory to lenalido-
mide. Patients were excluded if they
had an uncontrolled infection, another
active malignancy, deep vein thrombo-
sis, an Eastern Cooperative Oncology
Group performance status score of ≥3,
or grade >2 peripheral neuropathy.
The researchers enrolled 50 pa-
tients (median age = 65.5 years; range
= 45-83 years) between March 2012
and July 2014. Patients had received a
median of two prior regimens (range
= 1-5 regimens). Most (72%) had
undergone HCT and 58 percent had
received bortezomib previously.
The median time from diagnosis
to enrollment was 50 months (range =
1.5-142 months). Patients had standard
(n=29; 58%), intermediate (n=9; 18%),
and high-risk (n=12; 24%) disease, ac-
cording to the Mayo Clinic’s mSMART
guidelines, a tool for stratifying newly
diagnosed and relapsed patients.
In the phase I trial, nine patients
received pomalidomide and dexametha-
sone with either bortezomib 1.0 mg/m 2
(n=3) or 1.3 mg/m 2 (n=6) intravenously
on days one, eight, 15, and 22 of each
28-day cycle to determine the maxi-
mum tolerated dose (MTD; primary
endpoint of phase I). No dose-limiting
toxicities (DLTs) were reported at the
1.0 mg/m 2 dose, and one DLT (hospital-
ization for pancytopenia and infection)
was reported at the 1.3 mg/m 2 dose, so
the researchers selected 1.3 mg/m 2 as
the MTD for the phase II trial.
After a median follow-up of 42
months (range = 13-59 months),
the objective response rate (ORR;
primary endpoint of phase II) was
ASHClinicalNews.org
86 percent (95% CI 73-94), including:
• stringent complete response (CR):
12% (n=6)
• CR: 10% (n=5)
• very good partial response (PR):
28% (n=14)
• PR: 36% (n=18)
One patient experienced a molecular re-
sponse (2%) and six had stable disease (12%).
At the time of analysis (date not
reported), 40 patients had progressive
disease (80%) and 17 had died (34%).
The median progression-free survival
(PFS) was 13.7 months (95% CI 9.7-17.7),
and the median overall survival (OS) had
not been reached. PVD appeared to be ef-
fective even in high-risk disease with PFS of:
• 12.3 months in high-risk disease
(95% CI 5.2-24.6)
• 9 months in intermediate-risk disease
(95% CI 3.2-22.9)