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CLINICAL NEWS
Carfilzomib Versus Bortezomib: Comparing Proteasome Inhibitors
in Newly Diagnosed Myeloma
Carfilzomib plus melphalan and prednisone
(KMP) failed to improve survival outcomes for
patients with newly diagnosed multiple my-
eloma (MM) compared with bortezomib plus
melphalan and prednisone (VMP), according
to results from the phase III CLARION trial
published in Blood.
In this randomized, open-label,
international trial, Thierry Facon, MD,
from the Hôpital Claude Huriez in Lille,
France, enrolled adults with previously
untreated MM who were considered
ineligible for autologous hematopoietic
cell transplantation. Eligible patients
had measurable disease and an Eastern
Cooperative Oncology Group perfor-
mance score of 0 to 2.
A total of 955 patients were random-
ized 1:1 to receive either:
very good partial response or better, though a
similar proportion of patients in the KMP and
VMP groups achieved a complete response.
Also, the median duration of response was
similar between both groups: 25.2 months
(range = 21.3 months to not estimable) versus
22.8 months (range = 20.2-25.8 months; p
value not reported).
Rates of minimal residual disease (MRD)–
negativity, another secondary endpoint, were
again similar between the KMP and VMP
groups among the 327 evaluable patients
(15.7% and 15.5%, respectively). Achieving
MRD-negative disease was associated with
• KMP: carfilzomib 20 mg/m 2 admin-
istered as a 30-minute intravenous
infusion on days 1 and 2 of cycle 1 and
36 mg/m 2 thereafter (n=478)
• VMP: bortezomib 1.3 mg/m 2 on days
1, 4, 8, 11, 22, 25, 29, and 32 (n=477)
In addition, patients received melphalan
9 mg/m 2 and prednisone 60 mg/m 2 on
days one through four of each cycle with
both regimens.
Patients were treated for a maximum
of nine 42-day cycles or until disease
progression, unacceptable toxicity, with-
drawal of consent, or death. No crossover
between treatment arms was permitted.
The median age was 72 years in both
arms (range not provided), and the
authors noted that “there were no major
imbalances in terms of baseline char-
acteristics between the two treatment
groups.”
At a median follow-up of 22 months
(range not reported), the median
progression-free survival (PFS) was
comparable between the two treatment
groups: 22.3 months in the KMP group
versus 22.1 months in the VMP group
(hazard ratio [HR] = 0.906; 95% CI
0.746-1.101; p=0.16).
Median overall survival also was sim-
ilar and not reached in either group. In
the KMP and VMP groups, 107 patients
(22.4%) and 95 patients (19.9%) died
(HR=1.08; 95% CI 0.82-1.43; p=0.7).
However, in exploratory analyses,
the authors found that patients treated
with KMP appeared to have a longer
median time to progression than those
treated with VMP: 27.5 months (range
= 22.4 months to not estimable) versus
23.5 months (range = 21.0-27.7 months;
HR=0.841; 95% CI 0.679-1.041; p=0.05).
As seen in the TABLE on page 22,
response rates appeared to be higher in
the KMP group, with a higher rate of
Nuclear export
dysregulation is
stealing the cell’s
valuable anti-tumor
defenses 1
IT’S ONE OF THE GREATEST HEISTS IN
CANCER, AND NO ONE SAW IT COMING.
Dysregulated nuclear export has been secretly depleting
the nucleus of key anti-oncogenic proteins, allowing the
tumor to proliferate and survive. 1,2
Investigate the evidence at NuclearExport.com
References: 1. Gupta A, Saltarski JM, White MA, Scaglioni PP, Gerber DE. Therapeutic targeting of nuclear export inhibition
in lung cancer. J Thorac Oncol. 2017;12(9):1446-1450. 2. Sun Q, Chen X, Zhou Q, Burstein E, Yang S, Jia D. Inhibiting cancer
cell hallmark features through nuclear export inhibition. Signal Transduct Target Ther. 2016;1:16010.
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