ASH Clinical News ACN_4.4_SUPP_Digital Version | Page 29

and dexamethasone alone.
“The safety is consistent with previous findings, and no new safety
signals were observed for carfilzomib, lenalidomide, and dexameth-
asone after extended follow-up,” Dr. Stewart said. “This combination
should be considered a standard of care in relapsed/refractory MM.”
The study is limited by its open-label design, which may have
introduced bias.
The authors report financial relationships with Celgene and
Amgen.
SCENES FROM THE 2017 ASH ANNUAL MEETING
REFERENCE
Stewart AK, Siegel D, Ludwig H, et al. Overall survival (OS) of patients with
relapsed/refractory multiple myeloma (RRMM) treated with carfilzomib,
lenalidomide, and dexamethasone (KRd) versus lenalidomide and dexamethasone
(Rd): final analysis from the randomized phase 3 Aspire trial. Abstract 743.
Presented at the 2017 American Society of Hematology Annual Meeting, December
11, 2017; Atlanta, GA.
Final Analysis of IFM2009 Trial Confirms Predictive Value
of Minimal Residual Disease in Myeloma
Because survival for patients with multiple myeloma (MM)
has significantly improved within the past decade, complete
response (CR) rates may no longer be a clinically meaningful
endpoint. According to a final analysis of the IFM2009
trial presented at the 2017 ASH Annual Meeting, minimal
residual disease (MRD) could be considered a surrogate
biomarker in clinical trials of anti-myeloma therapies.
“We used a very sensitive technique – immunoglobulin
next-generation sequencing – in a prospective trial to [measure]
MRD and to correlate with progression-free and overall survival
(OS),” said lead author Hervé Avet-Loiseau, MD, PhD, of
IUCT-Oncopole in Toulouse, France, during his presentation of
the results. He added that MRD monitoring should be “included
in all upcoming trials [and] could become the primary endpoint
of future trials.”
IFM2009 included 700 patients with MM who were random-
ized to receive induction therapy with RVD (lenalidomide, bor-
tezomib, dexamethasone) with or without high-dose melphalan.
All patients also received 12 months of lenalidomide as mainte-
nance therapy. MRD was assessed before and after maintenance
therapy using the clonoSEQ kit, which can detect disease at a
level of 1×10 -6 .
MRD was evaluated in 269 patients who achieved at least a
very good partial response (VGPR). If patients did not achieve
VGPR, they were considered MRD-positive, and MRD negativi-
ty was defined as <1×10 -6 .
Using this cutoff, at a median follow-up of 55 months (range
not provided), the median progression-free survival (PFS)
among patients who achieved MRD negativity was not met,
compared with 29 months for patients who remained MRD-
positive (ranges and p values not provided). OS was also longer
in patients who achieved MRD negativity.
“We found that sensitivity is very important,” Dr. Avet-
Loiseau and co-authors added. “Patients with an MRD level
below 10 -6 presenting a [significantly] better PFS than patients
not achieving this level.”
Also, patients who achieved MRD negativity had similar sur-
vival rates regardless of whether they underwent hematopoietic
cell transplantation.
MRD negativity also appeared to be a more powerful pre-
dictor of survival outcome than cytogenetics: Participants with
high-risk cytogenetics who achieved MRD negativity had better
outcomes than patients with standard-risk cytogenetics who did
not achieve MRD negativity. This suggests that “high-risk cyto-
genetics is a dynamic concept that should be reevaluated during
treatment,” the researchers wrote.
MRD should be considered a novel surrogate biomarker
for trial evaluation, the researchers concluded. These findings
demonstrate that “the best sensitivity is associated with the best
discrimination in PFS and OS, and 10 -6 should be [used as] the
optimal cutoff.”
Dr. Avet-Loiseau noted several questions that remain, in-
cluding the role of imaging techniques and the role of circulating
cell-free tumor DNA in these evaluations.
The authors report financial relationships with Celgene, Janssen,
Amgen, Takeda, and Bristol-Myers Squibb.
REFERENCE
Avet-Loiseau H, Lauwers-Cances V, Corre J, et al. Minimal residual disease in
multiple myeloma: final analysis of the IFM2009 trial. Abstract #435. Presented
at the 2017 American Society of Hematology Annual Meeting, December 10, 2017;
Atlanta, GA.
March 2018
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