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absence of tumor plasma cells within 1
million bone marrow cells (i.e., a sensitivi-
ty of <10 -6 ). Patients who did not enter the
maintenance phase or did not achieve at
least a very good partial response [VGPR]
before entering the maintenance phase
were considered MRD positive.
Among the 509 patients included in the
intent-to-treat analysis (excluding those who
achieved at least a VGPR but who did not
have MRD information available), MRD-
negativity was achieved at least once dur-
ing maintenance in 127 patients (25%).
More patients in the transplant
arm achieved MRD negativity,
compared with the RVD-alone arm
(30% [n=73] vs. 20% [n=54]). This
translated to an adjusted odds ratio
for undetectable MRD of 1.65 (95%
CI 1.10-2.49; p=0.02) favoring the
intensive approach.
The median duration of follow-
up was 55, 50, and 38 months from
randomization, start of maintenance
therapy, and completion of mainte-
nance therapy, respectively (ranges
not provided). Overall, patients
who achieved MRD negativity had
significantly longer progression-free
survival (PFS) and overall survival,
compared with MRD-positive pa-
tients. Multivariate analyses adjusting
for treatment group and other strati-
fication factors also demonstrated
that MRD-negative status was the
strongest predictor for PFS ( TABLE 2 ).
“The MRD negativity rate did
not differ according to International
Staging System disease stage or cyto-
genetic risk profile (high vs. standard
risk),” the authors added, raising “the
possibility that achieving MRD nega-
tivity may overcome certain adverse
risk factors identified at diagnosis.”
Though these results support the
value of MRD status in this setting,
the researchers noted that many
patients were not evaluable for MRD
due to lack of diagnostic sample for
calibration, which may be a limita-
tion of this study. “The feasibility
of monitoring MRD over time is
limited by the invasive bone marrow
biopsy procedures, but serum-based
tests to facilitate this monitoring are
currently undergoing clinical evalua-
tion,” they wrote.
“NGS-determined MRD status
enables the identification of patient
subpopulations with highly different
prognoses,” the researchers conclud-
ed. “Consequently, in the future, this
endpoint could be used to inform
treatment decisions and provide
significant reassurance for myeloma
patients who achieve MRD negativ-
ity, regardless of their cytogenetic
risk profile or disease stage. It is also
clear that MRD opens the door to
evaluation of stratified therapy for
MM patients in future randomized
ASHClinicalNews.org
clinical trials.”
Corresponding authors report
financial relationships with
Adaptive Biotechnologies, the
manufacturer of the NGS platform
used in the trial. ●
REFERENCE
Perrot A, Lauwers-Cances V, Corre J, et al. Minimal residual
disease negativity using deep sequencing is a major
prognostic factor in multiple myeloma. Blood. 2018
September 24. [Epub ahead of print]
Progression-Free and Overall Survival Status According to
MRD Status
TABLE 2.
MRD-Negative MRD-Positive Hazard Ratio (95% CI) p Value
Start of maintenance therapy Not reached 29 months 0.22 (0.15-0.34) <0.001
Completion of maintenance
therapy Not reached 20 months 0.18 (0.12-0.29 <0.001
96% 86% 0.24 (0.11-0.54) 0.001
Median progression-free survival
Overall survival (3 years after com-
pletion of maintenance therapy)
MRD = minimal residual disease