CLINICAL NEWS
On Location
Conference Coverage
PROGRESS IN TRANSPLANT
AND CELLULAR THERAPY
t the 2019 Transplantation & Cellular Therapy Meetings
of the American Society for Transplantation and Cellular
Therapy and the Center for International Blood & Marrow
Transplant Research, held February 20–24 in Houston,
investigators, clinicians, researchers, and health-care professionals
gathered to hear the latest updates in the field of hematopoietic
cell transplantation and cellular therapy.
Here, we continue our coverage of hematologic research
presented at the meeting, including gene therapy for transfusion-
dependent beta-thalassemia and “non-engineered” chimeric
antigen receptor T-cell therapies in lymphoma.
Post-Transplant Ixazomib Maintenance Prolongs Survival
in Newly Diagnosed Myeloma
For patients with newly diagnosed multiple
myeloma (MM) who relapse following auto-
logous hematopoietic cell transplantation
(AHCT), maintenance therapy with the oral
proteasome inhibitor (PI) ixazomib extended
survival, compared with placebo, according
to results from the TOURMALINE-MM3
trial that were presented at the 2019 Trans-
plantation & Cellular Therapy Meetings
of the American Society for Blood and
Marrow Transplantation and the Center for
International Blood & Marrow Transplant
Research.
Gareth Morgan, MD, from the My-
eloma Center at the University of Arkansas
for Medical Sciences, shared the results.
TOURMALINE-MM3 is a double-
blind, placebo-controlled, phase III study
that enrolled 656 adult patients with newly
diagnosed MM who had received standard
of care with a PI or immunomodulatory
drug prior to undergoing a single AHCT
with high-dose melphalan. Eligible patients
had experienced at least a partial response
to AHCT; those whose disease relapsed,
were unresponsive to frontline therapy, or
underwent a tandem AHCT or received
post-AHCT consolidation therapy were
excluded from the analysis.
Patients were stratified based on in-
duction protocol, pre-induction Interna-
tional Staging System (ISS) stage disease,
and response following AHCT, then
randomized 3:2 to receive either weekly
ASHClinicalNews.org
ixazomib (n=395) or matched placebo
(n=261). Ixazomib 3 mg was administered
on days 1, 8, and 15 of 28-day cycles for
two years or until disease progression or
unacceptable toxicity, up to 26 cycles. If
patients tolerated ixazomib 3 mg dur-
ing the first four cycles, the dose was
increased to 4 mg (n=317 in the ixazomib
group and n=222 in the placebo group).
Baseline characteristics were “standard
and consistent between placebo and treat-
ment groups,” Dr. Morgan said. The median
age in the ixazomib and placebo groups
were 58 years (range = 24-73 years) and 60
years (range = 37-73 years), respectfully.
Approximately one-third of patients
were minimal residual disease (MRD)–
negative at the time of randomization, and
nearly one-fifth of patients in each group had
high-risk cytogenetics. Patients began main-
tenance therapy at a median of 3.4 months
after transplant (range = 2.8-5.8 months).
As of April 16, 2018 (data cutoff), with
a median follow up of 31 months (inter-
quartile range [IQR] = 27.3-35.7 months),
the researchers observed a median
progression-free survival of 26.5 months
in the ixazomib group (range = 23.7-33.8
months) and 21.3 months (range = 18.0-
24.7 months) in the placebo group. This
translated to a 28-percent reduction in the
risk of disease progression or death for
patients who received ixazomib (hazard
ratio = 0.72; 95% CI 0.58-0.89; p=0.002).
Ixazomib maintenance also was as-
sociated with a deepening of responses
over time, the authors reported. Among
participants who had a very good partial
response at study entry, for example, 43
percent of ixazomib-treated patients im-
proved to a complete response (n=92/213),
compared with 32 percent in the placebo
arm (n=48/152; p=0.004).
Ixazomib treatment also was associ-
ated with a higher rate of conversion from
MRD-positive to MRD-negative status
(12% vs. 7%; p value not provided). “Out-
comes for MRD-negative patients were
better if they received maintenance with
ixazomib,” Dr. Morgan added, “which
suggests that merely achieving MRD-
negativity is not an endpoint in itself, and
you can improve the outcome of these
patients with prolonged therapy.”
In subgroup analyses, ixazomib was
“active across the board,” Dr. Morgan re-
ported, and the progression-free survival
benefit was evident across age groups, ISS
stage, cytogenetics, and renal function.
Discontinuation due to adverse
events (AEs) was low and similar across
both groups (7% for ixazomib and 5%
for placebo). However, the incidence of
grade ≥3 AEs appeared to be higher in the
ixazomib group (42% and 26%, respec-
tively), the most common of which were
infections (15% and 8%), gastrointestinal
disorders (6% and 1%), neutropenia (5%
and 3%), and thrombocytopenia (5% and
<1%; [p values for comparisons were not
reported]). Rates of secondary primary
malignancies were low, at 3 percent in both
arms. “AEs could be managed easily in the
clinic or with simple remedies and small
doses of steroids,” Dr. Morgan said.
He also noted that it is “too soon to
comment on the impact of ixazomib on
overall survival because there are not
enough follow-up data.”
In response to audience questions
following the presentation about where
ixazomib fits into the landscape of avail-
able maintenance therapy options, includ-
ing lenalidomide, Dr. Morgan cautioned
against a head-to-head comparison of
the agents. The choice between ixazomib
or lenalidomide depends on a patient’s
underlying disease characteristics, he
added. With this information, “we can
target [disease factors] to select the group
that would benefit most [from either
treatment].”
The authors report relationships with
Takeda and Millennium Pharmaceuticals,
which provided funding for the study.
REFERENCE
Morgan G, Dimopoulos M, Gay F, et al. Maintenance therapy with
the oral proteasome inhibitor (PI) ixazomib significantly prolongs
progression-free survival (PFS) following autologous stem cell
Transplantation (ASCT) in patients with newly diagnosed multiple
myeloma (NDMM): phase 3 Tourmaline-MM3 trial. Abstract #23.
Presented at the Transplantation & Cellular Therapy Meetings of ASBMT
and CIBMTR, February 20, 2019; Houston, TX.
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