MEETING NEWS
regardless of prior rituximab therapy, age, race, time since last
therapy or tumor burden. Median duration of response was longer
in the R2 group, as well (36.6 months vs. 21.7 months; HR=0.53;
95% CI 0.36-0.79; p=0.0015).
When asked about where R2 fits in the landscape of relapsed
FL, Dr. Leonard noted that, although there are several other
agents approved for recurrent FL, including single-agent ritux-
imab, “our data suggest that many patients could instead benefit
from the combination of R2.” However, the trial was not designed
to compare R2 with other regimens containing chemotherapy and
other agents, and these decisions “depend on individual patient
situations,” he added.
As a limitation of the study, Dr. Leonard noted that the trial pop-
ulation included a small number of patients with MZL, which may
limit the results’ generalizability to patients with MZL.
The authors report relationships with Celgene, the manufac-
turer of lenalidomide, which sponsored the trial.
REFERENCE
Leonard JP, Trněný M, Izutsu K, et al. AUGMENT: A phase III randomized study of
lenalidomide plus rituximab (R2) vs rituximab/placebo in patients with relapsed/
refractory indolent non-Hodgkin lymphoma. Abstract #445. Presented at the 2018 ASH
Annual Meeting, December 2, 2018; San Diego, CA.
Evaluating Ixazomib Regimens in Patients With Newly
Diagnosed Myeloma
Two studies presented at the 2018 ASH Annual Meeting explored
the use the oral proteasome inhibitor (PI) ixazomib in patients
with newly diagnosed multiple myeloma (MM). The first eval-
uated its efficacy as maintenance therapy for patients who
underwent post-autologous hematopoietic cell transplantation
(AHCT) and the second examined the feasibility and efficacy of an
ixazomib and daratumumab combination as induction therapy.
Ixazomib Maintenance
For the substantial portion of patients with MM who relapse
following AHCT, maintenance therapy with ixazomib could offer
a new treatment option to delay disease progression and extend
survival, according to results from the phase III, double-blind,
placebo-controlled, multicenter TOURMALINE-MM3 trial. 1 The
drug also was associated with deeper responses, while maintaining
a “favorable” safety profile, lead author Meletios A. Dimopoulos,
MD, from the National and Kapodistrian University of Athens
School of Medicine in Greece, said during his presentation.
While lenalidomide is a commonly used post-AHCT main-
tenance therapy, Dr. Dimopoulos noted that nearly one-third
of patients discontinue the drug due to toxicity. However, as an
oral PI, ixazomib has a less frequent administration and has been
shown to have manageable toxicity. “We think that these findings
show ixazomib to have a very good therapeutic value,” he added.
The TOURMALINE-MM3 trial enrolled 656 adult patients
with newly diagnosed MM who had received standard of
care with a PI or immunomodulatory drug (IMiD) 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 induction protocol, pre-
induction International Staging System (ISS) stage disease, and
response following AHCT, then randomized 3:2 to receive either
weekly ixazomib (n=395) or matched placebo (n=261). Ixazomib
18
Focus on Lymphoid Malignancies
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 during the first
four cycles, dose was increased to 4 mg (n=317 in the ixazomib
group and n=222 in the placebo group).
Participants’ median age was 58 years; “however, 15 percent of
patients were older than 65 years,” Dr. Dimopoulos noted. Nearly
one-fifth of patients in each group had high-risk cytogenetics.
Other baseline characteristics were similar between the treat-
ment groups: Most patients in each group (59%) had induction
therapy with a PI, while 11 percent in each group received an
IMiD and 30 percent in each group received both agents. Also, a
similar portion of patients in each group had achieved minimal
residual disease (MRD)–negative status (33% for both).
Most patients had experienced a very good partial response
(VGPR) following AHCT (45% in the ixazomib arm and 44%
in the placebo arm), and approximately one-third in each group
had a complete response (CR; 33% and 36%, respectively).
As of April 16, 2018 (data cutoff), the median duration of
treatment at 4 mg was 15.2 months (range = 0-22 months) in
the ixazomib arm and 16.6 months (range = 0-21 months) in the
placebo group.
Results from the primary endpoint analysis showed that
maintenance treatment with ixazomib prolonged median PFS,
compared with placebo (26.5 months vs. 21.3 months; hazard
ratio [HR] = 0.72; 95% CI 0.58-0.89; p=0.002).
The benefit in PFS was observed across subgroups, including:
• age (≥60 years vs. <75 years): HR=0.662 ISS stage III
disease: HR=0.0661
• cytogenetic risk: HR=0.625 for high risk and HR=0.648
for standard risk
Patients who received maintenance therapy with ixazomib also
had deeper responses, Dr. Dimopoulos noted. For example,