NEWS
ASPEN: Comparing Zanubrutinib With Ibrutinib in Waldenström Macroglobulinemia
Treatment with the selective Bruton tyrosine
kinase (BTK) inhibitor zanubrutinib resulted in
a higher combined complete response (CR) and
very good partial response (VGPR) rate than
therapy with the first-generation BTK inhibitor
ibrutinib in patients with Waldenström macroglobulinemia
(WM), according to findings from
the phase III ASPEN trial. Trial
results were first reported at the
2019 American Society of Hematology
(ASH) Annual Meeting; the
updated data included an additional
5 months of follow-up.
Study author Constantine Tam,
MD, of the Peter MacCallum Cancer
Center in Melbourne, Australia, who
presented the findings of this trial
as part of the ASCO20 Virtual Scientific
Program, said, “Compared with
other therapies, zanubrutinib’s ability
to be selective against a panel of
target enzymes provides the opportunity
to inhibit BTK with reduced
side effects.”
ASPEN enrolled 201 patients
with WM and a MYD88 mutation
(MYD88 MUT WM) and 28 patients
with wild-type MYD88 WM
(MYD88WT WM). Patients with
MYD88MUT were randomized to
either twice-daily zanubrutinib 160
mg (n=102) or once-daily ibrutinib
420 mg (n=99). Randomization
was stratified by CXCR4 status
(CXCR4W HIM vs. CXCR4 WT vs. missing)
and number of prior lines of
therapy (0 vs. 1-3 vs. >3). The 28
patients with MYD88 WT WM were
not randomized but were treated
with twice-daily zanubrutinib 160
mg, since ibrutinib has little efficacy
in MYD88 WT WM. Treatments
were administered until disease
progressed or adverse effects (AEs)
became intolerable.
Efficacy was determined by the
proportion of patients who achieved
either a CR or VGPR during treatment,
which was the primary endpoint.
The trial also assessed the
incidence, duration, and severity of
treatment-emergent AEs.
In both the zanubrutinib and
ibrutinib groups, the median age
was 70 years (range = 38-90). A
higher proportion of patients in the
zanubrutinib group were >75 years
of age (33% vs. 22%). Most patients
within both the zanubrutinib and
ibrutinib treatment arms entered
the trial having received 1 to 3 prior
lines of therapy (74.5% vs. 74.7%,
respectively). A higher proportion
of patients in the zanubrutinib arm
(65.7%) had a hemoglobin level of
≤110 g/dL, compared with 53.5% of
patients in the ibrutinib group.
Treatment with zanubrutinib was associated
with fewer discontinuations than treatment
with ibrutinib (n=4 vs. n=9, respectively)
and fewer deaths were attributed to AEs (n=1 vs.
n=4). A lower proportion of zanubrutinib-treated
patients experienced an AE that led to dose
reductions (13.9% vs. 23.5%) or doses being
held (46.5% vs. 56.1%). In contrast, neutropenia
was more common with zanubrutinib compared
with ibrutinib (all-grade events, 25% vs. 12%,
respectively).
Atrial fibrillation or atrial flutter was significantly
higher for ibrutinib than zanubrutinib
NOW APPROVED
FOR A NEW INDICATION
TAZVERIK TM (tazemetostat) is indicated for the treatment of:
• Adult patients with relapsed or refractory follicular
lymphoma whose tumors are positive for an EZH2
mutation as detected by an FDA-approved test and
who have received at least 2 prior systemic therapies.
• Adult patients with relapsed or refractory follicular
lymphoma who have no satisfactory alternative
treatment options.
These indications are approved under accelerated
approval based on overall response rate and duration of
response. Continued approval for these indications may
be contingent upon verification and description of clinical
benefit in a confirmatory trial(s).
Learn more at TAZVERIK.com
ASHClinicalNews.org