MEETING NEWS
Highlights from the 2019 ASH Annual Meeting
Zanubrutinib Active in Patients With Previously
Untreated Del17p CLL/SLL
Approximately 93% of patients with treatment-naïve chronic lym-
phocytic leukemia/small lymphocytic lymphoma (CLL/SLL) and
del17p responded to treatment with the next-generation Bruton
tyrosine kinase (BTK) inhibitor zanubrutinib, according to results
from the phase III SEQUOIA trial. Its safety profile also was con-
sistent with other BTK inhibitors, lead author Constantine S. Tam,
MBBS, MD, from the Peter MacCallum Cancer Centre and the
University of Melbourne in Australia, reported in his presentation
at the 2019 ASH Annual Meeting.
Dr. Tam shared results from arm C of the SEQUOIA trial,
a nonrandomized arm that included treatment-naïve pa-
tients with del17p CLL/SLL. “These patients are normally
not suitable candidates for chemotherapy, because we
know that [they] are resistant to chemotherapy,” Dr. Tam
told ASH Clinical News. Zanubrutinib, which was recently
approved by the FDA for the treatment of mantle cell lym-
phoma, was administered in twice-daily doses of 160 mg.
As of data cutoff (August 7, 2019), 109 patients (me-
dian age = 70 years; range = 42-86) were enrolled. Most
patients had CLL, while 10 (9.2%) had SLL. After a median
follow-up of 10 months (range = 5-18.1), 104 patients
remained on study treatment. Five patients discontinued
– 1 due to toxicity and 4 due to progressive disease.
Ninety-three patients (85.3%) experienced adverse
events (AEs). Common any-grade AEs (reported in ≥7.5% of
patients) included contusion (20.2%), rash (11.0%), upper
respiratory tract infection (10.1%), and nausea (10.1%).
Grade ≥3 AEs were reported in 40 patients (36.7%), in-
cluding 26 patients (23.9%) with a serious AE. The most
common grade ≥3 AEs included neutropenia (n=11; 10.1%),
pneumonia (n=4; 3.7%), and hypertension (n=3; 2.8%). One
patient died of grade 5 pneumonia 8 days after receiving
the last dose of zanubrutinib, the authors noted.
“Zanubrutinib had the same side-effect profile as nor-
mal BTK inhibitors, namely bleeding, infection, and atrial
fibrillation – albeit at a numerically lower rate than has
been reported with ibrutinib,” Dr. Tam said.
Response rates seen with zanubrutinib treatment were
high, with an overall response rate of 92.7%. This included:
• 2 complete responses (1.9%)
• 86 partial responses (78.9%)
• 13 partial responses with lymphocytosis (11.9%)
The responses appeared to be durable, the researchers
reported, with 95 patients experiencing remissions lasting
longer than 6 months.
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Focus on Lymphoid & Plasma Cell Malignancies
The next question, according to Dr. Tam, should be, “Is
this response rate better than what we would expect with
ibrutinib? It would be hazardous to draw comparisons be-
tween the two drugs right now, especially given that there
are two phase III studies comparing them head to head.”
The studies are set to report results in the next few years.
The present trial is limited by its relatively short follow-
up of 10 months, he noted. “We know from ibrutinib
experience that patients are going to do well in the short-
to medium-term, but obviously longer follow-up will be
required to confirm that these patients on zanubrutinib
who are responding well at 10 months will continue to
respond well at the 2-, 4-, and 5-year marks.”
Dr. Tam also noted that future research will focus on
the depth of responses. “These patients are going into
remission, but not into very deep remission, because, as a
class, BTK inhibitors control patients’ disease but don’t get
the patient to minimal residual disease–negative remis-
sions,” he said. Planned trials are looking at whether
adding venetoclax to zanubrutinib could improve respons-
es, based on research showing improvements when veneto-
clax was combined with ibrutinib.
The authors report relationships with BeiGene, which
sponsored the trial.
Reference
Tam CS, Robak T, Ghia P, et al. Efficacy and safety of zanubrutinib in patients with treatment-naive
chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) with del(17p): initial results
from arm C of the Sequoia (BGB-3111-304) trial. Abstract #499. Presented at the 2019 ASH Annual
Meeting, December 8, 2019; Orlando, FL.
Clarithromycin Improves
Responses but Fails to
Prolong Survival in Newly
Diagnosed Myeloma
Adding the antibiotic clarithromycin to lenalidomide plus dexa-
methasone improved the response rate in patients with multiple
myeloma (MM), compared with lenalidomide and dexamethasone
(Rd) alone. However, this higher efficacy did not translate to
improved survival, particularly among older patients, and the study
did not meet its primary objective, lead investigator Noemi Puig,
MD, PhD, from the Hospital Universitario de Salamanca in Spain,
reported at the 2019 ASH Annual Meeting.