CLINICAL NEWS
Ibrutinib Outperforms
Temsirolimus in Patients with
Relapsed/Refractory Mantle
Cell Lymphoma
Both ibrutinib and temsirolimus
are effective in patients with previously treated mantle cell lymphoma
(MCL). A recent randomized,
head-to-head, phase III study
showed that ibrutinib led to longer
progression-free survival (PFS) and
a higher objective response rate
(ORR) in these patients.
“MCL patients typically
achieve only short-term remissions with conventional therapies,
so the positive results seen with
ibrutinib in this phase III trial are
particularly striking,” said Simon
Rule, MD, from the Department
of Hematology at Derriford Hospital in Plymouth, United Kingdom, said during his presentation
at the 2015 ASH Annual Meeting
in Orlando, Florida, last month.
In the open-label RAY study, a
total of 280 patients (median age
= 68 years; range = 34-88 years)
were randomized 1:1 to receive:
• Ibrutinib: 560 mg once-daily
(n=139)
• Temsirolimus: 175 mg, ad-
ministered intravenously on
days 1, 8, and 15 of cycle one
followed by 75 mg on days 1,
8, and 15 during all subsequent cycles (n=141)
All patients had received one or
more prior therapies containing
rituximab, and all had experienced
disease progression after receiving a
median of two prior lines of therapy
(range = 1-9). Nearly two-thirds of
the patients in the study had intermediate- or high-risk disease.
PFS was the study’s primary
endpoint; secondary endpoints included ORR, overall survival (OS),
time to next treatment, time to
worsening of lymphoma symptoms,
and adverse events (AEs).
At the time of this reporting, the
median follow-up was 20 months.
Patients treated with ibrutinib had
a statistically significant reduction
in the risk of progression or death
compared with temsirolimus (median PFS=14.6 months vs. 6.2 months,
respectively; hazard ratio [HR] =
0.43; 95% CI 0.32-0.58; p<0.0001).
After two years of follow-up, the
PFS rate was 41 percent for ibrutinib
and 7 percent for temsirolimus.
ASHClinicalNews.org
The ORR was also significantly
higher for those receiving ibrutinib
compared to temsirolimus: 71.9 percent versus 40.4 percent (p<0.0001).
Median OS had not yet been reached
in the ibrutinib cohort, but was 21.3
months in the temsirolimus cohort
(HR=0.76; 95% CI 0.53-1.09).
Twenty-six patients (18.7%) in
the ibrutinib group and two patients
(1.4%) in the temsirolimus group
achieved a complete response (CR).
The median treatment duration was 14.4 months for ibrutinib
and three months for temsirolimus. Median time-to-next-treatment was 11.6 months for those
taking temsirolimus, but had not
been reached in the ibrutinib arm.
Dr. Rule noted that 32 patients
(23%) initially enrolled in the temsirolimus arm crossed over to receive
ibrutinib treatment. For patients
who received other anti-cancer therapies after disease progression with
either ibrutinib or temsirolimus,
ORR was about 20 percent in each
group; however, the rate of complete
response was higher among those
who received therapy after ibrutinib
than after temsirolimus.
The most common treatmentrelated AEs for ibrutinib were
diarrhea, fatigue, and cough, while
the most common AEs associated
with temsirolimus were thrombocytopenia, anemia, and diarrhea. The
incidence of treatment-related AEs
was consistently lower for patients
treated with ibrutinib compared with
temsirolimus, and fewer patients
discontinued treatment due to AEs
(12.9% vs. 29.5%). Disease progression was the most common cause of
death in the ibrutinib arm, while AEs
were the most common causes of
death in the temsirolimus arm.
“This study provides further
evidence that ibrutinib should be
considered the treatment of choice
for patients with previously treated
MCL,” Dr. Rule said. Future planned
trials will investigate the safety and
efficacy of ibrutinib in combination
with other treatments, as well as
earlier in the disease course. ●
REFERENCE
Rule S, Jurczak W, Jerkeman M, et al. Ibru