Written in Blood
0.5). Following cessation of ibrutinib, the median OS was 2.9 months (95% CI 1.6-4.9
mechanism of ibrutinib resistance.
months), compared with 0.8 months among those not receiving subsequent treatment.
To determine the outcomes of patients who experience ibrutinib failure, Dr. Mar“Although the response rate and side-effect profile of ibrutinib are unprecedented in
tin and co-authors conducted a large, international, retrospective, cohort study of all
patients with MCL who experienced disease progression while receiving ibrutinib across MCL, long-term remissions remain elusive, and the outcomes of patients who experience ibrutinib appears to be poor,” the researchers wrote. “Poor clini cal outcomes were
15 sites in the United States, United Kingdom, Germany, and Poland.
noted in the majority of patients with primary or secondary ibrutinib resistance.”
The authors analyzed medical records for clinical characteristics, pathologic and ra“Caution should be used when interpreting the average survival of patients in this
diologic data, and therapies used both before and after ibrutinib in 114 patients. Patients
were treated with a median of three prior therapies (range = 0-10 therapies). The average study,” the authors wrote, adding that, “despite the large sample size, there was limited
statistical power to evaluate all possible predictors of survival such as pre-ibrutinib
time between the last dose of prior therapy and initiation of ibrutinib was two months
therapies.”
(range = 0-59 months). At the start of ibrutinib treatment, 23 percent of patients had a
Given the poor outcomes with ibrutinib and post-ibrutinib treatment in these previlow MCL International Prognostic Index (MIPI) score, 31 percent had an intermediate
MIPI score, and 46 percent had a
high MIPI score.
The median duration of ibrutinib
use was 4.7 months (range = 7.4-12.1
months; 95% CI 3.8-5.7). Among
Only with FEIBA prophylaxis
those who responded to treatment,
the median duration was 8.6 months
(95% CI 7.4-12.1). The investigator-assessed best response rate to
ibrutinib was 55 percent, with 43
percent of patients achieving a partial
response and 12 percent achieving a
A clinical study showed*
complete response.
median Annual Bleed Rate (ABR)
The median OS from diagnowith on-demand treatment1,2
sis was 54 months (95% CI 43-70
629 bleeding episodes occurred
months). At the time of analysis,
during on-demand treatment1,2
only 29 patients were still alive; 85
had died. The causes of death were
lymphoma (79), treatment-related
toxicity (3), unrelated (2), and not
reported (1).
“The group of patients included in
median ABR with prophylaxis
the study appeared to be fairly high
treatment1,2 196 bleeding
risk before starting ibrutinib, and not
episodes occurred during
1
surprisingly, patients that were higher
prophylaxis treatment1,2
risk tended to do worse,” Dr. Martin
told ASH Clinical News. “Many of
these patients had also likely already
exhausted most standard therapies
before receiving ibrutinib.”
The presence of a BTK mutation
did not appear to act as a mechanism
of ibrutinib resistance, as seen from
the results of a BTK status assessment
*PROOF study: Phase 3, prospective, randomized, open-label
at relapse in 10 patients. “We found a
study in 17 patients who received FEIBA prophylaxis (85 ± 15
U/kg every other day) and 19 patients who received FEIBA
C481S mutation in two patients who
on-demand (dosages determined by treating physicians).1
received ibrutinib for 12.1 months
and 12.6 months,” Dr. Martin and
colleagues wrote. The other eight
patients with wild-type post-ibrutinib
BTK, however, received ibrutinib for
a median of 3.3 months, and only
FEIBA is an Anti-Inhibitor Coagulant Complex indicated for use in hemophilia A and B patients with inhibitors for:
one of these patients experienced a
• Control and prevention of bleeding episodes
durable response of more than one
• Perioperative management
year. “These numbers are small but
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes.
consistent with the hypothesis that
FEIBA is not indicated for the treatment of bleeding episodes resulting from coagulation factor deficiencies in the absence of inhibitors to
BTK mutation as a mechanism of
coagulation factor VIII or coagulation factor IX.
ibrutinib resistance in MCL is not
common and that other mechanisms
are likely more relevant.”
After stopping ibrutinib treatment, 73 patients (70%) received
WARNING: THROMBOEMBOLIC EVENTS
subsequent treatment (including
• Thromboembolic events have been reported during post-marketing surveillance following infusion of FEIBA, particularly
rituximab, lenalidomide, cytarabine,
following the administration of high doses and/or in patients with thrombotic risk factors.
bendamustine, bortezomib, anthra•
Monitor
patients receiving FEIBA for signs and symptoms of thromboembolic events.
cycline, and PI3K inhibitors). The
The
use
of
FEIBA
is contraindicated in patients with:
median time between the end of
• Known anaphylactic or severe hypersensitivity reactions to FEIBA or any of its components, including factors of the kinin generating system
ibrutinib treatment and the start of a
• Disseminated intravascular coagulation (DIC)
subsequent treatment was 0.3 months
(range = 0-21.7 months; 95% CI 0.2• Acute thrombosis or embolism (including myocardial infarction)
Help stop his bleed before it starts
72%
REDUCTION
IN MEDIAN
ANNUAL
BLEED RATE
28.7
7.9
Indications for FEIBA [Anti-Inhibitor Coagulant Complex]
Detailed Important Risk Information for FEIBA [Anti-Inhibitor
Coagulant Complex]
Thromboembolic events (including venous thrombosis, pulmonary embolism, myocardialinfarction, and stroke) can occur with FEIBA,
particularly following the administration of highdoses (above 200 units per kg per day) and/or in patients with thrombotic risk factors.
34
ASH Clinical News