NORTH CHICAGO, Ill.,
Dec. 7, 2019 /PRNewswire/
-- AbbVie (NYSE: ABBV), a research-based global
biopharmaceutical company, today announced results of a 7.5-year
pooled analysis showing earlier treatment with
IMBRUVICA® (ibrutinib) monotherapy compared to later
lines of therapy (LOT) extended progression-free survival (PFS) and
increased the likelihood of a complete response (CR) in patients
with relapsed/refractory (R/R) mantle cell lymphoma (MCL) –
demonstrating that some patients achieved a disappearance of any
signs of disease.
The updated pooled analysis includes three clinical trials:
Phase 2 SPARK, Phase 3 RAY and Phase 2 PCYC-1104. Patients
achieving a CR with IMBRUVICA had a strong response, with a median
duration of therapy longer than 5.5 years. These results were
presented today at the American Society of Hematology (ASH) Annual
Meeting.
"MCL is an aggressive B-cell malignancy in which most patients
have poor prognosis and are likely to relapse after their initial
line of therapy. For those treated with chemotherapy,
progression-free survival generally declines with each successive
line of treatment," said Simon Rule,
M.D., Professor in Haematology, Peninsula Medical School,
University of Plymouth, United
Kingdom. "These extended follow-up results from the pooled
analysis of ibrutinib compared to prior regimens are very
encouraging for patients with relapsed or refractory MCL – as they
showed treatment with ibrutinib at first relapse versus later lines
of therapy resulted in a median progression-free survival of longer
than two years."
"Building on the legacy of IMBRUVICA, these latest pooled data
presented at ASH, which represent the longest follow-up to-date in
mantle cell lymphoma, add to the unprecedented body of evidence
supporting the use of IMBRUVICA monotherapy to treat this rare and
aggressive form of non-Hodgkin's lymphoma," said Danelle James, M.D., M.A.S., IMBRUVICA Clinical
Development Lead, Pharmacyclics LLC, an AbbVie company. "We
continue to be pleased by the proven efficacy and safety profile of
this pioneering BTK inhibitor, which has shown to delay disease
progression and improve durable responses when used at first
relapse."
IMBRUVICA is a once-daily, first-in-class Bruton's tyrosine
kinase (BTK) inhibitor that is administered orally, and is jointly
developed and commercialized by Pharmacyclics LLC, an AbbVie
company, and Janssen Biotech, Inc.
Abstract #1538: Long-term outcomes with IMBRUVICA versus the
prior regimen: a pooled analysis in relapsed/refractory MCL with up
to 7.5 years of extended follow-up
Poster Presentation: Saturday,
December 7 at 5:30 p.m.
EST
The pooled analysis evaluated 370 patients with R/R MCL (median
2 [range 1-9] prior LOTs) enrolled in the SPARK (MCL2001;
NCT01599949), RAY (MCL3001; NCT01646021), and PCYC-1104
(NCT01236391) studies who received IMBRUVICA 560 mg orally once
daily. For the regimen prior to IMBRUVICA, time to next treatment
(TTNT) was used as a surrogate for PFS. Progression of disease
(POD) on frontline treatment was categorized as early (TTNT less
than 24 months) or late (TTNT of 24 months or longer). The median
follow-up and exposure for IMBRUVICA-treated patients were 41
months (0.2 – 92.4) and 11.1 months (0.03 – 92.4), respectively.
Treatment duration was three years or more in 22.4 percent of
patients.
Results showed overall median PFS on IMBRUVICA was 12.5 months
(9.8 – 16.6) compared to median TTNT on the prior regimen of 10.9
months (9.1-12.6). PFS for patients who received IMBRUVICA was
longer than TTNT on the prior regimen for 50 percent of patients;
for 27 percent of patients, PFS was longer than TTNT on the prior
regimen by 12 months or more. At five years, PFS rate was 19
percent and overall survival (OS) rate was 41 percent. In patients
with one prior LOT, median PFS was 25.4 months (17.5 – 51.8) and OS
was 61.6 months (36.0 – not estimable [NE]). In patients with a CR,
median PFS was 67.7 months (51.7 – NE) and OS was not reached
(NE-NE).
Additionally, of the 99 patients who received IMBRUVICA in
second-line, 43 percent had early frontline POD and 57 percent of
them had late frontline POD. In patients with early frontline POD,
median PFS with IMBRUVICA (13.8 months) was similar to median
frontline TTNT (14.0 months); median duration of response (DOR) and
OS on IMBRUVICA were 22.1 and 23.5 months, respectively. In
patients with late frontline POD, median PFS with IMBRUVICA (57.5
months) was longer than median frontline TTNT (42.2 months); median
DOR and OS on IMBRUVICA were not reached.
With up to 92 months of follow-up, 81.6 percent of patients had
Grade 3 or higher treatment-emergent adverse events (TEAEs) and
64.9 percent had serious adverse events (SAEs). The most common
Grade 3 or higher TEAEs were neutropenia (17 percent), pneumonia
(13.5 percent) and thrombocytopenia (12.4 percent). The most common
SAEs were pneumonia (13.2 percent), atrial fibrillation (5.7
percent), and dyspnea (4.3 percent).
About IMBRUVICA
IMBRUVICA (ibrutinib) is an oral, once-daily medicine that
works differently than chemotherapy as it blocks a protein called
Bruton's tyrosine kinase (BTK). The BTK protein sends important
signals that tell B cells to mature and produce antibodies. BTK
signaling is needed by specific cancer cells to multiply and
spread. By blocking BTK, IMBRUVICA may help move abnormal B cells
out of their nourishing environments in the lymph nodes, bone
marrow, and other organs.
Since its launch in 2013, IMBRUVICA has received 10 FDA
approvals across six disease areas:
chronic lymphocytic leukemia (CLL) with or without 17p deletion
(del17p); small lymphocytic lymphoma (SLL) with or without del17p;
Waldenström's macroglobulinemia (WM); previously-treated patients
with mantle cell lymphoma (MCL)*; previously-treated patients with
marginal zone lymphoma (MZL) who require systemic therapy and have
received at least one prior anti-CD20-based therapy* – and
previously-treated patients with chronic graft-versus-host disease
(cGVHD) after failure of one or more lines of systemic
therapy.
IMBRUVICA is now approved in 95 countries and has been
used to treat more than 170,000 patients worldwide across its
approved indications. IMBRUVICA is the only FDA-approved medicine
in WM and cGVHD. IMBRUVICA has been granted four Breakthrough
Therapy Designations from the U.S. FDA. This designation is
intended to expedite the development and review of a potential new
drug for serious or life-threatening diseases. IMBRUVICA was one of
the first medicines to receive FDA approval via the Breakthrough
Therapy Designation pathway.
The NCCN Clinical Practice Guidelines in Oncology (NCCN
Guidelines®) for CLL recommends ibrutinib
(IMBRUVICA®) as a preferred regimen for the initial
treatment of CLL/SLL and it is the only Category 1 single-agent
regimen for treatment-naïve patients without deletion
17p.
IMBRUVICA is being studied alone and in combination with
other treatments in several blood and solid tumor cancers and other
serious illnesses. IMBRUVICA is the most comprehensively studied
BTK inhibitor, with more than 150 ongoing clinical trials. There
are approximately 30 ongoing company-sponsored trials, 14 of which
are in Phase 3, and more than 100 investigator-sponsored trials and
external collaborations that are active around the world. For more
information, visit www.IMBRUVICA.com.
*Accelerated approval was granted for the MCL and MZL
indications based on overall response rate. Continued approval for
MCL and MZL may be contingent upon verification and description of
clinical benefit in confirmatory trials.
IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS
Hemorrhage: Fatal bleeding events have occurred in
patients treated with IMBRUVICA®. Major hemorrhage
(≥ Grade 3, serious, or any central nervous system events;
e.g., intracranial hemorrhage [including subdural hematoma],
gastrointestinal bleeding, hematuria, and post procedural
hemorrhage) have occurred in 4% of patients, with fatalities
occurring in 0.4% of 2,838 patients exposed to
IMBRUVICA® in 27 clinical trials. Bleeding events
of any grade, including bruising and petechiae, occurred in 39% of
patients treated with IMBRUVICA®.
The mechanism for the bleeding events is not well
understood.
Use of either anticoagulant or antiplatelet agents concomitantly
with IMBRUVICA® increases the risk of major hemorrhage.
In IMBRUVICA® clinical trials, 3.1% of patients taking
IMBRUVICA® without antiplatelet or anticoagulant therapy
experienced major hemorrhage. The addition of antiplatelet
therapy with or without anticoagulant therapy increased this
percentage to 4.4%, and the addition of anticoagulant therapy with
or without antiplatelet therapy increased this percentage to
6.1%. Consider the risks and benefits of anticoagulant or
antiplatelet therapy when co-administered with
IMBRUVICA®. Monitor for signs and symptoms of
bleeding.
Consider the benefit-risk of withholding IMBRUVICA®
for at least 3 to 7 days pre- and post-surgery depending upon the
type of surgery and the risk of bleeding.
Infections: Fatal and non-fatal infections
(including bacterial, viral, or fungal) have occurred with
IMBRUVICA® therapy. Grade 3 or greater infections
occurred in 24% of 1,124 patients exposed to IMBRUVICA®
in clinical trials. Cases of progressive multifocal
leukoencephalopathy (PML) and Pneumocystis jirovecii
pneumonia (PJP) have occurred in patients treated with
IMBRUVICA®. Consider prophylaxis according to standard
of care in patients who are at increased risk for opportunistic
infections.
Monitor and evaluate patients for fever and infections and treat
appropriately.
Cytopenias: Treatment-emergent Grade 3 or 4
cytopenias including neutropenia (23%), thrombocytopenia (8%), and
anemia (3%) based on laboratory measurements occurred in patients
with B‑cell malignancies treated with single agent
IMBRUVICA®.
Monitor complete blood counts monthly.
Cardiac Arrhythmias: Fatal and serious cardiac
arrhythmias have occurred with IMBRUVICA® therapy.
Grade 3 or greater ventricular tachyarrhythmias occurred in 0.2% of
patients, and Grade 3 or greater atrial fibrillation and atrial
flutter occurred in 4% of 1,124 patients exposed to
IMBRUVICA® in clinical trials. These events have
occurred particularly in patients with cardiac risk factors,
hypertension, acute infections, and a previous history of cardiac
arrhythmias.
Periodically monitor patients clinically for cardiac
arrhythmias. Obtain an ECG for patients who develop arrhythmic
symptoms (e.g., palpitations, lightheadedness, syncope, chest pain)
or new onset dyspnea. Manage cardiac arrhythmias
appropriately, and if it persists, consider the risks and benefits
of IMBRUVICA® treatment and follow dose modification
guidelines.
Hypertension: Hypertension of any grade occurred in
12% of 1,124 patients treated with IMBRUVICA® in
clinical trials. Grade 3 or greater hypertension occurred in 5% of
patients with a median time to onset of 5.9 months (range, 0.03 to
24 months).
Monitor blood pressure in patients treated with
IMBRUVICA® and initiate or adjust anti-hypertensive
medication throughout treatment with IMBRUVICA® as
appropriate.
Second Primary Malignancies: Other malignancies
(10%) including non-skin carcinomas (4%) have occurred in 1,124
patients treated with IMBRUVICA® in clinical trials. The
most frequent second primary malignancy was non-melanoma skin
cancer (6%).
Tumor Lysis Syndrome: Tumor lysis syndrome has been
infrequently reported with IMBRUVICA® therapy. Assess
the baseline risk (e.g., high tumor burden) and take appropriate
precautions.
Monitor patients closely and treat as appropriate.
Embryo-Fetal Toxicity: Based on findings in animals,
IMBRUVICA® can cause fetal harm when administered to a
pregnant woman. Advise women to avoid becoming pregnant while
taking IMBRUVICA® and for 1 month after cessation of
therapy. If this drug is used during pregnancy or if the patient
becomes pregnant while taking this drug, the patient should be
apprised of the potential hazard to a fetus. Advise men to avoid
fathering a child during the same time period.
ADVERSE REACTIONS
B-cell malignancies: The most common adverse
reactions (≥20%) in patients with B-cell malignancies (MCL,
CLL/SLL, WM and MZL) were thrombocytopenia (58%)*, diarrhea (41%),
anemia (38%)*, neutropenia (35%)*, musculoskeletal pain (32%), rash
(32%), bruising (31%), nausea (26%), fatigue (26%), hemorrhage
(24%), and pyrexia (20%).
The most common Grade 3 or 4 adverse reactions (≥5%) in patients
with B-cell malignancies (MCL, CLL/SLL, WM and MZL) were
neutropenia (18%)*, thrombocytopenia (16%)*, and pneumonia
(14%).
Approximately 7% (CLL/SLL), 14% (MCL), 14% (WM)
and 10% (MZL) of patients had a
dose reduction due to adverse reactions.
Approximately 4-10% (CLL/SLL), 9% (MCL), and
7% (WM [5%] and MZL [13%]) of patients
discontinued due to adverse reactions.
cGVHD: The most common adverse reactions (≥20%) in patients with cGVHD were fatigue (57%), bruising (40%), diarrhea (36%), thrombocytopenia (33%)*, muscle spasms (29%),
stomatitis (29%), nausea (26%),
hemorrhage (26%), anemia (24%)*, and pneumonia
(21%).
The most common Grade 3 or higher adverse reactions (≥5%) reported in patients with cGVHD were
pneumonia (14%), fatigue (12%), diarrhea (10%),
neutropenia (10%)*, sepsis (10%), hypokalemia (7%),
headache (5%), musculoskeletal pain (5%), and pyrexia
(5%).
Twenty-four percent of patients receiving IMBRUVICA® in the cGVHD trial discontinued treatment due to adverse reactions. Adverse reactions
leading to dose reduction occurred in 26% of
patients.
*Treatment-emergent decreases (all grades) were based on
laboratory measurements.
DRUG INTERACTIONS
CYP3A Inhibitors: Co-administration of
IMBRUVICA® with strong or moderate CYP3A inhibitors may
increase ibrutinib plasma concentrations. Dose modifications of
IMBRUVICA® may be recommended when used concomitantly
with posaconazole, voriconazole, and moderate CYP3A inhibitors.
Avoid concomitant use of other strong CYP3A inhibitors. Interrupt
IMBRUVICA® if strong inhibitors are used short-term
(e.g., for ≤ 7 days). See dose modification guidelines in USPI
sections 2.4 and 7.1.
CYP3A Inducers: Avoid coadministration with strong CYP3A
inducers.
SPECIFIC POPULATIONS
Hepatic Impairment (based on Child-Pugh criteria): Avoid
use of IMBRUVICA® in patients with severe baseline
hepatic impairment. In patients with mild or moderate impairment,
reduce IMBRUVICA® dose.
Please click here for full Prescribing
Information.
About AbbVie
AbbVie is a global, research and development-based
biopharmaceutical company committed to developing innovative
advanced therapies for some of the world's most complex and
critical conditions. The company's mission is to use its expertise,
dedicated people and unique approach to innovation to markedly
improve treatments across four primary therapeutic areas:
immunology, oncology, virology and neuroscience. In more than
75 countries, AbbVie employees are working every day to advance
health solutions for people around the world. For more information
about AbbVie, please visit us at www.abbvie.com.
Follow @abbvie on
Twitter, Facebook, LinkedIn or Instagram.
Forward-Looking Statements
Some statements in this news release may be forward-looking
statements for purposes of the Private Securities Litigation Reform
Act of 1995. The words "believe," "expect," "anticipate," "project"
and similar expressions, among others, generally identify
forward-looking statements. AbbVie cautions that these
forward-looking statements are subject to risks and uncertainties
that may cause actual results to differ materially from those
indicated in the forward-looking statements. Such risks and
uncertainties include, but are not limited to, challenges to
intellectual property, competition from other products,
difficulties inherent in the research and development process,
adverse litigation or government action, and changes to laws and
regulations applicable to our industry. Additional information
about the economic, competitive, governmental, technological and
other factors that may affect AbbVie's operations is set forth in
Item 1A, "Risk Factors," in AbbVie's 2015 Annual Report on Form
10-K, which has been filed with the Securities and Exchange
Commission. AbbVie undertakes no obligation to release publicly any
revisions to forward-looking statements as a result of subsequent
events or developments, except as required by law.
IMBRUVICA is a registered trademark of Pharmacyclics LLC.
1 Genetics Home Reference. Isolated growth
hormone deficiency.
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed October 2019.
2 Turetsky, et al. Single cell imaging of Bruton's
Tyrosine Kinase using an irreversible inhibitor. Scientific
Reports. volume 4, Article number: 4782 (2014).
3 de Rooij MF, Kuil A, Geest CR, et al. The
clinically active BTK inhibitor PCI-32765 targets B-cell receptor-
and chemokine-controlled adhesion and migration in chronic
lymphocytic leukemia. Blood. 2012;119(11):2590-2594.
4 IMBRUVICA U.S. Prescribing
Information, September 2019.
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