NORTH CHICAGO, Ill.,
Dec. 6, 2020 /PRNewswire/
-- AbbVie (NYSE: ABBV), today announced results from a
long-term integrated analysis of two Phase 3 clinical studies and
additional pooled analysis evaluating the effect of IMBRUVICA
(ibrutinib) based therapies for the first-line treatment of
high-risk patients with chronic lymphocytic leukemia (CLL). The
totality of data featured at the virtual 2020 American Society of
Hematology (ASH) Annual Meeting continues to establish the
treatment benefit of IMBRUVICA for CLL patients with or without
high-risk disease.
Results from an integrated analysis of two Phase 3 clinical
trials (RESONATE-2 and iLLUMINATE) with up to 6.5 years of
long-term follow-up investigating the use of IMBRUVICA-based
therapies in patients with CLL/small lymphocytic lymphoma (SLL)
with first-line treatment showed similar progression-free survival
(PFS) and overall response rates (ORR) in patients with or without
high-risk genomic features (Abstract #2220).1
"We're excited to present long-term follow-up results at the ASH
congress across multiple studies, including our pivotal Phase 3
clinical trials RESONATE-2 and iLLUMINATE, which showed continued
PFS and ORR benefits across high-risk patients with previously
untreated CLL," said Danelle James,
M.D., M.A.S., IMBRUVICA Clinical Development Lead, Pharmacyclics
LLC, an AbbVie company.
Additionally, a pooled analysis across four clinical trials with
up to 8 years of follow-up, including three Phase 3 studies
(RESONATE-2, iLLUMINATE, E1912), and the Phase 2 PCYC-1122e
study - sponsored by the National Heart, Lung, and Blood Institute
(NHLBI) - showed that first-line treatment with IMBRUVICA-based
therapies resulted in sustained, long-term efficacy with high
4-year PFS rates in high-risk CLL patients, defined as del(17p) or
TP53 gene mutations (Abstract 2219).2
"The presence of del(17p) or TP53 gene mutation is a strong
negative predictor of survival in patients with CLL, and testing
for these markers is important so patients receive optimal
therapy," said John Allan, M.D.,
assistant professor of medicine in the Division of Hematology and
Medical Oncology and a member of the Sandra and Edward Meyer Cancer
Center at Weill Cornell Medicine and principal study investigator
of the pooled analysis. "Although these patients remain at risk for
disease progression, first-line treatment with ibrutinib based
therapy may meaningfully improve the poor prognosis in this
high-risk population."
The informCLL™ real-world prospective observational registry
assessing treatment patterns will be featured in an oral
presentation. Data from this real-world evidence study showed low
testing rates for prognostic and biomarker features among patients
with CLL.3 Further, when biomarker testing was
performed, the selection of chemo-immunotherapy (CIT) continued for
a considerable proportion of patients with del(17p)/TP53 mutational
status, which is inconsistent with current guidelines (Abstract
547).4 As well, a retrospective, chart
review study of real world patients featured as an oral
presentation examined treatment patterns and time to next treatment
(TTNT) in patients with CLL. Results showed high-risk patients with
CLL treated with IMBRUVICA monotherapy had longer TTNT than those
treated with CIT, and that IMBRUVICA therapy showed similar results
in high risk and non-high-risk patients (Abstract
372).4
Abstract #2220: Outcomes of First-Line Ibrutinib in Patients
With Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma
(CLL/SLL) and High-Risk Genomic Features With up to 6.5 Years
Follow-up: Integrated Analysis of Two Phase 3 Studies (RESONATE-2
and iLLUMINATE)
Poster Presentation: Sunday, December
6, 2020 at 7:00 a.m.
PST
Data were presented from an integrated analysis of two Phase 3
studies evaluating IMBRUVICA-based therapy in the first-line
treatment of CLL/SLL (RESONATE-2 and iLLUMINATE) to better
understand outcomes in patients with various high-risk genomic
features, including integrated fluorescence in situ hybridization
(FISH) cytogenetics and single gene mutations.
In RESONATE-2 (NCT01722487), patients aged ≥65 years without
del(17p) were randomized to single-agent IMBRUVICA or chlorambucil.
In iLLUMINATE (NCT02264574), patients aged ≥65 years, or <65
years with coexisting conditions or del(17p)/TP53 mutation, were
randomized to IMBRUVICA plus obinutuzumab or chlorambucil plus
obinutuzumab. The integrated analysis included 498 patients treated
with first-line IMBRUVICA -based or chlorambucil-based therapy
(n=249 each) with a median follow-up of 49.1 months. At 42 months,
PFS rates were higher across high-risk genomic subgroups in
patients treated with IMBRUVICA (63 to 82 percent) compared to
those receiving chlorambucil with or without obinutuzumab (6 to 34
percent), and consistent PFS benefit with IMBRUVICA was observed
across all high-risk genomic subgroups.1 When
comparing IMBRUVICA-treated patients with specific high-risk
genomic features versus those without, results showed that PFS and
ORR were comparable in the different subgroups, including patients
with unmutated versus mutated immunoglobin heavy chain variable
(IGHV) (PFS Hazard Ratio [HR], 1.79, 95% Confidence Interval [CI]
0.99-3.24) or mutated versus not mutated NOTCH1 (PFS HR, 1.05, 95%
CI 0.65-1.69). 1 Results also showed improved
outcomes for patients with del(17p)/TP53 mutated/BIRC3
mutated, the highest risk category (HR 1.05, 95% CI
0.54-2.04). 1,[5]
At a median duration of IMBRUVICA treatment of 35.7 to 43.8
months across these high-risk subgroups, there were no meaningful
differences in the rates of treatment-emergent AEs of any grade or
Grade 3 or higher AEs compared to those of the overall
population. 1
Abstract #2219: Long-Term Efficacy of First-Line Ibrutinib
Treatment for Chronic Lymphocytic Leukemia (CLL) With 4 Years of
Follow-Up in Patients With TP53 Aberrations (del(17p) or TP53
mutation): a Pooled Analysis from 4 Clinical Trials
Poster Presentation: Sunday, December 6, 2020 at 7:00 a.m.
PST
A pooled analysis of data across four studies to evaluate the
long-term efficacy and safety of first-line IMBRUVICA-based therapy
in patients with CLL bearing TP53 aberrations were presented.
Eighty-nine patients with TP53 aberrations receiving first-line
IMBRUVICA treatment were included in this pooled analysis. Median
age was 65 years, and 69 percent of patients were male. Forty-five
patients received IMBRUVICA as a single agent and 44 patients
received IMBRUVICA in combination with an anti-CD20
agent.2
At 48 months, the PFS rate was 79 percent among these high-risk
patients treated with IMBRUVICA-based
therapy. 2 Median duration of IMBRUVICA
treatment was 46 months. With a median follow-up of 50 months,
median PFS was not reached (95% CI: 67 months to not
estimable). 2
At the current follow-up, 46 percent of patients with TP53
aberrations remained on IMBRUVICA treatment. Reasons for treatment
discontinuation were progressive disease (20 percent), study
closure (12 percent), adverse events (AEs; 10 percent), withdrawal
by patient (7 percent), death (3 percent), and other (1
percent). 2
Grade 3 or greater AEs of clinical interest with up to 8 years
of treatment with IMBRUVICA were infection (22 percent), most
commonly pneumonia (7 percent); hypertension (13 percent), atrial
fibrillation (12 percent), and major hemorrhage (7
percent).2
Abstract #547: Real-World Prognostic Biomarker Testing,
Treatment Patterns, and Dosing Among 1,461 Patients With Chronic
Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) from the
informCLL™ Prospective Observational Registry
Oral Presentation: Monday, December 7, 2020 at 8:15 a.m.
PST
Results from the informCLL™ real-world prospective
observational registry assessing treatment patterns in the era of
novel agents were presented in an oral session.
The registry fully enrolled with 1,461 patients, of whom 855 (59
percent) were previously untreated and 606 (41 percent) were
relapsed/refractory.4 Community-based practices
enrolled 93 percent of the patients. 4 Patient
demographics include a median age of 71 years; majority were male
(64 percent), and 88 percent had an ECOG performance statue of
0/1.4 Median follow-up for previously untreated
patients was 14.9 months and 15.3 months for relapsed/refractory
patients.4
Results showed the most common index treatment was IMBRUVICA;
and CIT was the next most widely used treatment regimen for
one-third of patients.4 Data also showed that
prognostic biomarker testing rates were poor, especially for TP53
and IGHV mutational status.4 Data from the informCLL
study also indicates a 'knowledge gap' in terms of importance of
prognostic marker testing and appropriate selection of therapies
for patients with high-risk disease.4
Abstract #372: Clinical Outcomes Among Real-World Patients
with Chronic Lymphocytic Leukemia (CLL) Initiating First-Line
Ibrutinib or Chemoimmunotherapy (CIT) Stratified by Risk Status:
Results from a US Retrospective Chart Review Study
Oral Presentation: Sunday, December 6, 2020 at 10:00 a.m.
PST
Results from a retrospective study comparing clinical outcomes
in high-risk and non-high-risk patients with CLL receiving
IMBRUVICA compared to those receiving chemoimmunotherapy (CIT) as
first-line therapy were presented.
The analysis was performed by evaluating medical records from
more than 40 U.S. clinical practices, included 271 patients with
high-risk disease and 245 patients with non-high-risk
CLL.3 Baseline demographics and clinical
characteristics were balanced within each pair of comparison
groups. 3 The median (range) follow-up for
high-risk patients treated with IMBRUVICA compared to CIT was 33.3
versus 35.3 months, respectively.3 Additionally, the
median (range) duration of first-line therapy for patients treated
with IMBRUVICA was 28.6 months compared to 5.5 months for patients
treated with CIT. 3
The weighted analysis showed that high-risk patients treated
with IMBRUVICA had significantly longer median TTNT and were 54
percent less likely to start a new treatment compared to high-risk
patients treated with CIT (HR [95% CI]: 0.46 [0.34-0.62],
p<0.01).3 During the available follow-up, more
weighted high-risk patients treated with IMBRUVICA had only one
line of treatment compared to weighted high-risk patients treated
with CIT (74.7% vs 47.2%, respectively); more non-high-risk CIT
patients had only one line of treatment compared to high-risk CIT
patients (69.9% vs 45.8%, respectively); and more non-high-risk
IMBRUVICA patients had only one line of treatment compared to
high-risk IMBRUVICA patients (91.5% vs 81.7%, respectively).
Additionally, the majority of patients received a small
molecular inhibitor therapy as second-line treatment. The most
common second-line agents were IMBRUVICA monotherapy in the CIT
groups (high-risk: 86.5%; non-HR: 83.7%) and venetoclax in the
patients treated with first-line IMBRUVICA, either as monotherapy
(high-risk: 37.5%; non-high-risk: 28.6%) or in combination with
rituximab (high-risk: 28.1%; non-high-risk: 28.6%).
Results from the Kaplan-Meyer analysis showed that weighted
high-risk IMBRUVICA patients had significantly longer median TTNT
and were 54 percent less likely to start a new treatment compared
to high-risk CIT patients (HR 95% CI: 0.46 [0.34-0.62]; p<0.01).
For the high-risk patients receiving CIT versus non-high-risk
patients receiving CIT, high-risk patients had a significantly
shorter median TTNT and were 2.43 times more likely to start a new
treatment (HR [95% CI]: 2.43 [1.58-3.47];
p<0.01). 3 No significant differences were
noted in TTNT between high-risk and non-high-risk groups receiving
IMBRUVICA, with median TTNT not reached (HR [95% CI]: 2.2
[0.96-4.96]; p=0.06). 3
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.6,7 By blocking BTK, IMBRUVICA may help move
abnormal B cells out of their nourishing environments in the lymph
nodes, bone marrow, and other organs.8
Since its launch in 2013, IMBRUVICA has received 11 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.9
IMBRUVICA is now approved in more than 100 countries and has
been used to treat more than 200,000 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.
In early 2019, the National Comprehensive Cancer Network®
(NCCN®<https://www.nccn.org/patients/>), a not-for-profit
alliance of 28 leading cancer centers devoted to patient care,
research, and education, recommends ibrutinib (IMBRUVICA) as a
preferred regimen for the initial treatment of CLL/SLL. In
February 2020, the NCCN Guidelines®
were updated to elevate IMBRUVICA with or without rituximab from
other recommended regimens to a preferred regimen for the treatment
of relapsed/refractory MCL. In September
2020, the NCCN guidelines were updated to elevate IMBRUVICA
with or without rituximab as the only Category 1 preferred regimen
for treatment-naïve WM patients.
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, 10 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.
What is IMBRUVICA® (ibrutinib)?
IMBRUVICA® (ibrutinib) is a prescription medicine
used to treat adults with:
- Mantle cell lymphoma (MCL) who have received at least one prior
treatment
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma
(SLL)
- Chronic lymphocytic leukemia (CLL)/Small lymphocytic lymphoma
(SLL) with 17p deletion
- Waldenström's macroglobulinemia (WM)
- Marginal zone lymphoma (MZL) who require a medicine by mouth or
injection (systemic therapy) and have received a certain type of
prior treatment
- Chronic graft versus host disease (cGVHD) after failure of 1 or
more lines of systemic therapy
It is not known if IMBRUVICA® is safe and effective
in children.
Important Side Effect Information
Before taking IMBRUVICA®, tell your
healthcare provider about all of your medical conditions,
including if you:
- have had recent surgery or plan to have surgery. Your
healthcare provider may stop IMBRUVICA® for any planned
medical, surgical, or dental procedure.
- have bleeding problems.
- have or had heart rhythm problems, smoke, or have a medical
condition that increases your risk of heart disease, such as high
blood pressure, high cholesterol, or diabetes.
- have an infection.
- have liver problems.
- are pregnant or plan to become pregnant. IMBRUVICA®
can harm your unborn baby. If you are able to become pregnant, your
healthcare provider will do a pregnancy test before starting
treatment with IMBRUVICA®. Tell your healthcare provider
if you are pregnant or think you may be pregnant during treatment
with IMBRUVICA®.
-
- Females who are able to become pregnant should use
effective birth control (contraception) during treatment with
IMBRUVICA® and for 1 month after the last dose.
- Males with female partners who are able to become
pregnant should use effective birth control, such as condoms,
during treatment with IMBRUVICA® and for 1 month after
the last dose.
- are breastfeeding or plan to breastfeed. Do not breastfeed
during treatment with IMBRUVICA® and for 1 week after
the last dose.
Tell your healthcare provider about all the medicines you
take, including prescription and over-the-counter
medicines, vitamins, and herbal supplements. Taking
IMBRUVICA® with certain other medicines may affect how
IMBRUVICA® works and can cause side effects.
How should I take IMBRUVICA®?
- Take IMBRUVICA® exactly as your healthcare provider
tells you to take it.
- Take IMBRUVICA® 1 time a day.
- Swallow IMBRUVICA® capsules or tablets whole with a
glass of water.
- Do not open, break or chew IMBRUVICA® capsules.
- Do not cut, crush or chew IMBRUVICA® tablets.
- Take IMBRUVICA® at about the same time each
day.
- If you miss a dose of IMBRUVICA® take it as soon as
you remember on the same day. Take your next dose of
IMBRUVICA® at your regular time on the next day. Do not
take extra doses of IMBRUVICA® to make up for a missed
dose.
- If you take too much IMBRUVICA® call your healthcare
provider or go to the nearest hospital emergency room right
away.
What should I avoid while taking
IMBRUVICA®?
- You should not drink grapefruit juice, eat grapefruit, or eat
Seville oranges (often used in
marmalades) during treatment with IMBRUVICA®. These
products may increase the amount of IMBRUVICA® in your
blood.
What are the possible side effects of
IMBRUVICA®?
IMBRUVICA® may cause serious side
effects, including:
- Bleeding problems (hemorrhage) are common
during treatment with IMBRUVICA®, and can also be
serious and may lead to death. Your risk of bleeding may increase
if you are also taking a blood thinner medicine. Tell your
healthcare provider if you have any signs of bleeding, including:
blood in your stools or black stools (looks like tar), pink or
brown urine, unexpected bleeding, or bleeding that is severe or
that you cannot control, vomit blood or vomit looks like coffee
grounds, cough up blood or blood clots, increased bruising,
dizziness, weakness, confusion, change in your speech, or a
headache that lasts a long time or severe headache.
- Infections can happen during treatment with
IMBRUVICA®. These infections can be serious and
may lead to death. Tell your healthcare provider right away if you
have fever, chills, weakness, confusion, or other signs or symptoms
of an infection during treatment with IMBRUVICA®.
- Decrease in blood cell counts. Decreased blood
counts (white blood cells, platelets, and red blood cells) are
common with IMBRUVICA®, but can also be severe.
Your healthcare provider should do monthly blood tests to check
your blood counts.
- Heart rhythm problems (ventricular arrhythmias, atrial
fibrillation and atrial flutter). Serious heart rhythm problems
and death have happened in people treated with
IMBRUVICA®, especially in people who have an increased
risk for heart disease, have an infection, or who have had heart
rhythm problems in the past. Tell your healthcare provider if you
get any symptoms of heart rhythm problems, such as feeling as if
your heart is beating fast and irregular, lightheadedness,
dizziness, shortness of breath, chest discomfort, or you
faint. If you develop any of these symptoms, your healthcare
provider may do a test to check your heart (ECG) and may change
your IMBRUVICA® dose.
- High blood pressure (hypertension). New or
worsening high blood pressure has happened in people treated with
IMBRUVICA®. Your healthcare provider may start you on
blood pressure medicine or change current medicines to treat your
blood pressure.
- Second primary cancers. New cancers have happened
during treatment with IMBRUVICA®, including cancers of
the skin or other organs.
- Tumor lysis syndrome (TLS). TLS is caused by the fast
breakdown of cancer cells. TLS can cause kidney failure and the
need for dialysis treatment, abnormal heart rhythm, seizure, and
sometimes death. Your healthcare provider may do blood tests to
check you for TLS.
The most common side effects of
IMBRUVICA® in adults with B-cell
malignancies (MCL, CLL/SLL, WM and MZL) include:
The most common side effects of
IMBRUVICA® in adults with cGVHD
include:
Diarrhea is a common side effect in people who take
IMBRUVICA®. Drink plenty of fluids during
treatment with IMBRUVICA® to help reduce
your risk of losing too much fluid (dehydration) due to diarrhea.
Tell your healthcare provider if you have diarrhea that does not go
away.
These are not all the possible side effects of
IMBRUVICA®. Call your doctor for medical advice about
side effects. You may report side effects to FDA at
1-800-FDA-1088.
General information about the safe and effective use of
IMBRUVICA®
Medicines are sometimes prescribed for purposes other than those
listed in a Patient Information leaflet. Do not use
IMBRUVICA® for a condition for which it was not
prescribed. Do not give IMBRUVICA® to other people, even
if they have the same symptoms that you have. It may harm them. You
can ask your pharmacist or healthcare provider for information
about IMBRUVICA® that is written for health
professionals.
Please
click here for full Prescribing Information.
About AbbVie in Oncology
At AbbVie, we are committed to transforming standards of care for
multiple blood cancers while advancing a dynamic pipeline of
investigational therapies across a range of cancer types. Our
dedicated and experienced team joins forces with innovative
partners to accelerate the delivery of potentially breakthrough
medicines. We are evaluating more than 20 investigational medicines
in over 300 clinical trials across some of the world's most
widespread and debilitating cancers. As we work to have a
remarkable impact on people's lives, we are committed to exploring
solutions to help patients obtain access to our cancer medicines.
For more information, please
visit http://www.abbvie.com/oncology
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.
Dr. John Allan has been a paid
speaker and advisory board member for AbbVie, and a paid speaker
for Janssen Pharmaceutical Company and Pharmacyclics.
Dr. John Allan has been a paid
speaker and advisory board member for AbbVie, and a paid speaker
for Janssen Pharmaceutical Company and Pharmacyclics.
IMBRUVICA is a registered trademark of Pharmacyclics LLC.
SOURCE AbbVie Inc.
1Burger JA. et al. Outcomes of first-line ibrutinib
in patients with chronic lymphocytic leukemia/small lymphocytic
lymphoma (CLL/SLL) and high-risk genomic features with up to 6.5
years follow-up: integrated analysis of two phase 3 studies
(RESONATE-2 and iLLUMINATE). 2020 American Society of Hematology
Annual Meeting. December 2020.
2Allan JN. et al. Long-term efficacy of first-line
ibrutinib treatment for chronic lymphocytic leukemia (CLL) with 4
years of follow-up in patients with TP53 aberrations (del(17p) or
TP53 mutation): a pooled analysis from 4 clinical trials. 2020
American Society of Hematology Annual Meeting. December 2020.
3Mato A. et al. Real-world prognostic biomarker
testing, treatment patterns and dosing among 1461 patients (pts)
with chronic lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL) from the informCLL™ prospective observational registry.
2020 American Society of Hematology Annual Meeting.
December 2020.
4Huang Q. et al. Clinical outcomes among real-world
patients with chronic lymphocytic leukemia (CLL) initiating
first-line ibrutinib or chemoimmunotherapy stratified by risk
status: results from a US retrospective chart review study. 2020
American Society of Hematology Annual Meeting. December 2020.
5Rossi, D. et al. Integrated mutational and
cytogenetic analysis identifies new prognostic subgroups in chronic
lymphocytic leukemia. Blood. 2013;121(8):1403–1412.
6Genetics Home Reference. Isolated growth hormone
deficiency.
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed January 2020.
7Turetsky, et al. Single cell imaging of Bruton's
Tyrosine Kinase using an irreversible inhibitor. Scientific
Reports. volume 4, Article number: 4782 (2014).
8de 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.
9IMBRUVICA U.S. Prescribing Information, April 2020.
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SOURCE AbbVie