NORTH CHICAGO, Ill.,
June 4, 2021 /PRNewswire/
-- AbbVie (NYSE: ABBV), today announced extended
long-term data from the Phase 3 RESONATE-2 study (PCYC-1115/1116)
evaluating single-agent IMBRUVICA (ibrutinib) versus chlorambucil
with up to seven years of follow-up in patients with chronic
lymphocytic leukemia/small lymphocytic lymphoma
(CLL/SLL).1 These data will be presented on June 4th during the 2021 American
Society of Clinical Oncology (ASCO) Annual Meeting (Abstract
#7523). Additionally, new data will be presented during the
European Hematology Association (EHA) Virtual Congress from
June 9-17, including findings from
the informCLL™ real-world prospective observational registry
assessing how real-world treatment patterns align with National
Comprehensive Cancer Network (NCCN®)-recommended
regimens for CLL/SLL.
"These data add to the overall body of evidence that patients
treated with ibrutinib can achieve extended progression-free
survival and overall survival when used as a first-line therapy,"
said Paul M. Barr, M.D., lead study
investigator of the Phase 3 RESONATE-2 trial, and Professor of
Medicine at the Wilmot Cancer Institute, University of Rochester. "The results add to the
extensive clinical evidence supporting the use of single-agent
ibrutinib for long-term disease control."
The RESONATE-2 study evaluated 269 patients 65 years or older
with previously untreated CLL/SLL, without 17p deletion, who
received continuous single-agent IMBRUVICA until progression or
chlorambucil up to 12 cycles.1 With up to seven
years of follow-up, progression-free survival (PFS) benefit with
single-agent IMBRUVICA was sustained (Hazard Ratio [HR] 0.160 [95
percent Confidence Interval (CI):
0.111–0.230]).1 At 6.5 years of follow-up, median
PFS in the IMBRUVICA treatment arm was not reached: the PFS rate
for patients treated with single-agent IMBRUVICA was 61 percent
compared with only nine percent in patients treated with
chlorambucil.1 Additionally, at 6.5 years, the
IMBRUVICA treatment arm showed an overall survival (OS) rate of 78
percent; OS was not captured for the chlorambucil treatment arm for
patients with disease progression after a median of five years of
follow-up.1 In this latest follow-up, the overall
response rate (ORR) was 92 percent.1
With up to seven years of follow-up, the complete response
(CR)/complete response increase (CRi) rate increased over time to
34 percent; median duration of response (range, <0.1 to 83) and
CR (range, <0.1 to 79 months) were not
reached.1 With up to seven years of follow-up,
nearly half of patients remained on long-term continuous treatment
with IMBRUVICA.1
IMBRUVICA was well tolerated as a long-term treatment and rates
of discontinuation due to AEs remained low, with 23 percent of
patients in the IMBRUVICA arm discontinuing treatment due to AEs as
the primary reason.1 Ongoing rates of Grade 3 or
higher AEs of interest remained low for hypertension
(five-to-six-year interval: n=20; six-to-seven-year interval: n=15)
and atrial fibrillation (five-to-six-year interval: n=7;
six-to-seven-year interval: n=5).1 Across full
follow-up, 31 patients had dose reductions due to any-grade
AEs.1 Of the patients who had a dose reduction, 71
percent had resolution or improvement of the
AE.1
"With long-term safety and efficacy data for IMBRUVICA in CLL,
these latest data from the RESONATE-2 study further reinforce
IMBRUVICA as a standard of care that can help patients live longer
without chemotherapy," said Danelle
James, M.D., M.A.S., Imbruvica Global Development Lead,
Pharmacyclics LLC, an AbbVie company. "These findings show
single-agent IMBRUVICA provides long-lasting, durable responses and
extended survival benefits in CLL. IMBRUVICA has a well-known
safety profile in patients with CLL, including hard-to-treat
subtypes."
The pivotal Phase 3 RESONATE-2 study served as the basis for the
FDA approval of IMBRUVICA as a single-agent in first-line treatment
for CLL/SLL in 2016, following initial approval for
relapsed/refractory (R/R) patients in 2014 based on the RESONATE
study.2
(Abstract EP635) Real-World Application of NCCN
Clinical Practice Guidelines (NCCN Guidelines®) for
CLL/SLL from the informCLL Prospective Observational
Registry
Results from the informCLL™ real-world registry assessing
treatment alignment with NCCN Guidelines® will be
presented as a poster during the EHA Virtual Congress on June
11th.
The informCLL™ registry enrolled 1,462 patients, of whom 58
percent were previously untreated and 42 percent were relapsed or
refractory. Community-based practices enrolled 93 percent of the
patients.3 The median age was 71 years, and the
median Charlson Comorbidity Index (CCI) was one with 16 percent
having a CCI >3. Single-agent ibrutinib was the most common
treatment across line of therapy at enrollment. For this analysis,
NCCN Guidelines® for CLL/SLL V.2.2017 were
used given 74 percent enrollment in 2017.3
The latest analysis showed that a third of high-risk patients
with 17p deletion/TP53 mutation, who typically have poor
outcomes after chemoimmunotherapy (CIT), did not receive
NCCN®-recommended regimens.3 Most
patients without 17p deletion/TP53 mutation received
recommended therapy across age/comorbidity
groups.3 Despite guideline recommendations for
prognostic testing, the majority of patients in the registry were
not tested for both 17p deletion/TP53 mutation and therefore
may have received suboptimal treatment with
CIT.3 These results underscore the importance of
prognostic marker testing and appropriate selection of therapies
based on NCCN Guidelines® recommendations, especially in
the community setting.3
About IMBRUVICA®
IMBRUVICA (ibrutinib) is a once-daily, first-in-class BTK
inhibitor that is administered orally, and is jointly developed and
commercialized by Pharmacyclics, LLC, an AbbVie Company, and
Janssen Biotech, Inc. (Janssen). 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.4,5 By
blocking BTK, IMBRUVICA may help move abnormal B cells out of their
nourishing environments in the lymph nodes, bone marrow, and other
organs.6
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 macroglobulinemia; 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.7
IMBRUVICA® is now approved in 101
countries and has been used to treat more than 230,000 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.
Since 2019, the National Comprehensive Cancer
Network® (NCCN®), 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 and has Category 1 treatment status
for treatment-naïve patients without deletion 17p. In January
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, regardless of duration of response to
prior chemoimmunotherapy. As of September 2020, the NCCN
guidelines were updated to reflect
IMBRUVICA® with or without rituximab as the
only Category 1 preferred regimen for both untreated and previously
treated 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, 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 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 problems. Serious heart rhythm problems
(ventricular arrhythmias, atrial fibrillation, and atrial flutter),
heart failure, 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 problems, such as feeling as if your
heart is beating fast and irregular, lightheadedness, dizziness,
shortness of breath, swelling of the feet, ankles, or legs, 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:
- diarrhea
- tiredness
- muscle and bone pain
- rash
- bruising
The most common side effects of IMBRUVICA® in
adults with cGVHD include:
- tiredness
- bruising
- diarrhea
- mouth sores (stomatitis)
- muscle spasms
- nausea
- pneumonia
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
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 are, or may be considered, 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, competition from
other products, challenges to intellectual property, 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," of AbbVie's 2018 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.
SOURCE AbbVie Inc.
|
|
|
1 Barr P.,
et al. Up to 7 Years of Follow-up in the RESONATE-2 Study of
First-Line Ibrutinib Treatment for Patients With Chronic
Lymphocytic Leukemia. 2021 American Society of Clinical Oncology
Annual Meeting. June 4-8, 2021.
|
2
IMBRUVICA U.S. Prescribing Information, December 2020.
|
3
Barrientos J.C. et. al. Real-World Application of National
Comprehensive Cancer Network Clinical Practice Guidelines In
Oncology (NCCN Guidelines®) For CLL/SLL from the informCLL
Registry. European Heamtology Association 2021 Virtual
Congress.
|
4 Genetics
Home Reference. Isolated growth hormone deficiency.
http://ghr.nlm.nih.gov/condition/isolated-growth-hormone-deficiency.
Accessed November 2020.
|
5
Turetsky, et al. Single cell imaging of Bruton's Tyrosine Kinase
using an irreversible inhibitor. Scientific Reports. volume 4,
Article number: 4782 (2014)
|
6 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.
|
7
IMBRUVICA U.S. Prescribing Information, April 2020.
|
View original
content:http://www.prnewswire.com/news-releases/results-from-imbruvica-ibrutinib-resonate-2-study-provide-up-to-seven-years-of-progression-free-and-overall-survival-data-in-first-line-chronic-lymphocytic-leukemia-cll-301306012.html
SOURCE AbbVie