RESONATE TM -2 FRONTLINE DATA
RESONATE TM -2 was a multicenter, randomized 1:1, open-label, Phase 3 trial of IMBRUVICA® vs chlorambucil
in frontline CLL/SLL patients ≥65 years (N=269) 2,3 Patients with 17p deletion were excluded 3
EXTENDED
OVERALL SURVIVAL 2
PROLONGED
PROGRESSION-FREE SURVIVAL 2,3
SECONDARY ENDPOINT: OS
IMBRUVICA® vs CHLORAMBUCIL
PRIMARY ENDPOINT: PFS
IMBRUVICA® vs CHLORAMBUCIL
84% statistically significant reduction
in risk of progression or death 2,3
Reduced risk of death by more than half
Estimated PFS at 18 months
90 % IMBRUVICA®
100
56%
Estimated survival rates
at 24 months
IMBRUVICA ®
(95% CI: 89, 97)
90
80
70
95%
Statistically
significant
reduction in
risk of death
HR=0.44
(95% CI: 0.21, 0.92)
60
50
40
30
41%
of patients
crossed over
to IMBRUVICA®
upon disease
progression
chlorambucil
(95% CI: 77, 90)
84%
Estimated PFS at 18 months
20
52 % Chlorambucil
10
HR=0.16 (95% CI: 0.09, 0.28); P<0.0001
0
0
3
6
9
12
• Median follow-up was 28 months 2
• Fewer deaths with IMBRUVICA® were observed; 11 (8.1%) in the IMBRUVICA®
arm vs 21 (15.8%) in the chlorambucil arm 2
15
18
21
24
27
Months
N at risk
IMB 136 133 130 126 122 98 66 21 2 0
CLB 133 121 95 85 74 49 34 10 0 0
• Median follow-up was 18 months 3
• With IMBRUVICA®, median PFS was not reached vs 18.9 months
(95% CI: 14.1, 22.0) with chlorambucil 2
• PFS and ORR (CR and PR) were assessed by an IRC according to
the revised 2008 iwCLL criteria 3
RESONATE™-2 Adverse Reactions ≥15%
• Diarrhea (42%)
• Musculoskeletal pain (36%)
• Cough (22%)
• Rash (21%)
• Bruising (19%)
• Peripheral edema (19%)
• Pyrexia (17%)
• Dry eye (17%)
• Arthralgia (16%)
• Skin infection (15%)
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 (62%), neutropenia (61%), diarrhea (43%), anemia (41%),
musculoskeletal pain (30%), rash (30%), bruising (30%), nausea (29%), fatigue
(29%), hemorrhage (22%), and pyrexia (21%).
The most common Grade 3 or 4 adverse reactions (≥5%) in patients with
B-cell malignancies (MCL, CLL/SLL, WM and MZL) were neutropenia (39%),
thrombocytopenia (16%), and pneumonia (10%).
Approximately 6% (CLL/SLL), 14% (MCL), 11% (WM) and 10% (MZL) of
patients had a dose reduction due to adverse reactions. Approximately 4%-
10% (CLL/SLL), 9% (MCL), and 9 % (WM [6%] 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 4 adverse reactions (≥5%) reported in
patients with cGVHD were fatigue (12%), diarrhea (10%), neutropenia
(10%), pneumonia (10%), sepsis (10%), hypokalemia (7%), headache (5%),
musculoskeletal pain (5%), and pyrexia (5%).
To learn more, visit
IMBRUVICAHCP.com
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.
DRUG INTERACTIONS
CYP3A Inducers: Avoid coadministration with strong CYP3A inducers.
CYP3A Inhibitors: Dose adjustment may be recommended.
SPECIFIC POPULATION S
Hepatic Impairment (based on Child-Pugh criteria): Avoid use of
IMBRUVICA ® in patients with moderate or severe baseline hepatic impairment.
In patients with mild impairment, reduce IMBRUVICA ® dose.
Please see the Brief Summary on the following pages.
CI=confi dence interval, CLL=chronic lymphocytic leukemia, HR=hazard ratio, IRC=Independent Review
Committee, iwCLL=International Workshop on CLL, OS=overall survival, PFS=progression-free survival,
SLL=small lymphocytic lymphoma.
References: 1. Data on fi le. Pharmacyclics LLC. 2. IMBRUVICA ® (ibrutinib)
Prescribing Information. Pharmacyclics LLC 2017. 3. Burger JA, Tedeschi A, Barr
PM, et al; for the RESONATE-2 Investigators. Ibrutinib as initial therapy for patients
with chronic lymphocytic leukemia. N Engl J Med. 2015;373(25):2425-2437.