ASH Clinical News ACN_4.4_SUPP_Digital Version | Page 33

RESONATE TM -2 FRONTLINE DATA
RESONATE -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
TM
PROLONGED
PROGRESSION-FREE SURVIVAL 2,3
EXTENDED
OVERALL SURVIVAL 2
PRIMARY ENDPOINT: PFS
IMBRUVICA® vs CHLORAMBUCIL
SECONDARY ENDPOINT: OS
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%
90
80
70
IMBRUVICA ®
(95% CI: 89, 97)
95%
Statistically
significant
reduction in
risk of death
Estimated survival rates
at 24 months
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
RESONATE™-2 Adverse Reactions ≥15%
• Diarrhea (42%)
• Musculoskeletal pain (36%)
• Cough (22%)
ADVERSE REACTIONS
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%),
bruising (30%), rash (30%), fatigue (29%), nausea (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% of patients discontinued IMBRUVICA ® due to adverse
reactions. Adverse reactions leading to discontinuation included hemorrhage
(1.3%), pneumonia (1.1%), atrial fi brillation (0.8%), neutropenia (0.7%)*,
rash (0.7%), diarrhea (0.6%), bruising (0.2%), interstitial lung disease (0.2%),
and thrombocytopenia (0.2%)*. Seven percent of patients had a dose reduction
due to adverse reactions.
* Treatment-emergent decreases (all grades) were based on laboratory measurements and adverse
reactions.
To learn more, visit
IMBRUVICAHCP.com
© Pharmacyclics LLC 2018 © Janssen Biotech, Inc. 2018 02/18 PRC-03863
18
21
24
27
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
• Rash (21%)
• Bruising (19%)
• Peripheral edema (19%)
Embryo-Fetal Toxicity: Based on fi ndings 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.
15
Months
N at risk
• Pyrexia (17%)
• Dry eye (17%)
• Arthralgia (16%)
• Skin infection (15%)
DRUG INTERACTIONS
CYP3A Inhibitors: Dose adjustments may be recommended.
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 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.