ASH Clinical News ACN_5.6_SUPP_DIGITAL_correction_p20 | Page 11

RESONATE™-2 PRIMARY ENDPOINT: PFS WITH IMBRUVICA® VS CHLORAMBUCIL 3
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
Primary analysis: Superior PFS by IRC assessment with
IMBRUVICA® with a median follow-up of 18 months 2,3
84% statistically significant reduction
in risk of progression or death 2,3
OVERALL FOLLOW-UP OF 55 MONTHS
Long-term follow-up: Investigator-assessed median
PFS was not reached with IMBRUVICA® with an overall
follow-up of 55 months 1,2
Investigator-assessed long-term follow-up
of risk of disease progression or death 1
90% of patients estimated
100
to be progression free and alive
at 18 months
100
80
IMBRUVICA®
IMBRUVICA®
80
60
40
52% of patients estimated to
Median PFS was NR
60
40
be progression free and alive at
18 months
20
HR=0.16 (95% CI: 0.09, 0.28); P<0.0001
0
15
chlorambucil
0 3 6 9 12 IMB 136 133 130 126 122 98 66
18
21
21
2
24
27
0
CLB 133 121 95 85 74 49 34 10 0 0
0
Months
N at risk
0
Secondary endpoint: OS with IMBRUVICA® vs chlorambucil 2,3
Based on a median follow-up of 28 months, IMBRUVICA® resulted
in a 56% statistically signifi cant reduction in the risk of death vs
chlorambucil (HR=0.44 [95% CI: 0.21, 0.92]) 1
• The estimated survival rate at 24 months was 95% with IMBRUVICA®
(95% CI: 89, 97) vs 84% with chlorambucil (95% CI: 77, 90)
• 41% of chlorambucil-treated patients crossed over to IMBRUVICA®
upon disease progression
RESONATE™-2 Adverse Reactions ≥15%
• Diarrhea (42%)
• Musculoskeletal pain ‡ (36%)
• Cough (22%)
chlorambucil
20
Median PFS was 18.9 (95% CI: 14, 22)
ADVERSE REACTIONS
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% of patients discontinued IMBRUVICA ® due to adverse
reactions. Adverse reactions leading to discontinuation included
pneumonia (1.1%), hemorrhage (1%), atrial fi brillation (0.9%), rash (0.7%),
diarrhea (0.6%), neutropenia (0.5%), sepsis (0.4%), thrombocytopenia (0.4%),
interstitial lung disease (0.3%), and bruising (0.2%). Nine percent of patients
had a dose reduction due to adverse reactions.
*Treatment-emergent decreases (all grades) were based on laboratory measurements.
To learn more, visit
IMBRUVICAHCP.com
© Pharmacyclics LLC 2019 © Janssen Biotech, Inc. 2019 04/19 PRC-05156a
6
9
12
15
18
21
24
27
30
33 36
39
42
45
48
51
54 57
11 3
Median PFS was not reached with IMBRUVICA® with an overall
follow-up of 55 months 1,2 :
• Median time on study was 48.1 months (0.1 - 55.2 months)
• 74% of patients estimated to be progression free and alive at
4 years in the IMBRUVICA® arm (95% CI: 65, 81)
• 16% of patients estimated to be progression free and alive at
4 years in the chlorambucil arm (95% CI: 9, 24)
• 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.
3
Months
N at risk
136 133 129 126 124 123 121 118 112 109 108 104 103 101 98 65 45
IMB
133 121 88 78 69 61 57 49 41 33 33 31 30 25 23 10 5
CLB
Complete long-term
follow-up results
are not included
in the Prescribing
Information for
IMBRUVICA®. The
timing for long-term
follow-up was
not prespecifi ed
and the analysis
was descriptive in
nature.
• Pyrexia (17%)
• Dry eye (17%)
• Arthralgia (16%)
• Skin infection ‡ (15%)
‡
Includes multiple ADR terms.
DRUG INTERACTIONS
CYP3A Inhibitors: Modify IMBRUVICA ® dose as described 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 see the Brief Summary on the following pages.
CI=confi dence interval, CLB=chlorambucil, CLL=chronic lymphocytic leukemia,
HR=hazard ratio, IRC=Independent Review Committee, IMB=IMBRUVICA ® ,
NR=not reached, 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. 2019. 3. Burger JA, Tedeschi A, Barr PM, et al.
Ibrutinib as initial therapy for patients with chronic lymphocytic leukemia. N Engl J Med.
2015;373(25):2425-2437.