ASH News Daily 2017 - Issue 3 - B-15
K
Nasopharyngitis
63 (16)
0
43 (11)
0
Bronchitis
54 (14)
5 (1)
39 (10)
2 (1)
Pneumoniaa
54 (14)
35 (9)
43 (11)
27 (7)
Hypokalemia
78 (20)
22 (6)
35 (9)
12 (3)
Hypocalcemia
55 (14)
10 (3)
39 (10)
5 (1)
Hyperglycemia
43 (11)
18 (5)
33 (9)
15 (4)
Metabolism and Nutrition Disorders
Musculoskeletal and Connective Tissue Disorders
Muscle spasms
88 (22)
3 (1)
73 (19)
3 (1)
43 (11)
7 (2)
37 (10)
4 (1)
63 (16)
6 (2)
50 (13)
8 (2)
91 (23)
2 (1)
52 (13)
0
70 (18)
9 (2)
58 (15)
6 (2)
45 (12)
5 (1)
53 (14)
5 (1)
Embolic and thrombotic events venouse
49 (13)
16 (4)
22 (6)
9 (2)
Hypertensionf
41 (11)
12 (3)
15 (4)
4 (1)
Nervous System Disorders
Peripheral neuropathiesb
Psychiatric Disorders
Insomnia
Respiratory, Thoracic, and Mediastinal Disorders
Coughc
Dyspnea
d
Skin and Subcutaneous Tissue Disorders
Rash
Vascular Disorders
KRd = Kyprolis, lenalidomide, and dexamethasone; Rd = lenalidomide and dexamethasone.
a
Pneumonia includes pneumonia and bronchopneumonia.
b
Peripheral neuropathies includes peripheral neuropathy, peripheral sensory neuropathy, and peripheral
motor neuropathy.
c
Cough includes cough and productive cough.
d
Dyspnea includes dyspnea and dyspnea exertional.
e
Embolic and thrombotic events, venous include deep vein thrombosis, pulmonary embolism,
thrombophlebitis superficial, thrombophlebitis, venous thrombosis limb, post thrombotic syndrome,
venous thrombosis.
f
Hypertension includes hypertension, hypertensive crisis.
There were 274 (70%) patients in the KRd arm who received treatment beyond Cycle 12. There were no new
clinically relevant adverse reactions that emerged in the later treatment cycles.
Grade 3 and higher adverse reactions that occurred during Cycles 1-12 with a substantial difference (≥ 2%)
between the two arms were neutropenia, thrombocytopenia, hypokalemia, and hypophosphatemia.
Safety Experience with Kyprolis in Combination with Dexamethasone in Patients with Multiple Myeloma
The safety of Kyprolis in combination with dexamethasone was evaluated in an open-label, randomized trial
of patients with relapsed multiple myeloma. Patients received treatment for a median duration of 40 weeks
in the Kyprolis/dexamethasone (Kd) arm and 27 weeks in the bortezomib/dexamethasone (Vd) arm.
Deaths due to adverse reactions within 30 days of last study treatment occurred in 22/463 (5%) patients
in the Kd arm and 21/456 (5%) patients in the Vd arm. The causes of death occurring in patients (%) in
the two arms (Kd vs. Vd) included cardiac 7 (2%) versus 5 (1%), infections 5 (1%) versus 8 (2%), disease
progression 6 (1%) versus 4 (1%), pulmonary 3 (1%) versus 2 (< 1%), renal 1 (< 1%) versus 0 (0%), and
other adverse events 2 (< 1%) versus 2 (< 1%). Serious adverse reactions were reported in 48% of the
patients in the Kd arm and 36% of the patients in the Vd arm. In both treatment arms, pneumonia was
the most commonly reported serious adverse reaction (6% vs. 9%). Discontinuation due to any adverse
reaction occurred in 20% in the Kd arm versus 21% in the Vd arm. The most common reaction leading to
discontinuation was cardiac failure in the Kd arm (n = 6, 1.3%) and peripheral neuropathy in the Vd arm
(n = 19, 4.2%).
Most Common Adverse Reactions (≥ 10% in the Kd Arm) Occurring in Months 1-6 (20/56 mg/m2
Regimen in Combination with Dexamethasone)
Kd
(N = 463), n (%)
Adverse Reaction by Body System
Vd
(N = 456), n (%)
Any Grade
≥ Grade 3
Any Grade
≥ Grade 3
Anemia
160 (35)
57 (12)
112 (25)
43 (9)
Thrombocytopeniaa
127 (27)
46 (10)
112 (25)
65 (14)
Diarrhea
111 (24)
14 (3)
150 (33)
26 (6)
Nausea
69 (15)
4 (1)
66 (15)
3 (1)
Constipation
58 (13)
1 (0)
109 (24)
6 (1)
Vomiting
45 (10)
5 (1)
32 (7)
3 (1)
Blood and Lymphatic System Disorders
Gastrointestinal Disorders
General Disorders and Administration Site Conditions
Fatigue
112 (24)
13 (3)
124 (27)
25 (6)
Pyrexia
102 (22)
9 (2)
52 (11)
3 (1)
Peripheral edema
75 (16)
3 (1)
73 (16)
3 (1)
Asthenia
71 (15)
9 (2)
66 (14)
13 (3)
Upper respiratory tract infection
66 (14)
4 (1)
54 (12)
3 (1)
Bronchitis
54 (12)
5 (1)
26 (6)
2 (0)
Nasopharyngitis
45 (10)
0 (0)
42 (9)
1 (0)
Infections and Infestations
Musculoskeletal and Connective Tissue Disorders
Muscle spasms
66 (14)
1 (0)
22 (5)
3 (1)
Back pain
58 (13)
7 (2)
60 (13)
8 (2)
Headache
68 (15)
4 (1)
38 (8)
2 (0)
Peripheral neuropathiesb
54 (12)
7 (2)
167 (37)
23 (5)
Nervous System Disorders
RIGHT
Psychiatric Disorders
Insomnia
103 (22)
5 (1)
113 (25)
10 (2)
Respiratory, Thoracic, and Mediastinal Disorders
Dyspneac
123 (27)
23 (5)
66 (15)
8 (2)
Cough
91 (20)
0 (0)
61 (13)
2 (0)
80 (17)
29 (6)
33 (7)
12 (3)
d
Vascular Disorders
Hypertensione
Kd = Kyprolis and dexamethasone; Vd = bortezomib and dexamethasone.
a
Thrombocytopenia includes platelet count decreased and thrombocytopenia.
b
Peripheral neuropathies include peripheral neuropathy, peripheral sensory neuropathy, and peripheral
motor neuropathy.
c
Dyspnea includes dyspnea and dyspnea exertional.
d
Cough includes cough and productive cough.
e
Hypertension includes hypertension, hypertensive crisis, and hypertensive emergency.
The event rate of ≥ Grade 2 peripheral neuropathy in the Kd arm was 6% (95% CI: 4, 8) versus 32%
(95% CI: 28, 36) in the Vd arm.
6.2 Postmarketing Experience
The following additional adverse reactions were reported in the postmarketing experience with Kyprolis.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always
possible to reliably estimate their frequency or establish a causal relationship to drug exposure: hemolytic
uremic syndrome (HUS), gastrointestinal perforation, pericarditis.
8. USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
Risk Summary
Kyprolis can cause fetal harm based on findings from animal studies and the drug's mechanism of action.
There are no adequate and well-controlled studies in pregnant women using Kyprolis.
Females of reproductive potential should be advised to avoid becoming pregnant while being treated
with Kyprolis. Males of reproductive potential should be advised to avoid fathering a child while being
treated with Kyprolis. Consider the benefits and risks of Kyprolis and possible risks to the fetus when
prescribing Kyprolis to a pregnant woman. If Kyprolis is used during pregnancy, or if the patient becomes
pregnant while taking this drug, apprise the patient of the potential hazard to the fetus. In the U.S. general
population, the estimated background risk of major birth defects and miscarriage in clinically recognized
pregnancies is 2%-4% and 15%-20%, respectively.
8.2 Lactation
Risk Summary
There is no information regarding the presence of Kyprolis in human milk, the effects on the breastfed
infant, or the effects on milk production. The developmental and health benefits of breastfeeding should
be considered along with the mother's clinical need for Kyprolis and any potential adverse effects on the
breastfed infant from Kyprolis or from the underlying maternal condition.
8.3 Females and Males of Reproductive Potential
Contraception
Kyprolis can cause fetal harm. Advise female patients of reproductive potential to use effective
contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment with Kyprolis
and for at least 30 days following completion of therapy. Advise male patients of reproductive potential
to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during
treatment with Kyprolis and for at least 90 days following completion of therapy.
8.4 Pediatric Use
The safety and effectiveness of Kyprolis in pediatric patients have not been established.
8.5 Geriatric Use
Of 598 patients in clinical studies of Kyprolis monotherapy dosed at 20/27 mg/m2 by up to 10-minute
infusion, 49% were 65 and over, while 16% were 75 and over. The incidence of serious adverse events was
44% in patients < 65 years of age, 55% in patients 65 to 74 years of age, and 56% in patients ≥ 75 years
of age. In a single-arm, multicenter clinical trial of Kyprolis monotherapy dosed at 20/27 mg/m2 (N = 266),
no overall differences in effectiveness were observed between older and younger patients.
Of 392 patients treated with Kyprolis in combination with lenalidomide and dexamethasone, 47% were 65
and over and 11% were 75 years and over. The incidence of serious adverse events was 50% in patients
< 65 years of age, 70% in patients 65 to 74 years of age, and 74% in patients ≥ 75 years of age. No overall
differences in effectiveness were observed between older and younger patients.
Of 463 patients treated with Kyprolis dosed at 20/56 mg/m2 by 30-minute infusion in combination with
dexamethasone, 52% were 65 and over and 17% were 75 and over. The incidence of serious adverse events
was 44% in patients < 65 years of age, 50% in patients 65 to 74 years of age, and 57% in patients ≥ 75
years of age. No overall differences in effectiveness were observed between older and younger patients.
8.6 Hepatic Impairment
Reduce the dose of Kyprolis by 25% in patients with mild or moderate hepatic impairment. Dosing
recommendation cannot be made for patients with severe hepatic function.
The pharmacokinetics and safety of Kyprolis were evaluated in patients with advanced malignancies who
had either normal hepatic function, or mild (bilirubin > 1 to 1.5×ULN or AST > ULN), moderate (bilirubin
> 1.5 to 3×ULN), or severe (bilirubin > 3×ULN) hepatic impairment. The AUC of carfilzomib increased
by approximately 50% in patients with mild and moderate hepatic impairment compared to patients
with normal hepatic function. PK data were not collected in patients with severe hepatic impairment.
The incidence of serious adverse events was higher in patients with mild, moderate, and severe hepatic
impairment combined (22/35 or 63%) than in patients with normal hepatic function (3/11 or 27%).
Monitor liver enzymes regularly, regardless of baseline values, and modify dose based on toxicity.
8.7 Renal Impairment
No starting dose adjustment is required in patients with baseline mild, moderate, or severe renal
impairment or patients on chronic hemodialysis. The pharmacokinetics and safety of Kyprolis were
evaluated in a Phase 2 trial in patients with normal renal function and those with mild, moderate, and
severe renal impairment and patients on chronic hemodialysis. In addition, a pharmacokinetic study was
conducted in patients with normal renal function and end-stage renal disease (ESRD).
In these studies, the pharmacokinetics of Kyprolis was not influenced by the degree of baseline renal
impairment, including the patients on hemodialysis. Since dialysis clearance of Kyprolis concentrations
has not been studied, the drug should be administered after the hemodialysis procedure.
The risk information provided here is not comprehensive. The FDA-approved product labeling
can be found at www.kyprolis.com or contact Amgen Medical Information at 1-800-772-6436.
This Brief Summary is based on the Kyprolis Prescribing Information v15, 05/17.
U.S. Patent Numbers: http://pat.amgen.com/kyprolis
309195gi501_PI_F_AshDailyNews
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Table of Contents for the Digital Edition of ASH News Daily 2017 - Issue 3
ASH News Daily 2017 - Issue 3 - A-1
ASH News Daily 2017 - Issue 3 - A-2
ASH News Daily 2017 - Issue 3 - A-3
ASH News Daily 2017 - Issue 3 - A-4
ASH News Daily 2017 - Issue 3 - A-5
ASH News Daily 2017 - Issue 3 - A-6
ASH News Daily 2017 - Issue 3 - A-7
ASH News Daily 2017 - Issue 3 - A-8
ASH News Daily 2017 - Issue 3 - A-9
ASH News Daily 2017 - Issue 3 - A-10
ASH News Daily 2017 - Issue 3 - A-11
ASH News Daily 2017 - Issue 3 - A-12
ASH News Daily 2017 - Issue 3 - A-13
ASH News Daily 2017 - Issue 3 - A-14
ASH News Daily 2017 - Issue 3 - A-15
ASH News Daily 2017 - Issue 3 - A-16
ASH News Daily 2017 - Issue 3 - A-17
ASH News Daily 2017 - Issue 3 - A-18
ASH News Daily 2017 - Issue 3 - A-19
ASH News Daily 2017 - Issue 3 - A-20
ASH News Daily 2017 - Issue 3 - A-21
ASH News Daily 2017 - Issue 3 - A-22
ASH News Daily 2017 - Issue 3 - A-23
ASH News Daily 2017 - Issue 3 - A-24
ASH News Daily 2017 - Issue 3 - A-25
ASH News Daily 2017 - Issue 3 - A-26
ASH News Daily 2017 - Issue 3 - A-27
ASH News Daily 2017 - Issue 3 - A-28
ASH News Daily 2017 - Issue 3 - B-1
ASH News Daily 2017 - Issue 3 - B-2
ASH News Daily 2017 - Issue 3 - B-3
ASH News Daily 2017 - Issue 3 - B-4
ASH News Daily 2017 - Issue 3 - B-5
ASH News Daily 2017 - Issue 3 - B-6
ASH News Daily 2017 - Issue 3 - B-7
ASH News Daily 2017 - Issue 3 - B-8
ASH News Daily 2017 - Issue 3 - B-9
ASH News Daily 2017 - Issue 3 - B-10
ASH News Daily 2017 - Issue 3 - B-11
ASH News Daily 2017 - Issue 3 - B-12
ASH News Daily 2017 - Issue 3 - B-13
ASH News Daily 2017 - Issue 3 - B-14
ASH News Daily 2017 - Issue 3 - B-15
ASH News Daily 2017 - Issue 3 - B-16
ASH News Daily 2017 - Issue 3 - B-17
ASH News Daily 2017 - Issue 3 - B-18
ASH News Daily 2017 - Issue 3 - B-19
ASH News Daily 2017 - Issue 3 - B-20
ASH News Daily 2017 - Issue 3 - B-21
ASH News Daily 2017 - Issue 3 - B-22
ASH News Daily 2017 - Issue 3 - B-23
ASH News Daily 2017 - Issue 3 - B-24
ASH News Daily 2017 - Issue 3 - B-25
ASH News Daily 2017 - Issue 3 - B-26
ASH News Daily 2017 - Issue 3 - B-27
ASH News Daily 2017 - Issue 3 - B-30
ASH News Daily 2017 - Issue 3 - B-31
ASH News Daily 2017 - Issue 3 - B-32
ASH News Daily 2017 - Issue 3 - B-33
ASH News Daily 2017 - Issue 3 - B-34
ASH News Daily 2017 - Issue 3 - B-35
ASH News Daily 2017 - Issue 3 - B-36
ASH News Daily 2017 - Issue 3 - B-37
ASH News Daily 2017 - Issue 3 - B-38
ASH News Daily 2017 - Issue 3 - B-39
ASH News Daily 2017 - Issue 3 - B-40
ASH News Daily 2017 - Issue 3 - B-41
ASH News Daily 2017 - Issue 3 - B-42
ASH News Daily 2017 - Issue 3 - B-43
ASH News Daily 2017 - Issue 3 - B-44
ASH News Daily 2017 - Issue 3 - B-45
ASH News Daily 2017 - Issue 3 - B-46
ASH News Daily 2017 - Issue 3 - B-47
ASH News Daily 2017 - Issue 3 - B-48
ASH News Daily 2017 - Issue 3 - B-49
ASH News Daily 2017 - Issue 3 - B-50
ASH News Daily 2017 - Issue 3 - B-51
ASH News Daily 2017 - Issue 3 - B-52
ASH News Daily 2017 - Issue 3 - B-53
ASH News Daily 2017 - Issue 3 - B-54
ASH News Daily 2017 - Issue 3 - B-55
ASH News Daily 2017 - Issue 3 - B-56
ASH News Daily 2017 - Issue 3 - C-1
ASH News Daily 2017 - Issue 3 - C-2
ASH News Daily 2017 - Issue 3 - C-3
ASH News Daily 2017 - Issue 3 - C-4
ASH News Daily 2017 - Issue 3 - C-5
ASH News Daily 2017 - Issue 3 - C-6
ASH News Daily 2017 - Issue 3 - C-7
ASH News Daily 2017 - Issue 3 - C-8
ASH News Daily 2017 - Issue 3 - C-9
ASH News Daily 2017 - Issue 3 - C-10
ASH News Daily 2017 - Issue 3 - C-11
ASH News Daily 2017 - Issue 3 - C-12
ASH News Daily 2017 - Issue 3 - C-13
ASH News Daily 2017 - Issue 3 - C-14
ASH News Daily 2017 - Issue 3 - C-15
ASH News Daily 2017 - Issue 3 - C-16
ASH News Daily 2017 - Issue 3 - C-17
ASH News Daily 2017 - Issue 3 - C-18
ASH News Daily 2017 - Issue 3 - C-19
ASH News Daily 2017 - Issue 3 - C-20
ASH News Daily 2017 - Issue 3 - C-21
ASH News Daily 2017 - Issue 3 - C-22
ASH News Daily 2017 - Issue 3 - C-23
ASH News Daily 2017 - Issue 3 - C-24
ASH News Daily 2017 - Issue 3 - C-25
ASH News Daily 2017 - Issue 3 - C-26
ASH News Daily 2017 - Issue 3 - C-27
ASH News Daily 2017 - Issue 3 - C-28
ASH News Daily 2017 - Issue 3 - C-29
ASH News Daily 2017 - Issue 3 - C-30
ASH News Daily 2017 - Issue 3 - C-31
ASH News Daily 2017 - Issue 3 - C-32
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