ASH Clinical News ACN_5.1_Digital - Page 18

LEFT • Immune system disorders: drug hypersensitivity • Infections and infestations: bronchopneumonia, gastroenteritis, influenza, lung infection, nasopharyngitis, pneumonia, rhinitis, sepsis, urinary tract infection, viral infection • Metabolism and nutrition disorders: decreased appetite, dehydration, hypercalcemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, tumor lysis syndrome • Musculoskeletal and connective tissue disorders: muscular weakness, musculoskeletal chest pain, musculoskeletal pain, myalgia • Nervous system disorders: cerebrovascular accident, dizziness, hypoesthesia, paresthesia, posterior reversible encephalopathy syndrome • Psychiatric disorders: anxiety • Renal and urinary disorders: renal failure, renal failure acute, renal impairment • Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome, dysphonia, epistaxis, interstitial lung disease, oropharyngeal pain, pneumonitis pulmonary embolism, pulmonary edema, pulmonary hypertension, wheezing • Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, rash • Vascular disorders: deep vein thrombosis, flushing, hypotension A.R.R.O.W. evaluated patients with relapsed and refractory multiple myeloma. Patients received treatment for a median duration of 38 weeks in the once weekly Kd 20/70 mg/m 2 arm and 29.1 weeks in the twice weekly Kd 20/27 mg/m 2 arm of A.R.R.O.W.. The safety profile for the once weekly Kd 20/70 mg/m 2 regimen was similar to the twice weekly Kd 20/27 mg/m 2 regimen. Deaths due to adverse reactions within 30 days of last study treatment occurred in 22/238 (9%) patients in the Kd 20/70 mg/m 2 arm and 18/235 (8%) patients in the Kd 20/27 mg/m 2 arm. The most frequent fatal adverse reactions occurring in patients (%) in the two arms (once weekly Kd 20/70 mg/m 2 versus twice weekly Kd 20/27 mg/m 2 ) were sepsis 2 (< 1%) versus 2 (< 1%), septic shock 2 (< 1%) versus 1 (< 1%), and infection 2 (< 1%) versus 0 (0%). Serious adverse reactions were reported in 43% of the patients in the Kd 20/70 mg/m 2 arm and 41% of the patients in the Kd 20/27 mg/m 2 arm. In both treatment arms, pneumonia was the most commonly reported serious adverse reaction (8% versus 7%). In patients treated with once weekly Kd 20/70 mg/m 2 , 57% were 65 and over and 19% were 75 and over. The incidence of serious adverse events was 37% in patients < 65 years of age, 50% in patients 65 to 74 years of age, and 44% in patients ≥ 75 years of age. Discontinuation due to any adverse reaction occurred in 13% in the Kd 20/70 mg/m 2 arm versus 12% in the Kd 20/27 mg/m 2 arm. The most common reaction leading to discontinuation was acute kidney injury (2% versus 2%). The incidence of cardiac failure events was 3.8% in the once weekly Kd 20/70 mg/m 2 arm versus 5.1% in the twice weekly Kd 20/27 mg/m 2 arm. Most Common Adverse Reactions (≥ 10% in either Kd Arm) Once weekly Kd 20/70 mg/m 2 (N = 238), n (%) Adverse Reactions by Body System Twice weekly Kd 20/27 mg/m 2 (N = 235), n (%) Any Grade ≥ Grade 3 Any Grade ≥ Grade 3 Anemia a 64 (26.9) 42 (17.6) 76 (32.3) 42 (17.9) Thrombocytopenia b 53 (22.3) 26 (10.9) 41 (17.4) 27 (11.5) Neutropenia c 30 (12.6) 21 (8.8) 27 (11.5) 17 (7.2) Diarrhea 44 (18.5) 2 (0.8) 47 (20.0) 3 (1.3) Nausea 34 (14.3) 1 (0.4) 26 (11.1) 2 (0.9) Blood and Lymphatic System Disorders Gastrointestinal Disorders General Disorders and Administration Site Conditions Pyrexia 55 (23.1) 2 (0.8) 38 (16.2) 4 (1.7) Fatigue 48 (20.2) 11 (4.6) 47 (20.0) 5 (2.1) Asthenia 24 (10.1) 3 (1.3) 25 (10.6) 2 (0.9) Peripheral edema 18 (7.6) 0 (0.0) 25 (10.6) 2 (0.9) Infections and Infestations K • Cardiac disorders: atrial fibrillation, cardiac arrest, cardiac failure, cardiac failure congestive, myocardial infarction, myocardial ischemia, palpitations, pericardial effusion, tachycardia • Ear and labyrinth disorders: tinnitus • Eye disorders: cataract, vision blurred • Gastrointestinal disorders: abdominal pain, abdominal pain upper, constipation, dyspepsia, toothache, vomiting • General disorders and administration site conditions: chest pain, chills, influenza like illness, infusion site reactions (including inflammation, pain, and erythema), malaise, pain • Hepatobiliary disorders: cholestasis, hepatic failure, hyperbilirubinemia • Infections and infestations: clostridium difficile colitis, gastroenteritis, influenza, lung infection, nasopharyngitis, rhinitis, sepsis, septic shock, urinary tract infection, viral infection • Metabolism and nutrition disorders: decreased appetite, dehydration, hypercalcemia, hyperglycemia, hyperkalemia, hyperuricemia, hypoalbuminemia, hypocalcemia, hypomagnesemia, hyponatremia, hypophosphatemia, tumor lysis syndrome • Musculoskeletal and connective tissue disorders: muscle spasms, muscular weakness, musculoskeletal chest pain, musculoskeletal pain, myalgia • Nervous system disorders: cerebrovascular accident, dizziness, paresthesia, peripheral neuropathy • Psychiatric disorders: anxiety, delirium • Renal and urinary disorders: acute kidney injury, renal failure, renal impairment • Respiratory, thoracic and mediastinal disorders: acute respiratory distress syndrome, dysphonia, epistaxis, interstitial lung disease, oropharyngeal pain, pneumonitis pulmonary hemorrhage, pulmonary embolism, pulmonary hypertension, pulmonary edema, wheezing • Skin and subcutaneous tissue disorders: erythema, hyperhidrosis, pruritus, rash • Vascular disorders: deep vein thrombosis, flushing, hypotension 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. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary Kyprolis can cause fetal harm based on findings from animal studies and the drug’s mechanism of action. There are no studies with the use of Kyprolis in pregnant women to inform drug-associated risks of adverse developmental outcomes. Kyprolis caused embryo-fetal lethality in rabbits at doses lower than the clinical dose. Advise pregnant women of the potential risk to the fetus. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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. Lactation Risk Summary There are no data on the presence of Kyprolis in human milk, the effects on the breastfed child, or the effects of the drug on milk production. Because many drugs are excreted in human milk and because the potential for serious adverse reactions in a breastfed child from Kyprolis is unknown, advise nursing women not to breastfeed during treatment with Kyprolis and for 2 weeks after treatment. Females and Males of Reproductive Potential Based on its mechanism of action and findings in animals, Kyprolis can cause fetal harm when administered to a pregnant woman. Pregnancy Testing Conduct pregnancy testing on females of reproductive potential prior to initiating Kyprolis treatment. Contraception Females Advise females of reproductive potential to avoid pregnancy and use effective contraception during treatment with Kyprolis and for at least 6 months following the final dose. Males Advise males with female sexual partners of reproductive potential to use effective contraception during treatment with Kyprolis and for at least 3 months following the final dose. Infertility Based on the mechanism of action, Kyprolis may have an effect on either male or female fertility. There are no data on the effect of Kyprolis on human fertility. Respiratory tract infection d 70 (29.4) 7 (2.9) 79 (33.6) 7 (3.0) Pneumonia 28 (11.8) 24 (10.1) 20 (8.5) 16 (6.8) Bronchitis 27 (11.3) 2 (0.8) 25 (10.6) 5 (2.1) 28 (11.8) 2 (0.8) 28 (11.9) 4 (1.7) Pediatric Use The safety and effectiveness of Kyprolis in pediatric patients have not been established. 25 (10.5) 1 (0.4) 23 (9.8) 1 (0.4) 35 (14.7) 2 (0.8) 47 (20.0) 0 (0.0) Geriatric Use Of 1691 patients in clinical studies of Kyprolis, 50.4% were 65 and over, while 15.4% were 75 and over. The incidence of serious adverse events in patients 65 and over was higher than the incidence in younger patients. No overall differences in effectiveness were observed between older and younger patients. Musculoskeletal and Connective Tissue Disorders Back pain Nervous System Disorders Headache Psychiatric Disorders Insomnia Respiratory, Thoracic and Mediastinal Disorders Cough e 37 (15.5) 2 (0.8) 31 (13.2) 0 (0.0) Dyspnea f 28 (11.8) 1 (0.4) 26 (11.1) 2 (0.9) 51 (21.4) 13 (5.5) 48 (20.4) 12 (5.1) Vascular Disorders Hypertension g Kd = Kyprolis and dexamethasone. a Anemia includes anemia, hematocrit decreased, and hemoglobin decreased. b Thrombocytopenia includes platelet count decreased and thrombocytopenia. c Neutropenia includes neutrophil count decreased and neutropenia. d Respiratory tract infection includes respiratory tract infection, lower respiratory tract infection, upper respiratory tract infection, and viral upper respiratory tract infection. e Cough includes cough and productive cough. f Dyspnea includes dyspnea and dyspnea exertional. g Hypertension includes hypertension and hypertensive crisis. Adverse Reactions Occurring at a Frequency of < 10% • Blood and lymphatic system disorders: febrile neutropenia, leukopenia, lymphopenia, neutropenia, thrombotic microangiopathy Hepatic Impairment Reduce the dose of Kyprolis by 25% in patients with mild (total bilirubin 1 to 1.5 × ULN and any AST or total bilirubin ≤ ULN and AST > ULN) or moderate (total bilirubin > 1.5 to 3 × ULN and any AST) hepatic impairment. Dosing recommendation cannot be made for patients with severe hepatic function. 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%). Overdosage Acute onset of chills, hypotension, renal insufficiency, thrombocytopenia, and lymphopenia has been reported following a dose of 200 mg of Kyprolis administrated in error. There is no known specific antidote for Kyprolis overdosage. In the event of overdose, the patient should be monitored, specifically for the side effects and/or adverse reactions listed. 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 v19, 09/18. U.S. Patent Numbers: http://pat.amgen.com/kyprolis 310408gi401_PI_Kng df Spread: Trim: 20.5"w × 13"h Live: 19"w × 12.5"h (includes gutter .5 each side from center) Page: Trim: 10.25"w × 13"h Live: 9.5"w × 12.5"h Output @ 100% Giant Creative Strategy