ASH Clinical News July 2017 V2 - Page 28

Literature Scan days over the preceding 84 days). In the pomalidomide cohort, responses were non-significantly associated with: • transfusion dependence ≤4 U RBC/28 days (odds ratio [OR] = 3.1; 95% CI 0.9-11.1; p=0.09) • age ≤65 years old (OR=2.3; 95% CI 0.9-5.5; p=0.07) • type of MPN-associated MF (OR=2.6; 95% CI 0.7-9.5; p=0.14) Meanwhile, responses in the pla- cebo cohort were variably associated with: • transfusion dependence ≤4 U RBC/28 days (OR=8.6; 95% CI 0.9-82.3; p=0.06) • WBC count ≥25x10 9 /L at randomization (OR=4.9; 95% CI 0.8-28.9; p=0.08) • interval from diagnosis to randomization of >2 years (OR=4.9; 95% CI 1.1-21.9; p=0.04) The most common treatment- related adverse events (AEs) were peripheral edema, fatigue, pyrexia, and diarrhea, and peripheral edema and neutropenia were significantly more common in the pomalido- mide group. The most common grade ≥3 AEs were neutropenia, thrombocytopenia, anemia, and pneumonia. Dr. Tefferi and colleagues noted several potential limitations of the study, including the use T:1 S:14 KOGENATE FS (Antihemophilic Factor [Recombinant], Formulated with Sucrose) For Intravenous Use, Lyophilized Powder for Reconstitution with Vial Adapter Initial U.S. Approval: 1993 BRIEF SUMMARY CONSULT PACKAGE INSERT FOR FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE Kogenate ® FS is a recombinant antihemophilic factor indicated for: • On-demand treatment and control of bleeding episodes in adults and children with hemophilia A. • Perioperative management of bleeding in adults and children with hemophilia A. • Routine prophylaxis to reduce the frequency of bleeding episodes in children with hemophilia A and to reduce the risk of joint damage in children without pre-existing joint damage. • Routine prophylaxis to reduce the frequency of bleeding episodes in adults with hemophilia A. Kogenate FS is not indicated for the treatment of von Willebrand disease. 4 CONTRAINDICATIONS Kogenate FS is contraindicated in patients who have life-threatening hypersensitivity reactions, including anaphylaxis to mouse or hamster protein or other constituents of the product (sucrose, glycine, histidine, sodium, calcium chloride, polysorbate 80, imidazole, tri-n-butyl phosphate, and copper). 5 WARNINGS AND PRECAUTIONS 5.1 Hypersensitivity Reactions Hypersensitivity reactions, including anaphylaxis have been reported with Kogenate FS. Reported symptoms included facial swelling, flushing, hives, decrease in blood pressure, nausea, rash, restlessness, shortness of breath, tachycardia, tightness of the chest, tingling, urticaria, and vomiting. Kogenate FS contains trace amounts of mouse immunoglobulin G (MuIgG) and hamster (BHK) proteins [see Description (11)]. Patients treated with this product may develop hypersensitivity to these non-human mammalian proteins. Discontinue Kogenate FS if symptoms occur and seek immediate emergency treatment. 5.2 Neutralizing Antibodies Neutralizing antibodies (inhibitors) have been reported following administration of Kogenate FS, predominantly in previously untreated patients (PUPs) [see Adverse Reactions (6)]. Carefully monitor patients for the development of factor VIII inhibitors, using appropriate clinical observations and laboratory tests. 6 If expected plasma factor VIII activity levels are not attained, or if bleeding is not controlled with an expected dose, perform an assay that measures factor VIII inhibitor concentration [see Warnings and Precautions (5.4)]. 5.3 Cardiovascular Risk Factors Hemophilic patients with cardiovascular risk factors or diseases may be at the same risk to develop cardiovascular events as non-hemophilic patients when clotting has been normalized by treatment with factor VIII. 5.4 Monitoring Laboratory Tests • Monitor plasma factor VIII activity levels by the one-stage clotting assay to confirm the adequate factor VIII levels have been achieved and maintained, when clinically indicated [see Dosage and Administration (2)]. • Monitor for development of factor VIII inhibitors. Perform assay to determine if factor VIII inhibitor is present. If expected factor VIII activity plasma levels are not attained or if bleeding is not controlled with the expected dose of Kogenate FS, use Bethesda Units (BU) to titer inhibitors. If the inhibitor is less than 10 BU per mL, the administration of additional Kogenate FS concentrate may neutralize the inhibitor and may permit an appropriate hemostatic response. If inhibitor titers are above 10 BU per mL, adequate hemostasis may not be achieved. The inhibitor titer may rise following Kogenate FS infusion as a result of an anamnestic response to factor VIII. The on-demand treatment and control of bleeding in such patients requires the use of alternative therapeutic approaches and agents. 6 ADVERSE REACTIONS Serious adverse reactions seen with Kogenate FS are systemic hypersensitivity reactions, including bronchospastic reactions and/or hypotension and anaphylaxis, and the development of high-titer inhibitors necessitating alternative treatments to factor VIII. The most common adverse reactions (≥ 4%) observed in clinical trials were inhibitor formation in previously untreated patients (PUPs) and minimally treated patients (MTPs), skin-related hypersensitivity reactions (e.g., rash, pruritus), infusion site reactions (e.g., inflammation, pain), and central venous access device (CVAD) associated infections. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of another drug and may not reflect the rates observed in clinical practice. Previous