CLINICAL NEWS five-year EFS when treated with lymphoiddirected therapy ( 65 ± 12 %), compared with myeloid-directed therapy ( 14 ± 13 %; p values not reported ); however , patients with this subtype fared worse with these treatments than those with single-population ALAL ( 84 ± 4.2 % with lymphoid-directed vs . 43 ± 8.9 % with myeloid-directed therapy ).
“ The spectrum of underlying genetic aberrations is wide [ in ALAL ],” the researchers noted , and the presence of these mutations did not appear to correlate with prognosis . In 202 patients without typical leukemia-associated mutations ( including ETV6 / RUNX1 , TCF3 / PBX1 , RUNX1 / RUNX1T1 , PML / RARA , or CBFB / MYH11 ), outcomes were similar , except among patients with CD19-positive disease .
In this group , five-year EFS was strongly correlated with treatment type : 83 ± 5.3 % for ALL-type treatment versus 0 % for AML-type treatment and 28 ± 14 % for combined therapy ( p < 0.0001 for both ). “ The striking failure of
“[ In our study ], myeloid type of primary treatment correlated with dismal outcomes in [ children with ] CD19-positive leukemias .”
— ONDREJ HRUSAK , MD , PhD myPKFiT for ADVATE Indications for Use
The myPKFiT software is intended for use by licensed healthcare professionals ( HCPs ) who are familiar with hemophilia care . The myPKFiT software can be used to generate ADVATE dosage amount and frequency recommendations for routine prophylaxis for an individual patient 16 years of age and older and body weight of 45 kg or greater , using that patient ’ s age and body weight information and local laboratory FVIII one-stage clotting activity measurements of sparse samples collected from that patient .
A minimum of two sparse sampling points are required at the recommended 3-4 hours (± 30 minutes ) and at 24-32 hours (± 1 hour ) post-infusion . HCPs will also be able to evaluate various prophylaxis dose regimens tailored to an individual patient ’ s needs and treatment plan .
The software output may be used to guide decisions on appropriate ADVATE dose and infusion intervals to maintain FVIII activity levels at or above a user specified minimum FVIII activity level between 1 % to 3 % above natural baseline for an individual patient in accordance with the FDA-approved dosing recommendations provided in the ADVATE Prescribing Information ( PI ).
myPKFiT should only be used to evaluate prophylactic dosing regimens for hemophilia A patients treated with ADVATE , as per the ADVATE PI .
myPKFiT for ADVATE is not indicated for the treatment of von Willebrand disease . myPKFiT for ADVATE should not be used for patients who have developed neutralizing antibody ( inhibitor ) to FVIII products .
myPKFiT for ADVATE is Rx Only . For safe and proper use of the myPKFiT software , please refer to the complete instructions for use in the User Manual .
ADVATE INDICATIONS ADVATE is a recombinant antihemophilic factor indicated for use in children and adults with hemophilia A ( congenital factor VIII deficiency ) for :
• Control and prevention of bleeding episodes .
• Perioperative management .
• Routine prophylaxis to prevent or reduce the frequency of bleeding episodes .
ADVATE is not indicated for the treatment of von Willebrand disease . ADVATE DETAILED IMPORTANT RISK INFORMATION
CONTRAINDICATIONS Patients who have life-threatening hypersensitivity reactions , including anaphylaxis , to mouse or hamster protein or other constituents of the product .
WARNINGS & PRECAUTIONS Hypersensitivity Reactions Allergic-type hypersensitivity reactions , including anaphylaxis , have been reported with ADVATE . Symptoms include dizziness , paresthesia , rash , flushing , facial swelling , urticaria , dyspnea , pruritus , and vomiting . Discontinue ADVATE if hypersensitivity symptoms occur and administer appropriate emergency treatment .
Neutralizing Antibodies Neutralizing antibodies ( inhibitors ) have been reported following administration of ADVATE predominantly in previously untreated patients ( PUPs ) and previously minimally treated patients ( MTPs ). Monitor all patients for the development of factor VIII inhibitors by appropriate clinical observation and laboratory testing . 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 .
ADVERSE REACTIONS
• Serious adverse reactions seen with ADVATE are hypersensitivity reactions , including anaphylaxis , and the development of high-titer inhibitors necessitating alternative treatments to factor VIII .
• The most common adverse reactions observed in clinical trials (> 5 % of subjects ) were pyrexia , headache , cough , nasopharyngitis , arthralgia , vomiting , upper respiratory tract infection , limb injury , nasal congestion , and diarrhea .
Please see ADVATE Brief Summary of Full Prescribing Information on the following page .
Learn more at www . myPKFiT . com
References : 1 . myPKFiT for ADVATE User Manual . Version 2.0 . Bannockburn , IL : Baxalta Incorporated ; 2017 . 2 . Björkman S . Limited blood sampling for pharmacokinetic dose tailoring of FVIII in the prophylactic treatment of haemophilia A . Haemophilia . 2010 ; 16:597-605 . 3 . Álvarez-Román MT , Fernandez-Bello I , de la Corte-Rodríguez H , et al . Experience of tailoring prophylaxis using factor VIII pharmacokinetic parameters estimated with myPKFiT ® in patients with severe haemophilia A without inhibitors . Haemophilia . 2017 ; 23 : e50-e54 .
4 . Lee M , Morfini M , Schulman S , Ingerslev J ; and Factor VIII / Factor IX Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis . The designand analysis of pharmacokinetic studies of coagulation factors . International Society on Thrombosis and Haemostasis . https :// c . ymcdn . com / sites / www . isth . org / resource / groupd4a6f49a-f4ec-450f-9e0f-7be9f0c2ab2e / official _ communicationsfviiipharmaco . pdf . March 21 , 2001 . Accessed February 9 , 2018 .
© 2018 Shire US Inc ., 300 Shire Way , Lexington , MA 02421 . 1-800-828-2088 . All rights reserved . SHIRE and the Shire Logo are registered trademarks of Shire Pharmaceutical Holdings Ireland Limited or its affiliates . ADVATE and MYPKFIT and Logo are trademarks or registered trademarks of Baxalta Incorporated , a wholly owned , indirect subsidiary of Shire plc . S38704 03 / 18