CLINICAL NEWS
Better Together : IDH Inhibitors Plus Azacitidine in Newly Diagnosed AML
Results from a phase Ib / II study presented at the 23rd Congress of the European Hematology Association suggest that combining an IDH inhibitor ( ivosidenib or enasidenib ) with the hypomethylating agent azacitidine leads to high response rates in older patients with previously untreated acute myeloid leukemia ( AML ).
According to lead author and presenter Courtney D . DiNardo , MD , from the University of Texas MD Anderson Cancer Center in Houston , “ the combination of azacitidine with an oral IDH inhibitor was well tolerated , and randomized studies are ongoing ,” she told ASH Clinical News .
The early-phase trial enrolled adults with mutant IDH-positive , newly diagnosed AML who had an Eastern Cooperative Oncology Group ( ECOG ) Performance Status score of ≤2 and were considered ineligible for intensive chemotherapy .
Dr . DiNardo presented data from the dose-finding and dose-expansion phases of the trial , during which 29 participants received treatment in continuous 28-day cycles . All patients received azacitidine 75 mg / m 2 for a total of seven days plus an IDH inhibitor at one of the following dose levels :
Among the patients receiving ivosidenib ( median age = 76 years ; range = 74-82 years ) and enasidenib ( median age = 68 years ; range = 65-76 years ), 82 percent and 83 percent , respectively , presented with an ECOG score of 1 .
As of March 15 , 2018 ( data cutoff ), 19 patients ( 17 in the ivosidenib arm and 2 in the enasidenib arm ) remained on the trial .
“ Treatment-emergent AEs were generally consistent with what has been shown for IDH inhibitors and azacitidine alone ,” Dr . DiNardo reported .
In the ivosidenib arm , the most common AEs were nausea ( n = 14 ), anemia ( n = 12 ), and thrombocytopenia ( n = 11 ),
FACTOR REPLACEMENT MIRRORS THE PROTECTION WITHIN while the most common grade 3-4 AEs were anemia and thrombocytopenia ( n = 10 each ) and febrile neutropenia ( n = 9 ). In the enasidenib arm , the most common AEs were hyperbilirubinemia ( n = 5 ) and abdominal pain , nausea , vomiting , and pyrexia ( n = 4 each ). The most common grade 3-4 AEs in this arm were anemia and
• once-daily ivosidenib 500 mg ( n = 23 )
• once-daily enasidenib 100 mg ( n = 3 )
• once-daily enasidenib 200 mg ( n = 3 )
[ Further research will determine ] “ whether development of IDH MRDnegative status can be used to predict durable responses .”
— COURTNEY D . DiNARDO , MD
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References : 1 . Franchini M , Mannucci PM . The history of hemophilia . Semin Thromb Hemost . 2014 ; 40:571-576 . 2 . Peyvandi F , Garagiola I , Young G . The past and future of haemophilia : diagnosis , treatments , and its complications . Lancet . 2016 ; 388:187-197 . 3 . Lenting PJ , van Mourik JA , Mertens K . The life cycle of coagulation factor VIII in view of its structure and function . Blood . 1998 ; 92 ( 11 ): 3983-3996 . 4 . Antovic A , Mikovic D , Elezovic I , Zabczyk M , Hutenby K , Antovic JP . Improvement of fibrin clot structure after factor VIII injection in haemophilia A patients treated on demand . Thromb Haemost . 2013 ; 111 ( 4 ): 656-661 . 5 . Hvas AM , Sørensen HT , Norengaard L , Christiansen K , Ingerslev J , Sørensen B . Tranexamic acid combined with recombinant factor VIII increases clot resistance to accelerated fibrinolysis in severe hemophilia A . J Thromb Haemost . 2007 ; 5:2408-2414 .
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