Written in Blood
( 4 %) received 1.5 mg / kg , eight ( 16 %) received less than the standard therapeutic dose , and two ( 4 %) did not have dose information available .
A total of 61 cases of ICH ( confirmed via radiology reports reviewed by a neurooncologist ) were recorded in both arms of the study .
In addition to the higher risk of major ICH at 1 year , enoxaparin was also associated with higher rates of measurable ICH ( defined as ICH with a bleed volume ≥1 mL ), compared with controls : 18.8 percent versus 7.8 percent ( HR = 2.16 ; 95 % CI ; 0.99-4.74 ; p = 0.05 ).
The researchers also noted that the rates of major ICH did not significantly differ when they adjusted for type of glioma , age , hypertension , glioma treatment , and administration of anti-angiogenic agents .
To further evaluate the association between enoxaparin and development of ICH , the investigators considered enoxaparin administration as a timevarying covariate , comparing time on and time off enoxaparin . During exposure to enoxaparin , the risk of major ICH increased 13-fold ( HR = 13.29 ; 95 % CI 3.33-52.85 ; p < 0.0001 ).
Median overall survival ( OS ) was similar in the enoxaparin and control cohorts ( 18.7 months vs . 17.1 months ; p = 0.82 ). However , among all patients who experienced a major ICH , OS was significantly shorter for those taking enoxaparin , compared with controls ( 3.3 months vs . 10.2 months ; p = 0.012 ). This association remained significant after the researchers adjusted for time from glioma diagnosis until hemorrhage , as well as age at diagnosis ( HR = 3.74 ; 95 % CI 1.24-11.30 ; p = 0.02 ). “ The median survival was shortened by nearly 70 percent [ with enoxaparin ],” the authors wrote , adding that this was “ a concerning finding .”
There are no risk scores specifically designed to predict ICH with therapeutic anticoagulation in patients with glioma , so the investigators used the PANWARDS risk score – which was developed to predict ICH with anticoagulation in non-cancer cohorts – to determine potential risk in this population .
With PANWARDS , risk is determined by the following variables :
• platelet count
• albumin
• history of congestive heart failure
• warfarin
• age
• race
• diastolic blood pressure
• history of stroke or transient ischemic attack
18 ASH Clinical News
All major ICHs occurred in those with PANWARDS risk scores of ≥25 ( out of a maximum of 99 points ), with a corresponding sensitivity of 100 percent ( 95 % CI 63-100 ) and specificity of 40 percent ( 95 % CI 25-56 ). The cumulative incidence of major ICH at 1 year was 23 percent ( 95 % CI 9.91-39.41 ) in patients with PANWARDS scores ≥25 , compared with 0 percent for those with lower scores ( p = 0.03 ). “ The PANWARDS prediction score may prove useful to identify those glioma patients at highest risk of suffering from a major intracranial hemorrhage ,” Dr . Zwicker said .
The study is limited by its single-center , retrospective design and small patient population . The study was not randomized , and thus may not have been able to control for all factors determining why some patients received anticoagulation therapy , while others did not .
IMPORTANT SAFETY INFORMATION
Contraindication : History of hypersensitivity to BOSULIF . Reactions have included anaphylaxis . Anaphylactic shock occurred in less than 0.2 % of treated patients in clinical trials .
Gastrointestinal Toxicity : Diarrhea , nausea , vomiting , and abdominal pain can occur . In the clinical trial , median time to onset for diarrhea was 2 days , median duration was 1 day , and median number of episodes per patient was 3 ( range 1-221 ). Monitor and manage patients using standards of care , including antidiarrheals , antiemetics , and / or fluid replacement . Withhold , dose reduce , or discontinue BOSULIF as necessary .
Myelosuppression : Thrombocytopenia , anemia , and neutropenia can occur . Perform complete blood counts weekly for the first month and then monthly or as clinically indicated . Withhold , dose reduce , or discontinue BOSULIF as necessary .
Hepatic Toxicity : Twenty percent of patients experienced an increase in either ALT or AST . Liver enzyme elevation usually occurs early in treatment . Perform
“ Additional studies are needed to confirm the prognostic value of the PAN- WARDS scale and to establish the efficacy of alternative therapeutic approaches in those patients considered at high risk of developing an ICH ,” Dr . Zwicker noted .
REFERENCE
Mantia C , Uhlmann EJ , Puligandla M , et al . Predicting the higher rate of intracranial hemorrhage in glioma patients receiving therapeutic enoxaparin . Blood . 2017 May 3 . [ Epub ahead of print ]
BOSULIF is indicated for the treatment of adult patients with chronic , accelerated , or blast phase Philadelphia chromosome – positive ( Ph +) chronic myelogenous leukemia ( CML ) with resistance or intolerance to prior therapy .
In the treatment of adult patients with Ph + CML with resistance or intolerance to prior therapy
Everyone has a distinct profile
Consider your patient . Consider BOSULIF .
( bosutinib )
Print-only content
Bosutinib ( BOSULIF ®) is recommended by the NCCN Clinical Practice Guidelines in Oncology ( NCCN Guidelines ®) as a treatment option for patients with CML in need of 2nd- or later-line TKI therapy . 1
Study design : BOSULIF 500 mg once-daily treatment was studied in a single-arm , Phase 1 / 2 , open-label , multicenter trial ( N = 546 ) in patients with CP , AP , or BP CML in second line ( after imatinib ) or in third line ( after imatinib followed by dasatinib and / or nilotinib ). Of the 546 patients enrolled , 73 % were imatinib resistant and 27 % were imatinib intolerant . 2
AP = accelerated phase ; BP = blast phase ; CP = chronic phase .
hepatic enzyme tests monthly for the first 3 months and as clinically indicated . In patients with transaminase elevations , monitor liver enzymes more frequently . Drug-induced liver injury has occurred . Withhold , dose reduce , or discontinue BOSULIF as necessary . In patients with mild , moderate , or severe hepatic impairment , the recommended starting dose is 200 mg daily .
Renal Toxicity : An on-treatment decline in estimated glomerular filtration rate has occurred in patients treated with BOSULIF . Monitor renal function at baseline and during therapy , with particular attention to patients with preexisting renal impairment or risk factors . Consider dose adjustment in patients with baseline and treatment emergent renal impairment . The recommended starting doses for patients with severe renal impairment ( CrCL < 30 mL / min ) or moderate renal impairment ( CrCL 30-50 mL / min ) are 300 mg and 400 mg daily , respectively .
Fluid Retention : Fluid retention can occur and may cause pericardial effusion , pleural effusion , pulmonary edema , and / or peripheral edema . Monitor and manage patients using standards of care . Interrupt , dose reduce , or discontinue BOSULIF as necessary .