ASH Clinical News July 2017 V2 - Page 20

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 ) 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 .
Written in Blood (4%) received 1.5 mg/kg, eight (16%) received less than the standard therapeu- tic dose, and two (4%) did not have dose information available. A total of 61 cases of ICH (confirmed via radiology reports reviewed by a neuro- oncologist) were recorded in both arms of the study. In addition to the higher risk of major ICH at 1 year, enoxaparin was also associ- ated 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 sig- nificantly 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 time- varying covariate, comparing time on and time off enoxaparin. During ex- posure to enoxaparin, the risk of ma- jor 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 spe- cifically designed to predict ICH with therapeutic anticoagulation in patients with glioma, so the inves- tigators 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 deter- mined 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 cor- responding 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-cen- ter, retrospective design and small patient population. The study was not random- ized, and thus may not have been able to control for all factors determining why some patients received anticoagulation therapy, while others did not. “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] S:6.75” G:.5” 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. 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