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On Location ASH Annual Meeting

myeloid malignancies and that have been established as risk factors for CVD .

“ During the full duration of follow-up , roughly 10 percent of these patients died from CVD or CVA ,” Dr . Molenaar said ( see TABLE 1 ). Compared with mortality rates in the general population , calculated using data from the Centers for Disease Control ’ s Wonder dataset , “ the risk of having CVD – related mortality is about five or six times higher in a patient with MDS , CMML , or MDS / MPN-unclassifiable ” Dr . Molenaar said . However , the risks among patients with breast or prostate cancer decreased during the 10 years after diagnosis . Relative risks ( RRs ) for CVD – and CVA – related mortality ( adjusted for age , sex , and year ) were :

• CMML : RR = 2.98 ( 95 % CI 2.69- 3.29 ; p = 0.6x10 -90 )

• MDS : RR = 2.61 ( 95 % CI 2.53-2.70 ; p < 1x10 -100 )

• breast cancer : RR = 0.99 ( 0.98-1.00 ; p = 0.03 )

• prostate cancer : RR = 0.90 ( 95 % CI 0.90-0.91 ; p < 1x10 -100 )

Although the risks for CVD – and CVA – related mortality were highest during the first year after cancer diagnosis for patients with CMML and MDS , Dr . Molenaar noted , it remained elevated at two to three times the adjusted risk relative to the general population through 10 years after cancer diagnosis .

This evidence supports the conclusions of prospective case-control studies and the need for screening patients with newly diagnosed CMML and MDS for CVD , the authors concluded .

“ When a patient is diagnosed , [ they should undergo ] a cardiovascular work-up to see if anything can be managed ,” Dr . Molenaar said . “ Our data suggest that those patients can benefit from aggressive cardiovascular risk factor management .”

Though this was a large , populationlevel analysis , he added , it was limited by the lack of “ granular ” data captured in the SEER database . Future analyses are evaluating smaller European registries that capture these data and will hopefully shed more light on the specific types of fatal cardiovascular events , he added .

The authors report no relevant conflicts of interest .

REFERENCE

Molenaar RJ , Radivoyevitch T , Sekeres MA , et al . High rates of atherosclerotic disease-related mortality in myelodysplastic syndromes and chronic myelomonocytic leukemia patients associated with TET2-mutations . Abstract # 421 . Presented at the 2017 American Society of Hematology Annual Meeting , December 10 , 2017 ; Atlanta , GA .

52 ASH Clinical News

TABLE 1 . Rates of Cardiovascular Disease – and Cerebrovascular Accident – Related Mortality

CMML = chronic myelomonocytic leukemia ; MDS = myelodysplastic syndromes

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 2 days , and median number of episodes per patient was 3 ( range 1-268 ). 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 . The median time to onset of increased ALT and AST was 35 and 33 days , respectively , and the median duration for each was 21 days . Perform hepatic enzyme tests at least monthly for the first 3 months and as clinically indicated . In patients with transaminase elevations ,

BOSULIF ® ( bosutinib ) 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

( bosutinib )

Bosutinib ( BOSULIF ®) is recommended by the NCCN ( National Comprehensive Cancer Network ®) 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

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Study design : BOSULIF 500 mg once daily was studied in a Phase 1 / 2 , open-label , multicenter clinical trial ( N = 546 ) in patients with CP CML in second line ( after imatinib ) ( n = 284 ) and in third line ( after imatinib followed by dasatinib or nilotinib ) ( n = 119 ); also in patients with AP ( n = 79 ) or BP ( n = 64 ) CML . The long-term analysis was based on a minimum of 60 months of follow-up for patients with CP CML treated with one prior TKI ( imatinib ) and a minimum of 48 months of follow-up for patients with CP CML treated with imatinib and at least one additional TKI .

AP = accelerated phase ; BP = blast phase ; CP = chronic phase ; TKI = tyrosine kinase inhibitor .

monitor liver enzymes more frequently . One case consistent with drug-induced liver injury occurred in a trial of BOSULIF in combination with letrozole . 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 for renal dysfunction . 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 . In the clinical trial , Grade 3 / 4 fluid retention was reported in 26 patients ( 5 %). Monitor and manage patients using standards of care . Interrupt , dose reduce , or discontinue BOSULIF as necessary .

Embryofetal Toxicity : BOSULIF can cause fetal harm when administered to a pregnant woman . Women of childbearing potential should be advised of