ASH Clinical News ACN_4.1_FULL_ISSUE_DIGITAL | Page 62

On Location ASH Annual Meeting

No Survival Benefit With Adding Rituximab to Ibrutinib in Patients With Chronic Lymphocytic Leukemia

In a randomized , open-label , singlecenter , phase II study , researchers found that the addition of rituximab to ibrutinib did not improve progression-free survival ( PFS ; primary endpoint ) in patients with relapsed and high-risk chronic lymphocytic leukemia ( CLL ), compared with single-agent ibrutinib . However , the combination did lead to more rapid remissions and lower levels of minimal residual disease ( MRD ), according to lead author Jan A . Burger , MD , PhD , of the Department of Leukemia at the MD Anderson Cancer Center in Houston , Texas , who presented the findings at the 2017 ASH Annual Meeting .
“ At this time , single-agent ibrutinib remains the standard of care ,” Dr . Burger said during his presentation .
The study included 206 patients ( median age = 65 years ; range not provided ) with relapsed CLL or treatment-naïve high-risk disease , including 27 ( 37 %) with del17p or TP53 mutations . Patients were randomized to receive ibrutinib 420 mg daily alone ( n = 102 ) or in combination with rituximab 375 mg / m 2 weekly during cycle one , then monthly for cycles two through six ( n = 104 ). Ibrutinib was administered until the development of adverse events ( AEs ), disease progression , or death .
Most patients ( 70 %) were male , 72 percent had unmutated immunoglobulin heavy-chain variable , and 38 percent had advanced stage disease ( defined as Rai stage 3-4 ).
After a median observation time of 25.2 months in the ibrutinib monotherapy arm and 22.7 months in the combination cohort ( ranges not provided ), 79 ( 77 %) and 71 ( 68 %) patients , respectively , were still receiving treatment .
A total of 188 patients were evaluable for response , and the overall response rates ( ORRs ) were 98 percent in the single-agent group and 100 percent in the combination group . There were no significant differences in complete remission ( CR ) or partial remission ( PR ):
• CR : 20 patients ( 21 %) in the single-agent group vs . 26 ( 28 %) in the rituximab / ibrutinib group ( p = 0.309 )
• PR : 72 ( 77 %) vs . 68 ( 72 %; p value not reported )
While patients in the rituximab / ibrutinib cohort appeared to reach CR faster than patients in the single-agent
60 ASH Clinical News
group ( 11.5 vs . 21.1 months ; p = 0.032 ), two-year PFS rates did not significantly differ between the ibrutinib-only and rituximab / ibrutinib cohorts ( 91.2 % vs . 90.4 %; p = 0.788 ).
There also were no differences in survival by del17p status . Bone marrow flow cytometry assessments conducted at the time of last follow-up showed a significantly lower level of residual CLL cells in the ibrutinib / rituximab cohort ( median = 4.9 % CLL
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 , cells ; range not provided ), compared with the ibrutinib group ( median = 17.1 % CLL cells ; range not provided ; p = 0.002 ).
Five patients in the combination cohort and one in the monotherapy cohort experienced CR with MRD-negativity . The
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

Everyone has a distinct profile

Consider your patient . Consider BOSULIF ® .

( 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
Print-only content
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