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For Rituximab-Refractory NHL Patients , Adding Obinutuzumab to Bendamustine Improves Progression-Free Survival
Patients with indolent non-Hodgkin lymphoma ( NHL ) who do not respond to regimens containing rituximab have few subsequent treatment options and generally poor outcomes . Research has suggested that adding the monoclonal antibody obinutuzumab to bendamustine ( considered a standard of care for rituximabrefractory NHL patients ) improves outcomes in this patient population .
In the open-label , randomized , multicenter , phase III GADOLIN study , Laurie H . Sehn , MD , of the British Columbia Cancer Agency and the University of British Columbia in Vancouver , Canada , and authors compared the safety and efficacy of induction therapy with obinutuzumab plus bendamustine , followed by obinutuzumab maintenance therapy , with bendamustine alone . The study results , published in The Lancet Oncology , showed that progression-free survival ( PFS ; primary endpoint ) was significantly longer in the combination cohort than in the monotherapy cohort ( not reached vs . 14.9 months ), for a 45 percent lower risk of disease progression ( hazard ratio [ HR ] = 0.55 ; 95 % CI 0.40-0.74 ; p = 0.0001 ).
“ Because all patients in this trial were unresponsive to rituximab or had progressed within six months of receiving it , the improvement in median PFS of more than 15 months with the addition of obinutuzumab is noteworthy ,” the authors wrote , adding that “ the HR is comparable to the benefit previously shown with the addition of rituximab to chemotherapy in rituximab-naive patients .”
In the GADOLIN trial , 396 adult patients were enrolled from 83 sites in 14 countries between April 15 , 2010 , and September 1 , 2014 . Patients were eligible for inclusion if they had :
• histologically documented , CD20-positive indolent NHL ( including follicular lymphoma of grades 1-3a , marginal zone lymphoma , small lymphocytic lymphoma , and Waldenström macroglobulinemia ) that was refractory to rituximab
• at least one bidimensionally measurable lesion (> 1.5 cm in its largest dimension by computed tomography [ CT ] scan )
NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy .
IMPORTANT SAFETY INFORMATION FOR NINLARO
WARNINGS AND PRECAUTIONS
• Thrombocytopenia has been reported with NINLARO . During treatment , monitor platelet counts at least monthly , and consider more frequent monitoring during the first three cycles . Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines . Adjust dosing as needed . Platelet nadirs occurred between Days 14-21 of each 28-day cycle and recovered to baseline by the start of the next cycle .
• Gastrointestinal Toxicities , including diarrhea , constipation , nausea and vomiting , were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications , and supportive care . Diarrhea resulted in the discontinuation of one or more of the three drugs in 1 % of patients in the NINLARO regimen and < 1 % of patients in the placebo regimen . Adjust dosing for severe symptoms .
• an estimated life expectancy of about 5 years
• previously received anti-lymphoma treatment ( including up to four chemotherapy-containing regimens )
Patients were excluded if they had used any monoclonal antibodies other than rituximab in the three months prior to the study , received chemotherapy or other investigational therapy within 28 days prior to the first
EXTEND EFFICACY .
EXTEND THE POSSIBILITIES .
• Peripheral Neuropathy ( predominantly sensory ) was reported with NINLARO . The most commonly reported reaction was peripheral sensory neuropathy ( 19 % and 14 % in the NINLARO and placebo regimens , respectively ). Peripheral motor neuropathy was not commonly reported in either regimen (< 1 %). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1 % of patients in both regimens . Monitor patients for symptoms of peripheral neuropathy and adjust dosing as needed .
• Peripheral Edema was reported with NINLARO . Monitor for fluid retention . Investigate for underlying causes when appropriate and provide supportive care as necessary . Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms .
• Cutaneous Reactions : Rash , most commonly maculopapular and macular rash , was reported with NINLARO . Rash resulted in discontinuation of one or more of the three drugs in < 1 % of patients in both regimens . Manage rash with supportive care or with dose modification .
• Hepatotoxicity has been reported with NINLARO . Drug-induced liver injury , hepatocellular injury , hepatic
44 ASH Clinical News
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