PHARMACY FORUM Obinutuzumab (Gazyva®) BY J. ANDREW SKIRVIN, PHARMD, BCOP, & RANDI KOwalcZYK, PHARMD What is obinutuzumab? Obinutuzumab is a humanized anti-CD20 monoclonal antibody. J. ANDREW SKIRVIN, PHARMD, BCOP, is How does obinutuzumab work? Associate Clinical Professor, The CD20 antigen is expressed on the surface of pre B- and mature Northeastern University, School of B-lymphocytes. Obinutuzumab binds to a specific epitope of the CD20 mol- Pharmacy, Boston, and RANDI ecule found on B cells. This activates complement-dependent cytotoxicity, an- KOWALCZYK, PHARMD, is at tibody dependent cellular cytoxicity and phagocytosis, all leading to cell death. Northeastern University, School of Pharmacy, Boston. What is this approved for? Obinutuzumab is approved in combination with chlorambucil for FL: urinary tract infection (3%), upper respiratory tract infection treatment of chronic lymphocytic leukemia (CLL). It is also approved (2%), pyrexia (1%), asthenia (1%), sinusitis (1%), and pain in extrem- in combination with bendamustine followed by continued monother- ity (1%). apy for patients with follicular lymphoma (FL) who relapsed after, or are refractory to a rituximab containing regimen. Are there any important drug interactions I should be aware of? What is the basis for this approval? No specific drug interactions have been identified with obintuzumab. Obinutuzumab was approved based on an improvement in progres- sion-free survival (PFS) in a randomized, open-label, multicenter trial How do I adjust the dose in in patients with indolent NHL. The trial compared 396 patients with the setting of renal or hepatic indolent NHL who were randomized to obinutuzumab plus benda- insufficiency? mustine for 6 cycles followed by continued obinutuzumab monother- Based on population pharmacokinetic analysis, a baseline cre- apy for up to 2 years versus 6 cycles of bendamustine. The independent atinine clearance (CrCl) > 30 mL/min does not affect the phar- review median PFS was 14.9 months in the bendamustine arm while macokinetics of obintuzumab. (CrCl < 30 mL/min have not been the median PFS was not reached in the obinutuzumab plus bendamus- studied.) Obintuzumab has not been studied in patients with tine arm (HR 0.55, 95% CI 0.4–0.74; p = 0.00011). The investigator hepatic impairment, currently no recommendations for dose assessed median PFS was 14 months for bendamustine and 29 months adjustment. for obinutuzumab plus bendamustine (HR 0.52, 95% CI 0.39–0.70; p < 0.0001) (J Clin Oncol 2015;33:18_suppl, LBA8502-LBA8502). Practical tips Hepatitis B virus (HBV) reactivation can occur and is associated with How do you administer this drug? a risk of fulminant hepatitis, hepatic failure, and death. Pretreatment Administer as an IV infusion. screening for HBV infection is recommended. • The dosing for CLL is: º Obinutuzumab 100 mg on day 1, 900 mg on day 2, 1,000 mg on What should my patients know about day 8 and 15 of cycle 1 obinutuzumab? º Obintuzumab 1,000 mg on day 1 every 28 days for cycles 2-6 Patients should seek medical attention for: • Symptoms of infusion reactions such as dizziness, nausea, chills, • The dosing for FL is: fever, vomiting, diarrhea, breathing problems, or chest pain. º Obintuzumab 1,000 mg on day 1, 8, and 15 of cycle 1 • Symptoms of TLS such as nausea, vomiting, diarrhea, and º Obintuzumab 1,000 mg on day 1 every 28 days for cycles 2-6, then lethargy º Obintuzumab 1,000 mg every 2 months for 2 years (monotherapy) • Symptoms of infection including fever and cough. • Changes in neurological function such as confusion, dizziness or Are there any premedications needed? loss of balance, difficulty talking or walking, or vision problems To reduce risk of infusion reactions, premedicate patients with IV dexamethasone or methylprednisolone at least 1 hr prior to infusion, What else should I know about 650-1000 mg acetaminophen and an antihistamine (such as 50 mg di- obinutuzumab? phenhydramine) at least 30 minutes prior to obinutuzumab infusion. Advise patients of the need for: Patients who are at high risk of tumor lysis syndrome (TLS) should • Periodic monitoring of blood counts receive prophylaxis with allopurinol and adequate hydration along • Avoid vaccinations with live viral vaccines with monitoring of electrolytes and renal function. • Patients with a history of HBV infection should potentially be considered for prophylaxis of reactivation What are the common side effects associated with obinutuzumab (> or = 10%)? What useful links are available regarding CLL: infusion reactions, neutropenia, thrombocytopenia, anemia, py- obinutuzumab? rexia, cough, nausea, and diarrhea. • www.gazyva.com FL: infusion reactions, neutropenia, nausea, fatigue, cough, diar- • https://www.fda.gov/drugs/informationondrugs/approveddrugs/ rhea, constipation, pyrexia, thrombocytopenia, vomiting, upper respi- ucm488013.htm ratory tract infection, decreased appetite, arthralgia, sinusitis, anemia, asthenia, and urinary tract infection. Any ongoing clinical trials related to obinutuzumab? What are the uncommon side effects Clinical trials involving obinutuzumab are being conducted in several associated with obinutuzumab (less than 10%)? settings including combinations of obinutuzumab and lenadidomide CLL: anemia (4%), leukopenia (4%), diarrhea (2%), urinary tract infec- in CLL and FL, and obintuzumab and ibrutinib in CLL. More infor- tion (1%), pyrexia (<1%), cough (<1%), and nasopharyngitis (<1%). mation can be found online at https://clinicaltrials.gov. OT oncology-times.com Oncology Times 21.