Calendar
ASH Consultative Hematology Course
September 7 , 2017 Chicago , IL ( prior to the 2017 ASH Meeting on Hematologic Malignancies )
December 11 , 2017 Atlanta , GA ( during the 2017 ASH Annual Meeting ) An interactive , half-day program in which participants engage in case-based presentations and discussions focusing on non-malignant hematology topics such as thrombosis , thrombocytopenia , and bleeding .
ASH Meeting on Hematologic Malignancies
September 8 – 9 , 2017 Chicago , IL Top experts in hematologic malignancies discuss the latest developments in clinical care and answer challenging patient care questions .
Peer Review Week
September 11 – 17 , 2017 Peer Review Week is an annual global event celebrating the essential role that peer review plays in maintaining scientific quality . The theme “ Transparency in Review ” will be explored in virtual events and in-person discussions that coincide with the Peer Review Congress in Chicago , IL .
Advanced Practice Providers Oncology Summit
The goal of this summit is to foster collaboration , share best practices , and provide a forum for peer-to-peer interaction among advanced practice providers who are actively engaged in caring for oncology patients .
Upcoming Dates and Locations : September 15 – 16 , 2017 Denver , CO
October 13 – 14 , 2017 Portland , OR
7th International Symposium on Acute Promyelocytic Leukemia
September 24 – 27 , 2017 Rome , Italy In addition to advances in biology and treatment of acute promyelocytic leukemia , the meeting includes updates on diagnostics , management , and minimal residual disease assessment .
February 9 – 10 , 2018 Orlando , FL Continued on page 4
RITUXAN HYCELA™ ( rituximab and hyaluronidase human ) injection , for subcutaneous use
Initial U . S . Approval : 2017
This is a brief summary of information about RITUXAN HYCELA . Before prescribing , please see the full Prescribing Information .
WARNING : SEVERE MUCOCUTANEOUS REACTIONS , HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
Severe Mucocutaneous Reactions Severe , including fatal , mucocutaneous reactions can occur in patients receiving rituximab-containing products , including RITUXAN HYCELA [ see Warnings and Precautions ( 5.1 )].
Hepatitis B Virus ( HBV ) Reactivation HBV reactivation can occur in patients treated with rituximab-containing products , including RITUXAN HYCELA , in some cases resulting in fulminant hepatitis , hepatic failure , and death . Screen all patients for HBV infection before treatment initiation , and monitor patients during and after treatment with RITUXAN HYCELA . Discontinue RITUXAN HYCELA and concomitant medications in the event of HBV reactivation [ see Warnings and Precautions ( 5.2 )].
Progressive Multifocal Leukoencephalopathy ( PML ), including fatal PML , can occur in patients receiving rituximab-containing products , including RITUXAN HYCELA [ see Warnings and Precautions ( 5.3 ) and Adverse Reactions ( 6.1 )].
INDICATIONS AND USAGE
1.1 Follicular Lymphoma ( FL ) RITUXAN HYCELA is indicated for the treatment of adult patients with :
• Relapsed or refractory , follicular lymphoma as a single agent .
• Previously untreated follicular lymphoma in combination with first line chemotherapy and , in patients achieving a complete or partial response to rituximab in combination with chemotherapy , as single-agent maintenance therapy .
• Non-progressing ( including stable disease ), follicular lymphoma as a single agent after first-line cyclophosphamide , vincristine , and prednisone ( CVP ) chemotherapy .
1.2 Diffuse Large B-Cell Lymphoma ( DLBCL ) RITUXAN HYCELA is indicated for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma in combination with cyclophosphamide , doxorubicin , vincristine , prednisone ( CHOP ) or other anthracycline-based chemotherapy regimens .
1.3 Chronic Lymphocytic Leukemia ( CLL ) RITUXAN HYCELA is indicated , in combination with fludarabine and cyclophosphamide ( FC ), for the treatment of adult patients with previously untreated and previously treated CLL .
1.4 Limitations of Use
• Initiate treatment with RITUXAN HYCELA only after patients have received at least one full dose of a rituximab product by intravenous infusion [ see Dosage and Administration ( 2.1 ) and Warnings and Precautions ( 5.4 )].
• RITUXAN HYCELA is not indicated for the treatment of non-malignant conditions .
4 CONTRAINDICATIONS None
5 WARNINGS AND PRECAUTIONS
5.1 Severe Mucocutaneous Reactions Mucocutaneous reactions , some with fatal outcome , can occur in patients treated with rituximabcontaining products , including RITUXAN HYCELA . These reactions include paraneoplastic pemphigus , Stevens-Johnson syndrome , lichenoid dermatitis , vesiculobullous dermatitis , and toxic epidermal necrolysis . Discontinue RITUXAN HYCELA in patients who experience a severe mucocutaneous reaction . The safety of re-administration of a rituximab-containing product , including RITUXAN HYCELA , to patients with severe mucocutaneous reactions has not been determined .
5.2 Hepatitis B Virus Reactivation Hepatitis B virus ( HBV ) reactivation , in some cases resulting in fulminant hepatitis , hepatic failure and death , can occur in patients treated with drugs classified as CD20-directed cytolytic antibodies , including rituximab-containing products . HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA levels or detection of HBsAg in a person who was previously HBsAg negative and anti-HBc positive . Reactivation of HBV replication is often followed by hepatitis , i . e ., increase in transaminase levels . In severe cases increase in bilirubin levels , liver failure , and death can occur . Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with a rituximab-containing product . For patients who show evidence of prior hepatitis B infection ( HBsAg positive [ regardless of antibody status ] or HBsAg negative but anti-HBc positive ), consult with physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy before and / or during treatment with a rituximab-containing product . Monitor patients with evidence of current or prior HBV infection for clinical and laboratory signs of hepatitis or HBV reactivation during and for several months following RITUXAN HYCELA . HBV reactivation has been reported up to 24 months following completion of therapy containing rituximab . In patients who develop reactivation of HBV while on RITUXAN HYCELA , immediately discontinue treatment and any concomitant chemotherapy , and institute appropriate treatment . Insufficient data exist regarding the safety of resuming RITUXAN HYCELA treatment in patients who develop HBV reactivation . Resumption of RITUXAN HYCELA treatment in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing HBV .
5.3 Progressive Multifocal Leukoencephalopathy ( PML ) JC virus infection resulting in PML and death has been observed in patients receiving rituximabcontaining products , including RITUXAN HYCELA . Consider the diagnosis of PML in any patient presenting with new-onset neurologic manifestations . Evaluation of PML includes , but is not limited to , consultation with a neurologist , brain MRI , and lumbar puncture . Discontinue RITUXAN HYCELA and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML [ see Adverse Reactions ( 6.1 )].
5.4 Hypersensitivity and other Administration Reactions Systemic Reactions
Patients must receive at least one full dose of a rituximab product by intravenous infusion before receiving RITUXAN HYCELA due to the higher risk of hypersensitivity and other acute reactions during the first infusion [ see Dosage and Administration ( 2.1 )]. Beginning therapy with a rituximab product by intravenous infusion allows management of hypersensitivity and other administration reactions by slowing or stopping the intravenous infusion . Rituximab-containing products , including RITUXAN HYCELA , are associated with hypersensitivity and other administration reactions , which may be related to release of cytokines and / or other chemical mediators . Cytokine release syndrome may be clinically indistinguishable from acute hypersensitivity reactions . This set of reactions which includes syndrome of cytokine release , tumor lysis syndrome and anaphylactic and hypersensitivity reactions are described below . They are not specifically related to the route of administration of a rituximabcontaining product . Severe infusion-related reactions with fatal outcome have been reported with the use of intravenous formulations of rituximab products , with an onset ranging within 30 minutes to 2 hours after starting the first intravenous infusion . They were characterized by pulmonary events in addition to fever , chills , rigors , hypotension , urticaria , angioedema and other symptoms . Anaphylactic and other hypersensitivity reactions can also occur . In contrast to cytokine release syndrome , true hypersensitivity reactions typically occur within minutes after starting infusion . Severe cytokine release syndrome is characterized by severe dyspnea , often associated by bronchospasm and hypoxia , in addition to fever , chills , rigors , urticaria , and angioedema . This syndrome may be associated with acute respiratory failure and death [ see Warnings and Precautions ( 5.5 )]. Cytokine release syndrome may occur within 1 – 2 hours of initiating the infusion . Patients with a history of pulmonary insufficiency or those with pulmonary tumor infiltration may be at a greater risk of poor outcome . Rituximab product administration should be interrupted immediately and aggressive symptomatic treatment initiated .
During RITUXAN HYCELA administration , the injection should be interrupted immediately when observing signs of a severe reaction and aggressive symptomatic treatment should be initiated . Closely monitor the following patients : those with pre-existing cardiac or pulmonary conditions , those who experienced prior cardiopulmonary adverse reactions , and those with high numbers of circulating malignant cells ( ≥ 25,000 / mm 3 ) [ see Warnings and Precautions ( 5.5 , 5.7 )].
Premedicate patients with an antihistamine and acetaminophen prior to each administration of RITUXAN HYCELA [ see Dosage and Administration ( 2.5 )]. Premedication with glucocorticoids should also be considered . Observe patients for at least 15 minutes following RITUXAN HYCELA . A longer period may be appropriate in patients with an increased risk of hypersensitivity reactions . Local Cutaneous Reactions Local cutaneous reactions , including injection site reactions , have been reported in patients receiving RITUXAN HYCELA . Symptoms included pain , swelling , induration , hemorrhage , erythema , pruritus , and rash [ see Adverse Reactions ( 6.1 )]. Some local cutaneous reactions occurred more than 24 hours after RITUXAN HYCELA administration . The incidence of local cutaneous reactions following administration of RITUXAN HYCELA was 16 %. Reactions were mild or moderate and resolved without any specific treatment . Local cutaneous reactions of any Grade were most common during the first RITUXAN HYCELA cycle ( Cycle 2 ; 5 %) with the incidence decreasing with subsequent injections .
5.5 Tumor Lysis Syndrome ( TLS ) TLS can occur within 12 – 24 hours after administration of a rituximab-containing product , including RITUXAN HYCELA . A high number of circulating malignant cells ( ≥ 25,000 / mm 3 ) or high tumor burden confers a greater risk of TLS . Administer aggressive intravenous hydration and anti-hyperuricemic therapy in patients at high risk for TLS . Correct electrolyte abnormalities , monitor renal function and fluid balance , and administer supportive care , including dialysis as indicated [ see Warnings and Precautions ( 5.8 )].
5.6 Infections Serious , including fatal , bacterial , fungal , and new or reactivated viral infections can occur during and following the completion of therapy with rituximab-containing products , including RITUXAN HYCELA . The incidence of infections with RITUXAN HYCELA vs rituximab was 56 % and 49 % respectively in patients with CLL , and 46 % and 41 % respectively in patients with FL / DLBCL in combination with chemotherapy . Infections have been reported in some patients with prolonged hypogammaglobulinemia ( defined as hypogammaglobulinemia > 11 months after rituximab exposure ). New or reactivated viral infections included cytomegalovirus , herpes simplex virus , parvovirus B19 , varicella zoster virus , West Nile virus , and hepatitis B and C . Discontinue RITUXAN HYCELA for serious infections and institute appropriate anti-infective therapy [ see Adverse Reactions ( 6.1 )].
5.7 Cardiovascular Adverse Reactions Cardiac adverse reactions , including ventricular fibrillation , myocardial infarction , and cardiogenic shock may occur with rituximab-containing products , including RITUXAN HYCELA . Discontinue RITUXAN HYCELA for serious or life threatening cardiac arrhythmias . Perform cardiac monitoring during and after all administrations of RITUXAN HYCELA for patients who develop clinically significant arrhythmias , or who have a history of arrhythmia or angina [ see Adverse Reactions ( 6.1 )].
5.8 Renal Toxicity Severe , including fatal , renal toxicity can occur after administration of rituximab-containing products , including RITUXAN HYCELA . Renal toxicity has occurred in patients who experience tumor lysis syndrome and in patients with administered concomitant cisplatin therapy during clinical trials . The combination of cisplatin and RITUXAN HYCELA is not an approved treatment regimen . Monitor closely for signs of renal failure and discontinue RITUXAN HYCELA in patients with a rising serum creatinine or oliguria [ see Warnings and Precautions ( 5.5 )].
5.9 Bowel Obstruction and Perforation Abdominal pain , bowel obstruction and perforation , in some cases leading to death , can occur in patients receiving rituximab-containing products , including RITUXAN HYCELA , in combination with chemotherapy . In postmarketing reports , the mean time to documented gastrointestinal perforation was 6 ( range 1 – 77 ) days . Evaluate if symptoms of obstruction such as abdominal pain or repeated vomiting occur .