Calendar
ASH Workshop on Genome Editing
July 14 – 15 , 2016 Washington , DC The ASH Workshop on Genome Editing provides a forum that focuses specifically on the mechanistic aspects and possible clinical applications of this technology to blood disorders , as well as a platform for the exchange of ideas among academic researchers , industry scientists , and regulators involved in the clinical application of genomeediting technology .
International Society of Experimental Hematology 45th Annual Scientific Meeting
August 25 – 28 , 2016 San Diego , CA ISEH ’ s annual meeting features presentations on cutting-edge , unpublished hematologic research .
18th Meeting of the European Association for Haematopathology
September 3 – 8 , 2016 Basel , Switzerland The program will offer a well-balanced mixture of scientific and practical issues of the topics to be covered . The meeting will start with the educational session , followed by the Bone Marrow and Lymphoma symposia and workshops . The scientific program will include “ Meet the Professor ” sessions , satellite symposia , and poster presentation and discussion .
Washington , DC
GAZYVA ® ( obinutuzumab ) injection , for intravenous infusion Initial U . S . Approval : 2013
This is a brief summary of information about GAZYVA . Before prescribing , please see full Prescribing Information .
WARNING : HEPATITIS B VIRUS REACTIVATION and PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY
• Hepatitis B Virus ( HBV ) reactivation , in some cases resulting in fulminant hepatitis , hepatic failure , and death , can occur in patients receiving CD20-directed cytolytic antibodies , including GAZYVA . Screen all patients for HBV infection before treatment initiation . Monitor HBV-positive patients during and after treatment with GAZYVA . Discontinue GAZYVA and concomitant medications in the event of HBV reactivation [ see Warnings and Precautions ( 5.1 )].
• Progressive Multifocal Leukoencephalopathy ( PML ) including fatal PML , can occur in patients receiving GAZYVA [ see Warnings and Precautions ( 5.2 )].
1 INDICATIONS AND USAGE 1.1 Chronic Lymphocytic Leukemia GAZYVA , in combination with chlorambucil , is indicated for the treatment of patients with previously untreated chronic lymphocytic leukemia ( CLL ) [ see Clinical Studies ( 14.1 )].
1.2 Follicular Lymphoma GAZYVA , in combination with bendamustine followed by GAZYVA monotherapy , is indicated for the treatment of patients with follicular lymphoma ( FL ) who relapsed after , or are refractory to , a rituximabcontaining regimen [ see Clinical Studies ( 14.2 )].
4 CONTRAINDICATIONS None .
5 WARNINGS AND PRECAUTIONS 5.1 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 anti-CD20 antibodies such as GAZYVA . HBV reactivation has been reported in patients who are hepatitis B surface antigen ( HBsAg ) positive and also in patients who are HBsAg negative but are hepatitis B core antibody ( anti-HBc ) positive . Reactivation has also occurred in patients who appear to have resolved hepatitis B infection ( i . e ., HBsAg negative , anti-HBc positive , and hepatitis B surface antibody [ anti-HBs ] positive ).
HBV reactivation is defined as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level 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 and , in severe cases , increase in bilirubin levels , liver failure , and death .
Screen all patients for HBV infection by measuring HBsAg and anti-HBc before initiating treatment with GAZYVA . For patients who show evidence of hepatitis B infection ( HBsAg positive [ regardless of antibody status ] or HBsAg negative but anti- HBc positive ), consult physicians with expertise in managing hepatitis B regarding monitoring and consideration for HBV antiviral therapy .
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 treatment with GAZYVA . HBV reactivation has been reported for other CD20- directed cytolytic antibodies following completion of therapy .
In patients who develop reactivation of HBV while receiving GAZYVA , immediately discontinue GAZYVA and any concomitant chemotherapy and institute appropriate treatment . Resumption of GAZYVA in patients whose HBV reactivation resolves should be discussed with physicians with expertise in managing hepatitis B . Insufficient data exist regarding the safety of resuming GAZYVA in patients who develop HBV reactivation .
5.2 Progressive Multifocal Leukoencephalopathy JC virus infection resulting in progressive multifocal leukoencephalopathy ( PML ), which can be fatal , was observed in patients treated with GAZYVA . Consider the diagnosis of PML in any patient presenting with new onset or changes to preexisting neurologic manifestations . Evaluation of PML includes , but is not limited to , consultation with a neurologist , brain MRI , and lumbar puncture . Discontinue GAZYVA therapy and consider discontinuation or reduction of any concomitant chemotherapy or immunosuppressive therapy in patients who develop PML .
5.3 Infusion Reactions GAZYVA can cause severe and life-threatening infusion reactions . Sixty-five percent of patients with CLL experienced a reaction to the first 1000 mg infused of GAZYVA . Thirty-eight percent of iNHL patients experienced a reaction on Day 1 of GAZYVA infusion . Infusion reactions can also occur with subsequent infusions . Symptoms may include hypotension , tachycardia , dyspnea , and respiratory symptoms ( e . g ., bronchospasm , larynx and throat irritation , wheezing , laryngeal edema ). Most frequently reported symptoms include nausea , fatigue , dizziness , vomiting , diarrhea , hypertension , flushing , headache , pyrexia , and chills [ see Adverse Reactions ( 6.1 )].
Premedicate patients with acetaminophen , antihistamine , and a glucocorticoid . Institute medical management ( e . g ., glucocorticoids , epinephrine , bronchodilators , and / or oxygen ) for infusion reactions as needed . Closely monitor patients during the entire infusion . Infusion reactions within 24 hours of receiving GAZYVA have occurred [ see Dosage and Administration ( 2 )].
For patients with any Grade 4 infusion reactions , including but not limited to anaphylaxis , acute life-threatening respiratory symptoms , or other life-threatening infusion reaction : Stop the GAZYVA infusion . Permanently discontinue GAZYVA therapy .
For patients with Grade 1 , 2 , or 3 infusion reactions : Interrupt GAZYVA for Grade 3 reactions until resolution of symptoms . Interrupt or reduce the rate of the infusion for Grade 1 or 2 reactions and manage symptoms [ see Dosage and Administration ( 2 )].
For patients with preexisting cardiac or pulmonary conditions , monitor more frequently throughout the infusion and the post-infusion period since they may be at greater risk of experiencing more severe reactions . Hypotension may occur as part of the GAZYVA infusion reaction . Consider withholding antihypertensive treatments for 12 hours prior to , during each GAZYVA infusion , and for the first hour after administration until blood pressure is stable . For patients at increased risk of hypertensive crisis , consider the benefits versus the risks of withholding their antihypertensive medication as is suggested here .
5.4 Tumor Lysis Syndrome Tumor Lysis Syndrome ( TLS ), including fatal cases , has been reported in patients receiving GAZYVA . Patients with high tumor burden , high circulating lymphocyte count (> 25 x 10 9 / L ) or renal impairment are at greater risk for TLS and should receive appropriate tumor lysis prophylaxis with anti-hyperuricemics ( e . g ., allopurinol or rasburicase ) and hydration prior to the infusion of GAZYVA [ see Dosage and Administration ( 2.2 )].
During the initial days of GAZYVA treatment , monitor the laboratory parameters of patients considered at risk for TLS . For treatment of TLS , correct electrolyte abnormalities , monitor renal function and fluid balance , and administer supportive care , including dialysis as indicated .
5.5 Infections Serious bacterial , fungal , and new or reactivated viral infections can occur during and following GAZYVA therapy . Fatal infections have been reported with GAZYVA . Do not administer GAZYVA to patients with an active infection . Patients with a history of recurring or chronic infections may be at increased risk of infection .
5.6 Neutropenia Severe and life threatening neutropenia , including febrile neutropenia , has been reported during treatment with GAZYVA . Patients with Grade 3 to 4 neutropenia should be monitored frequently with regular laboratory tests until resolution . Anticipate , evaluate , and treat any symptoms or signs of developing infection . Consider administration of granulocyte colony-stimulating factors ( G-CSF ) in patients with Grade 3 or 4 neutropenia .
Neutropenia can also be of late onset ( occurring more than 28 days after completion of treatment ) and / or prolonged ( lasting longer than 28 days ).
Consider dose delays in the case of Grade 3 or 4 neutropenia . Patients with severe and long lasting (> 1 week ) neutropenia are strongly recommended to receive antimicrobial prophylaxis until resolution of neutropenia to Grade 1 or 2 . Antiviral and antifungal prophylaxis should be considered .
5.7 Thrombocytopenia Severe and life threatening thrombocytopenia has been reported during treatment with GAZYVA in combination with chlorambucil or bendamustine .
Fatal hemorrhagic events during Cycle 1 have also been reported in patients with CLL treated with GAZYVA . Monitor all patients frequently for thrombocytopenia and hemorrhagic events , especially during the first cycle . In patients with Grade 3 or 4 thrombocytopenia , monitor platelet counts more frequently until resolution and consider subsequent dose delays of GAZYVA and chemotherapy or dose reductions of chemotherapy . Transfusion of blood products ( i . e ., platelet transfusion ) may be necessary . Consider withholding concomitant medications which may increase bleeding risk ( platelet inhibitors , anticoagulants ), especially during the first cycle .
5.8 Immunization The safety and efficacy of immunization with live or attenuated viral vaccines during or following GAZYVA therapy have not been studied . Immunization with live virus vaccines is not recommended during treatment and until B-cell recovery .
6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the label :
• Hepatitis B reactivation [ see Warnings and Precautions ( 5.1 )]
• Progressive multifocal leukoencephalopathy [ see Warnings and Precautions ( 5.2 )]
• Infusion reactions [ see Warnings and Precautions ( 5.3 )]
• Tumor lysis syndrome [ see Warnings and Precautions ( 5.4 )]
• Infections [ see Warnings and Precautions ( 5.5 )]
• Neutropenia [ see Warnings and Precautions ( 5.6 )]
• Thrombocytopenia [ see Warnings and Precautions ( 5.7 )]
6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions , adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice .
Summary of Clinical Trial Experience in Chronic Lymphocytic Leukemia The data described in Tables 4-5 below are based on a safety population of 773 previously untreated patients with CLL . Patients were treated with chlorambucil alone , GAZYVA in combination with chlorambucil , or rituximab in combination with chlorambucil . The Stage 1 analysis compared GAZYVA in combination with chlorambucil vs . chlorambucil alone , and Stage 2 compared GAZYVA in combination with chlorambucil vs . rituximab in combination with chlorambucil . Adverse reactions rates and laboratory abnormalities from the Stage 2 phase are presented below and are consistent with the rates in Stage 1 . In addition to the adverse reactions observed in Stage 2 , in Stage 1 back pain ( 5 % vs . 2 %), anemia ( 12 % vs . 10 %) and cough ( 10 % vs . 7 %) were observed at a higher incidence in the obinutuzumab treated patients . The incidence of Grade 3-4 back pain (< 1 % vs . 0 %), cough ( 0 % vs . < 1 %) and anemia ( 5 % vs . 4 %) was similar in both treatment arms . With regard to laboratory abnormalities , in Stage 1 hyperkalemia ( 33 % vs . 18 %), creatinine increased ( 30 % vs . 20 %) and alkaline phosphatase increased ( 18 % vs . 11 %) were observed at a higher incidence in patients treated with obinutuzumab with similar incidences of Grade 3-4 abnormalities between the two arms .
Patients received three 1000 mg doses of GAZYVA on the first cycle and a single dose of 1000 mg once every 28 days for 5 additional cycles in combination with chlorambucil ( 6 cycles of 28 days each in total ). In the last 140 patients enrolled , the first dose of GAZYVA was split between day 1 ( 100 mg ) and day 2 ( 900 mg ) [ see Dosage and Administration ( 2.1 )]. In total , 81 % of patients received all 6 cycles ( of 28 days each ) of GAZYVA-based therapy .
The most common adverse reactions ( incidence ≥ 10 %) observed in patients with CLL in the GAZYVA containing arm were infusion reactions , neutropenia , thrombocytopenia , anemia , pyrexia , cough , nausea , and diarrhea .
The most common Grade 3-4 adverse reactions ( incidence ≥ 10 %) observed in patients with CLL in the GAZYVA containing arm were neutropenia , infusion reactions , and thrombocytopenia .
Calendar
ASH Workshop on Genome Editing
July 14 – 15, 2016
Washington, DC
The ASH Workshop on Genome Editing provides a forum
that focuses specifically on the mechanistic aspects and
possible clinical applications of this technology to blood
disorders, as well as a platform for the exchange of ideas
among academic researchers, industry scientists, and
regulators involved in the clinical application of genomeediting technology.
International Society of Experimental
Hematology 45th Annual Scientific Meeting
August 25 – 28, 2016
San Diego, CA
ISEH’s annual meeting features presentations on
cutting-edge, unpublished hematologic research.
18th Meeting of the European Association
for Haematopathology
September 3 – 8, 2016
Basel, Switzerland
The program will offer a well-balanced mixture of
scientific and practical issues of the topics to be covered.
The meeting will start with the educational session,
followed by the Bone Marrow and Lymphoma symposia
and workshops. The scientific program will include “Meet
the Professor” sessions, satellite symposia, and poster
presentation and discussion.
Washington, DC
GAZYVA® (obinutuzumab)
injection, for intravenous infusion
Initial U.S. Approval: 2013
This is a brief summary of information about
GAZYVA. Before prescribing, please see full
Prescribing Information.
WARNING: HEPATITIS B VIRUS REACTIVATION
and PROGRESSIVE MULTIFOCAL
LEUKOENCEPHALOPATHY
• Hepatitis B Virus (HBV) reactivation,
in some cases resulting in fulminant
hepatitis, hepatic failure, and death, can
occur in patients receiving CD20-directed
cytolytic antibodies, including GAZYVA.
Screen all patients for HBV infection before
treatment initiation. Monitor HBV-positive
patients during and after treatment with
GAZYVA. Discontinue GAZYVA and
concomitant medications in the event
of HBV reactivation [see Warnings and
Precautions (5.1)].
• Progressive Multifocal
Leukoencephalopathy (PML) including
fatal PML, can occur in patients receiving
GAZYVA [see Warnings and Precautions
(5.2)].
1 INDICATIONS AND USAGE
1.1 Chronic Lymphocytic Leukemia
GAZYVA, in combination with chlorambucil, is
indicated for the treatment of patients with previously
untreated chronic lymphocytic leukemia (CLL) [see
Clinical Studies (14.1)].
1.2 Follicular Lymphoma
GAZYVA, in combination with bendamustine followed
by GAZYVA monotherapy, is indicated for the
treatment of patients with follicular lymphoma (FL)
who relapsed after, or are refractory to, a rituximabcontaining regimen [see Clinical Studies (14.2)].
4 CONTRAINDICATIONS
None.
5 WARNINGS AND PRECAUTIONS
5.1 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 anti-CD20
antibodies such as GAZYVA. HBV reactivation has
been reported in patients who are hepatitis B surface
antigen (HBsAg) positive and also in patients who
are HBsAg negative but are hepatitis B core antibody
(anti-HBc) positive. Reactivation has also occurred
in patients who appear to have resolved hepatitis
B infection (i.e., HBsAg negative, anti-HBc positive,
and hepatitis B surface antibody [anti-HBs] positive).
HBV reactivation is defined as an abrupt increase
in HBV replication manifesting as a rapid increase
in serum HBV DNA level or detection of HBsAg in a
person who was previously HBsAg negative and antiHBc positive. Reactivation of HBV replication is often
followed by hepatitis, i.e., increase in transaminase
levels and, in severe cases, increase in bilirubin levels,
liver failure, and death.
Screen all patients for HBV infection by measuring
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