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American Society for Radiation Oncology Annual Meeting
September 24 – 27 , 2017 San Diego , CA The 58th ASTRO Annual Meeting creates a forum for global collaboration on issues in radiation oncology .
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American Association of Blood Banks Annual Meeting
October 7 – 10 , 2017 San Diego , CA The AABB Annual Meeting brings together transfusion specialists , laboratory supervisors , cellular therapy and blood banking professionals , medical technologists , donor recruiters , physicians , and nurses to advance transfusion and cellular therapies worldwide .
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CAP17 : The Pathologists ’ Meeting
October 8 – 11 , 2017 National Harbor , MD The College of American Pathologists ’ 2017 meeting brings together pathology and laboratory medicine experts from around the world .
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2017 American Society of Hematology Annual Meeting
December 9 – 12 , 2017 Atlanta , GA The 59th ASH Annual Meeting and Exposition will provide an invaluable educational experience and the opportunity to review thousands of scientific abstracts highlighting updates in the hottest topics in hematology .
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5.10 Immunization The safety of immunization with live viral vaccines following rituximab-containing products , including RITUXAN HYCELA , therapy has not been studied and vaccination with live virus vaccines is not recommended before or during treatment . 5.11 Embryo-Fetal Toxicity Based on human data , rituximab-containing products can cause fetal harm due to B-cell lymphocytopenia in infants exposed to rituximab in-utero . Advise pregnant women of the risk to a fetus . Females of childbearing potential should use effective contraception while receiving RITUXAN HYCELA and for 12 months following the last dose of rituximab-containing products , including RITUXAN HYCELA .
6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling :
• Mucocutaneous reactions [ see Warnings and Precautions ( 5.1 )]
• Hepatitis B reactivation including fulminant hepatitis [ see Warnings and Precautions ( 5.2 )]
• Progressive multifocal leukoencephalopathy [ see Warnings and Precautions ( 5.3 )]
• Hypersensitivity and other administration reactions [ see Warnings and Precautions ( 5.4 )]
• Tumor lysis syndrome [ see Warnings and Precautions ( 5.5 )]
• Infections [ see Warnings and Precautions ( 5.6 )]
• Cardiac arrhythmias [ see Warnings and Precautions ( 5.7 )]
• Renal toxicity [ see Warnings and Precautions ( 5.8 )]
• Bowel obstruction and perforation [ see Warnings and Precautions ( 5.9 )]
6.1 Clinical Trials 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 clinical practice . The data described below reflect exposure to RITUXAN HYCELA in 892 patients in four controlled trials with exposures ranging from a single injection up to 27 months of treatment . The population included 382 patients with follicular lymphoma ( FL ), 369 patients with diffuse large B-cell lymphoma ( DLBCL ), and 141 patients with chronic lymphocytic leukemia ( CLL ). The population was aged 18 – 85 years ( with a median age of 60 years ), 53 % male and 47 % female . Most of the patients were Caucasians ( 84 %). In the SABRINA study patients with FL received a full dose of a rituximab product by intravenous infusion , followed by RITUXAN HYCELA ( 1,400 mg rituximab / 23,400 Units hyaluronidase human ), in combination with chemotherapy for up to 7 doses ( i . e ., total of 8 doses in combination with chemotherapy ), or as monotherapy for up to 12 doses ( maintenance treatment ). In the MabEase study patients with DLBCL received a full dose of a rituximab product by intravenous infusion , followed by RITUXAN HYCELA ( 1,400 mg rituximab / 23,400 Units hyaluronidase human ), given in combination with chemotherapy for up to 7 doses ( i . e ., up to a total of 8 doses ). In the SAWYER study patients with CLL on part 2 received a full dose of a rituximab product by intravenous infusion , followed by RITUXAN HYCELA ( 1,600 mg rituximab / 26,800 Units hyaluronidase human ) for up to 5 doses , in combination with fludarabine and cyclophosphamide ( i . e ., total of 6 doses ). The most common adverse reactions ( ≥ 20 %) of RITUXAN HYCELA observed in patients with FL on the SABRINA study were : infections , neutropenia , nausea , constipation , cough , and fatigue . The most common adverse reactions ( ≥ 20 %) of RITUXAN HYCELA observed in patients with DLBCL on the MabEase study were : infections , neutropenia , alopecia , nausea , and anemia . The most common adverse reactions ( ≥ 20 %) of RITUXAN HYCELA observed in patients with CLL on part 2 of the SAWYER study were : infections , neutropenia , nausea , thrombocytopenia , pyrexia , vomiting , and injection site erythema .
Administration-related reactions ( ARRs ) Administration-related reactions ( ARRs ) with RITUXAN HYCELA were defined as all the adverse reactions related to the administration of RITUXAN HYCELA within the 24 hours post injection . The incidence of ARRs with RITUXAN HYCELA was 34 % in FL / DLBCL in combination with chemotherapy with injection site erythema ( 5 %), chills ( 3 %), dyspnea , erythema , flushing , injection site pain , nausea , pruritus , pyrexia , rash , and throat irritation ( 2 % each ) being the most common ARRs . The incidence of ARRs in FL maintenance setting was 20 %. The most common ARRs were injection site erythema ( 7 %), erythema ( 4 %), injection site pain / edema , myalgia , and rash ( 2 % each ). The incidence of ARRs with RITUXAN HYCELA in CLL was 44 %. With the exception of Local Cutaneous Reactions , the incidence and profile of adverse reactions reported for RITUXAN HYCELA were comparable with those for rituximab . The overall incidence of adverse reactions for intravenous rituximab versus RITUXAN HYCELA in combination with chemotherapy for FL / DLBCL was 93 % versus 95 % ( BSA ≤ 1.73 m 2 ), 89 % versus 93 %
( 1.73 < BSA ≤ 1.92 m 2 ), and 94 % versus 94 % ( BSA > 1.92 m 2 ). The overall incidence of adverse reactions for rituximab versus RITUXAN HYCELA in CLL was 89 % versus 100 % ( BSA ≤ 1.81 m 2 ), 97 % versus 88 % ( 1.82 < BSA ≤ 1.99 m 2 ), and 88 % versus 93 % ( BSA > 2.00 m 2 ).
Summary of Clinical Trial Experience in Follicular Lymphoma ( FL ) The data in Table 1 were obtained in the SABRINA study , a two-stage randomized , controlled study in patients with previously untreated FL . The study compared patients receiving RITUXAN HYCELA ( 1,400 mg rituximab / 23,400 Units hyaluronidase human ; n = 197 ) with patients receiving a rituximab product by intravenous infusion ( 375 mg / m 2 ; n = 210 ), both in combination with CHOP or CVP followed by maintenance treatment with RITUXAN HYCELA or a rituximab product by intravenous infusion . The majority of patients completed all 8 cycles of combination treatment with chemotherapy ( 91 % RITUXAN HYCELA vs . 90 % rituximab ). In addition , 69 % of patients in each of the treatment groups completed all 20 cycles of combination plus maintenance treatment . In both RITUXAN HYCELA and rituximab groups , patients experienced similar median duration of exposure ( 27.1 months for each arm ). Across the two stages , the overall demographics and baseline characteristics were balanced between the treatment groups . However , there were more female patients ( 53 %) randomized in the study than male patients ( 47 %) and a higher proportion of females were randomized to receive RITUXAN HYCELA ( 59 % female ) compared with the rituximab group ( 48 %). The treatment groups in the combined Stage 1 and 2 population were otherwise balanced in regard to baseline demographics , characterized by a median age of 57 years ( 56.0 years [ range 28 – 85 years ] for RITUXAN HYCELA and 57 years [ range 28 – 86 years ] for rituximab ) and median BSA of 1.83 m 2 ( 1.80 and 1.84 m 2 for RITUXAN HYCELA and rituximab , respectively ).
The incidence of all adverse reactions was 96 % for RITUXAN HYCELA vs . 95 % for rituximab ( Table 1 ). Grade 3 – 4 adverse reactions were reported in 55 % of patients receiving RITUXAN HYCELA vs . 53 % in patients receiving rituximab . Serious adverse reactions were reported in 37 % of patients receiving RITUXAN HYCELA vs . 34 % of patients receiving rituximab . The most common adverse reactions ( occurring in ≥ 20 % of patients in any arm ) were infections , neutropenia , nausea , constipation , cough , and fatigue . A total of 36 patients died , including 14 / 197 patients ( 7 %) who received RITUXAN HYCELA and 22 / 210 patients ( 10 %) who received rituximab . Of these 36 patients , 19 patients ( 7 patients RITUXAN HYCELA [ 4 %] vs . 12 patients rituximab [ 6 %]) died due to adverse reactions and 13 patients ( 6 patients RITUXAN HYCELA [ 3 %] vs . 7 patients rituximab [ 3 %]) died due to disease progression . The incidence of administration-related reactions ( ARRs ) due to the subcutaneous route of administration associated with RITUXAN HYCELA was assessed in combination with chemotherapy and during maintenance . Thirty patients ( 15 %) experienced an ARR during the first administration of RITUXAN HYCELA ( Cycle 2 ). Incidence of ARRs generally decreased at subsequent cycles with 18 patients ( 9 %) reporting ARR at Cycle 3 , 13 patients ( 7 %) at Cycle 4 , 11 patients ( 6 %) at Cycles 5 and 6 , 12 patients ( 7 %) at Cycle 7 , and 8 patients ( 4 %) at Cycle 8 . During RITUXAN HYCELA monotherapy in the maintenance setting the incidence of ARRs at each cycle was ≤ 7 % and was observed in 24 patients ( 14 %) overall . Grade 1 – 2 ARRs constituted 96 % of the overall ARRs . Grade 3 ARRs were reported during the first administration of RITUXAN HYCELA at Cycle 2 by 2 patients . Of the reported ARRs , local cutaneous reactions with RITUXAN HYCELA were reported in 32 patients . These events resolved within a median of 2 days from the onset ( range 1 to 37 days ). Majority of these reactions were Grade 1 and 2 and were observed in 31 patients ( 16 %).
Table 1 : Incidence of Adverse Reactions in ≥ 5 % of Patients with Previously Untreated Follicular Lymphoma Receiving RITUXAN HYCELA or Rituximab in Combination with CHOP or CVP and as Monotherapy for Maintenance Treatment
Body System / Adverse Reactions
RITUXAN HYCELA ( n = 197 )
All AEs %
Grade 3 – 4 %
All AEs %
Rituximab ( n = 210 )
Grade 3 – 4 %
Gastrointestinal Disorders |
Nausea |
31 |
0 |
22 |
0 |
Constipation |
25 |
0 |
26 |
< 1 |
Diarrhea |
18 |
2 |
16 |
< 1 |
Abdominal Pain |
14 |
0 |
12 |
< 1 |
Vomiting |
14 |
0 |
12 |
< 1 |
Dyspepsia |
8 |
0 |
7 |
0 |
Stomatitis |
6 |
0 |
5 |
0 |
Abdominal Pain Upper |
5 |
0 |
5 |
0 |
General Disorders and Administration |
Site Conditions |
Fatigue |
20 |
0 |
18 |
< 1 |
Asthenia |
17 |
1 |
13 |
0 |
Pyrexia |
15 |
< 1 |
16 |
< 1 |
Injection Site Erythema |
13 |
0 |
0 |
0 |
Injection Site Pain |
8 |
0 |
0 |
0 |
Chills |
8 |
0 |
9 |
0 |
Chest Pain |
6 |
1 |
3 |
0 |
Edema Peripheral |
5 |
< 1 |
6 |
0 |
Mucosal Inflammation |
5 |
1 |
6 |
< 1 |
Influenza Like Illness 3 |
0 |
6 |
0 |
Infections Upper Respiratory |
|
|
|
Tract Infection |
15 |
< 1 |
10 |
0 |
Pneumonia |
11 |
5 |
4 |
2 |
Nasopharyngitis |
10 |
0 |
10 |
0 |
Bronchitis |
8 |
< 1 |
8 |
< 1 |
Urinary Tract Infection |
8 |
1 |
14 |
< 1 |
Sinusitis |
7 |
< 1 |
4 |
0 |
Conjunctivitis |
5 |
0 |
5 |
0 |
Influenza |
4 |
0 |
6 |
< 1 |
Blood and Lymphatic System Disorders |
Neutropenia |
32 |
26 |
27 |
21 |
Anemia |
15 |
5 |
13 |
0 |
Febrile Neutropenia 8 |
7 |
6 |
6 |
Leukopenia |
6 |
4 |
11 |
2 |
Musculoskeletal and Connective Tissue |
Disorders |
Arthralgia |
13 |
< 1 |
10 |
0 |
Bone Pain |
10 |
< 1 |
8 |
0 |
Pain In Extremity |
10 |
0 |
5 |
0 |
Back Pain |
9 |
< 1 |
12 |
< 1 |
Muscle Spasms |
8 |
0 |
3 |
0 |
Myalgia |
8 |
0 |
5 |
0 |
Nervous System Disorders |
Paresthesia |
16 |
0 |
12 |
0 |
Headache |
13 |
0 |
9 |
0 |
Neuropathy Peripheral |
12 |
2 |
14 |
< 1 |
Dizziness |
7 |
0 |
7 |
0 |
Skin and Subcutaneous Tissue Disorders |
Alopecia |
14 |
< 1 |
10 |
< 1 |
Pruritus |
10 |
0 |
12 |
< 1 |
Rash |
10 |
0 |
7 |
0 |
Erythema |
9 |
0 |
5 |
0 |
Respiratory , Thoracic and Mediastinal |
Disorders |
Cough |
23 |
0 |
13 |
< 1 |
Dyspnea |
11 |
1 |
8 |
2 |
Oropharyngeal Pain 9 |
0 |
8 |
0 |
Psychiatric Disorders |
|
|
|
Insomnia |
9 |
0 |
9 |
0 |
Vascular Disorders |
Hypertension |
6 |
1 |
6 |
0 |