ASH News Daily - Sunday, December 11, 2011 - (Page B-20)

Page B–20 ® ASH NewS DAily Treatment Regimen Information Blood is one of the few journals that require inclusion of information needed for actual administration of the treatment regimen in practice in all clinical trials that report on a parenteral or high-intensity treatment regimen. The authors are asked to include this information as a supplemental file. Patient Information Patients interested in obtaining a copy of an access-controlled article in Blood that may be helpful to their situation may do so by emailing a request to the Blood Publishing Office at publishing@ hematology.org. Sunday, December 11, 2011 Clinicians «« From Page B-14 Abstracts «« From Page B-16 board certification, enhancing their knowledge on the subject matter, and improving the care they provide to patients. “Free by EIC” In every issue, the editor-in-chief selects five articles that will be made available to the public, without a subscription embargo. The free articles for the most recent issue are featured prominently on the Blood homepage and older, free articles are archived on the site. In addition, every article in the journal is publically accessible 12 months after its publication date. Graduate Student Jin Yuan Monday, December 12: 11:45 a.m., San Diego Convention Center, Room 25 Hematopoietic Stem and Progenitor Biology: Epigenetic Regulation of Hematopoietic Stem and Progenitor Cells Lethal Myelofibrosis Induced by Bmi1-Deficient Hematopoietic Cells Unveils a Tumor Suppressor Function of the Polycomb Group Genes Abstract #390 Postdoctoral Fellow B:22.5” Kathryn Roberts, PhD Today: 4:30 p.m., San T:21” Diego Convention Center, Room 28 S:19” ABCD Leukemias – Biology, Cytogenetics and Molecular Markers in Diagnosis and Prognosis: Next Generation Sequencing Discoveries in Leukemia Novel Chromosomal Rearrangements and Sequence Mutations in High-Risk Ph-Like Acute Lymphoblastic Leukemia Abstract #67 BRIEF SUMMARY ARZERRA® (ofatumumab) Injection, for intravenous infusion The following is a brief summary only; see full prescribing information for complete product information. 1 INDICATIONS AND USAGE ARZERRA® (ofatumumab) is indicated for the treatment of patients with chronic lymphocytic leukemia (CLL) refractory to fludarabine and alemtuzumab. The effectiveness of ARZERRA is based on the demonstration of durable objective responses [see Clinical Studies (14) of full prescribing information]. No data demonstrate an improvement in disease-related symptoms or increased survival with ARZERRA. 4 CONTRAINDICATIONS None. 5 WARNINGS AND PRECAUTIONS 5.1 Infusion Reactions ARZERRA can cause serious infusion reactions manifesting as bronchospasm, dyspnea, laryngeal edema, pulmonary edema, flushing, hypertension, hypotension, syncope, cardiac ischemia/infarction, back pain, abdominal pain, pyrexia, rash, urticaria, and angioedema. Infusion reactions occur more frequently with the first 2 infusions [see Adverse Reactions (6.1)]. Premedicate with acetaminophen, an antihistamine, and a corticosteroid [see Dosage and Administration (2.1, 2.4) of full prescribing information]. Interrupt infusion for infusion reactions of any severity. Institute medical management for severe infusion reactions including angina or other signs and symptoms of myocardial ischemia [see Dosage and Administration (2.3) of full prescribing information]. In a study of patients with moderate to severe chronic obstructive pulmonary disease, an indication for which ARZERRA is not approved, 2 of 5 patients developed Grade 3 bronchospasm during infusion. 5.2 Cytopenias Prolonged (≥1 week) severe neutropenia and thrombocytopenia can occur with ARZERRA. Monitor complete blood counts (CBC) and platelet counts at regular intervals during therapy, and increase the frequency of monitoring in patients who develop Grade 3 or 4 cytopenias. 5.3 Progressive Multifocal Leukoencephalopathy Progressive multifocal leukoencephalopathy (PML), including fatal PML, can occur with ARZERRA. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. Discontinue ARZERRA if PML is suspected, and initiate evaluation for PML including consultation with a neurologist, brain MRI, and lumbar puncture. 5.4 Hepatitis B Infection and Reactivation Fulminant and fatal hepatitis B virus (HBV) infection and reactivation can occur in patients following treatment with ARZERRA. Screen patients at high risk of HBV infection before initiation of ARZERRA. Closely monitor carriers of hepatitis B for clinical and laboratory signs of active HBV infection during treatment with ARZERRA and for 6 to 12 months following the last infusion of ARZERRA. Discontinue ARZERRA in patients who develop viral hepatitis or reactivation of viral hepatitis, and institute appropriate treatment. Insufficient data exist regarding the safety of administration of ARZERRA in patients with active hepatitis. 5.5 Intestinal Obstruction Obstruction of the small intestine can occur in patients receiving ARZERRA. Perform a diagnostic evaluation if obstruction is suspected. 5.6 Immunizations The safety of immunization with live viral vaccines during or following administration of ARZERRA has not been studied. Do not administer live viral vaccines to patients who have recently received ARZERRA. The ability to generate an immune response to any vaccine following administration of ARZERRA has not been studied. 6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: • nfusion Reactions [see Warnings and Precautions (5.1)] I • ytopenias [see Warnings and Precautions (5.2)] C • rogressive Multifocal Leukoencephalopathy [see Warnings and P Precautions (5.3)] • epatitis B Reactivation [see Warnings and Precautions (5.4)] H • ntestinal Obstruction [see Warnings and Precautions (5.5)] I The most common adverse reactions (≥10%) in Study 1 were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. The most common serious adverse reactions in Study 1 were infections (including pneumonia and sepsis), neutropenia, and pyrexia. Infections were the most common adverse reactions leading to drug discontinuation in Study 1. 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 practice. The safety of monotherapy with ARZERRA was evaluated in 181 patients with relapsed or refractory CLL in 2 open-label, non-randomized, single-arm studies. In these studies, ARZERRA was administered at 2,000 mg beginning with the second dose for 11 doses (Study 1 [n = 154]) or 3 doses (Study 2 [n = 27]). The data described in Table 1 and other sections below are derived from 154 patients in Study 1. All patients received 2,000 mg weekly from the second dose onward. Ninety percent of patients received at least 8 infusions of ARZERRA and 55% received all 12 infusions. The median age was 63 years (range: 41 to 86 years), 72% were male, and 97% were White. Table 1. Incidence of All Adverse Reactions Occurring in ≥5% of Patients in Study 1 and in the Fludarabine- and Alemtuzumab-Refractory Subset of Study 1 (MedDRA 9.0) Total Population (n = 154) Fludarabine- and AlemtuzumabRefractory (n = 59) Grade All ≥3 Grades % % Grade All ≥3 Grades Body System/ % % Adverse Event Infections and infestations Pneumoniaa 23 14 25 15 Upper respiratory tract 11 0 3 0 infection Bronchitis 11 <1 19 2 Sepsisb 8 8 10 10 Nasopharyngitis 8 0 8 0 Herpes zoster 6 1 7 2 Sinusitis 5 2 3 2 Blood and lymphatic system disorders Anemia 16 5 17 8 Psychiatric disorders Insomnia 7 0 10 0 Nervous system disorders Headache 6 0 7 0 Cardiovascular disorders Hypertension 5 0 8 0 Hypotension 5 0 3 0 Tachycardia 5 <1 7 2 Respiratory, thoracic, and mediastinal disorders Cough 19 0 19 0 Dyspnea 14 2 19 5 Gastrointestinal disorders Diarrhea 18 0 19 0 Nausea 11 0 12 0 Skin and subcutaneous tissue disorders Rashc 14 <1 17 2 Urticaria 8 0 5 0 Hyperhidrosis 5 0 5 0 Musculoskeletal and connective tissue disorders Back pain 8 1 12 2 Muscle spasms 5 0 3 0 General disorders and administration site conditions Pyrexia 20 3 25 5 Fatigue 15 0 15 0 Edema peripheral 9 <1 8 2 Chills 8 0 10 0 a Pneumonia includes pneumonia, lung infection, lobar pneumonia, and bronchopneumonia. b Sepsis includes sepsis, neutropenic sepsis, bacteremia, and septic shock. c Rash includes rash, rash macular, and rash vesicular. Infusion Reactions: Infusion reactions occurred in 44% of patients on the day of the first infusion (300 mg), 29% on the day of the second infusion (2,000 mg), and less frequently during subsequent infusions. Infections: A total of 108 patients (70%) experienced bacterial, viral, or fungal infections. A total of 45 patients (29%) experienced ≥Grade 3 infections, of which 19 (12%) were fatal. The proportion of fatal infections in the fludarabine- and alemtuzumab-refractory group was 17%. Neutropenia: Of 108 patients with normal neutrophil counts at baseline, 45 (42%) developed ≥Grade 3 neutropenia. Nineteen (18%) developed Grade 4 neutropenia. Some patients experienced new onset Grade 4 neutropenia >2 weeks in duration. 6.2 Immunogenicity There is a potential for immunogenicity with therapeutic proteins such as ofatumumab. Serum samples from patients with CLL in Study 1 were tested by enzyme-linked immunosorbent assay (ELISA) for anti-ofatumumab antibodies during and after the 24-week treatment period. Results were negative in 46 patients after the 8th infusion and in 33 patients after the 12th infusion. Immunogenicity assay results are highly dependent on several factors including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medications, and underlying disease. For these reasons, comparison of incidence of antibodies to ARZERRA with the incidence of antibodies to other products may be misleading. 

Table of Contents for the Digital Edition of ASH News Daily - Sunday, December 11, 2011

ASH News Daily - Sunday, December 11, 2011

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