2008年12月8日，在美国血液病学会年会上葛兰素史克和Genmab公司公布了其合作开发的抗CD20单克隆抗体ofatumumab（Arzerra）用于成人慢性淋巴细胞白血病（CLL）的最新临床研究结果。数据来自于138例不适合使用现有疗法或经现有疗法治疗无效的CLL患者。结果显示，经化疗联合alemtuzumab方案治疗失败的患者中有58%经本品治疗有效，经化学治疗失败而又不适于使用alemtuzumab治疗的患者中47%经本品治疗有效。 最常见的严重不良反应为感染，发生率为25%，其中有1例出现致命性的进行性多灶性脑白质病。在为期8周的治疗期间中，上述治疗组中分别有7%和3%的患者死亡。前一组患者的中位生存期为13.7个月，中位疾病无进展生存期为5.7个月，后一组患者的中位生存期为15.4个月，中位疾病无进展生存期为5.9个月。 ARZERRA-靶向CD20的单克隆抗体(ofatumumab)注射液 HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ARZERRA safely and effectively. See full prescribing information for ARZERRA. ARZERRA (ofatumumab) Injection, for intravenous infusion Initial U.S. Approval: 2009 RECENT MAJOR CHANGES Dosage and Administration, Preparation and Administration (2.5) 04/2011 Warnings and Precautions, HepatitisB Infection and Reactivation (5.4) 09/2011 INDICATIONS AND USAGE ARZERRA (ofatumumab) is a CD20-directed cytolytic monoclonal antibody 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. No data demonstrate an improvement in disease-related symptoms or increased survival with ARZERRA. (1, 14) DOSAGE AND ADMINISTRATION Dilute and administer as an intravenous infusion. Do not administer as an intravenous push or bolus. (2.1) Recommended dosage and schedule is 12doses administered as follows: 300mg initial dose, followed 1week later by 2,000mg weekly for 7doses, followed 4weeks later by 2,000mg every 4weeks for 4doses. (2.1) Premedicate with oral acetaminophen, oral or intravenous antihistamine, and intravenous corticosteroid. (2.4) DOSAGE FORMS AND STRENGTHS 100mg/5mL single-use vial. (3) 1,000mg/50mL single-use vial. (3) CONTRAINDICATIONS None. (4) WARNINGS AND PRECAUTIONS Infusion Reactions: Premedicate with an intravenous corticosteroid (as appropriate), an oral analgesic, and an oral or intravenous antihistamine. Monitor patients closely during infusions. Interrupt infusion if infusion reactions occur. (2.3, 2.4, 5.1) Cytopenias: Monitor blood counts at regular intervals for neutropenia and thrombocytopenia. (5.2) Progressive Multifocal Leukoencephalopathy (PML): Monitor neurologic function and discontinue ARZERRA if PML is suspected. (5.3) Hepatitis B Infection and Reactivation: Screen high-risk patients. Discontinue ARZERRA in patients who develop viral hepatitis or reactivation of viral hepatitis. (5.4) ADVERSE REACTIONS Most common adverse reactions (≥10%) were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. (6) To report SUSPECTED ADVERSE REACTIONS, contact GlaxoSmithKline at 1-888-825-5249 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. USE IN SPECIFIC POPULATIONS Pregnancy: Based on animal data, may cause fetal harm. (8.1) Nursing mothers: Published data suggest that consumption of breast milk does not result in substantial absorption of maternal antibodies into circulation. (8.3) See 17 for PATIENT COUNSELING INFORMATION  Revised: 09/2011 FULL PRESCRIBING 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)]. No data demonstrate an improvement in disease-related symptoms or increased survival with ARZERRA. 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Dosage Regimen Do not administer as an intravenous push or bolus. Premedicate before each infusion [see Dosage and Administration (2.4)]. Administer with an in-line filter set supplied with product. The recommended dosage and schedule is 12doses administered as follows: 300mg initial dose (Dose1), followed 1week later by 2,000mg weekly for 7doses (Doses2 through 8), followed 4weeks later by 2,000mg every 4weeks for 4doses (Doses9 through 12) 2.2 Administration Prepare all doses in 1,000mL of 0.9% Sodium Chloride Injection, USP [see Dosage and Administration (2.5)]. Dose 1: Initiate infusion at a rate of 3.6mg/hour (12mL/hour). Dose 2: Initiate infusion at a rate of 24mg/hour (12mL/hour). Doses 3 through 12: Initiate infusion at a rate of 50mg/hour (25mL/hour). In the absence of infusional toxicity, the rate of infusion may be increased every 30minutes as described in Table1. Do not exceed the infusion rates in Table1. Table 1. Infusion Rates for ARZERRA Interval After Start of Infusion (min) Dose1a (mL/hour) Dose2b (mL/hour) Doses 3-12b (mL/hour) 0-30 12 12 25 31-60 25 25 50 61-90 50 50 100 91-120 100 100 200 >120 200 200 400 a Dose 1 = 300mg (0.3mg/mL). b Doses 2 and 3-12 = 2,000mg (2mg/mL). 2.3 Dose Modification Interrupt infusion for infusion reactions of any severity [see Warnings and Precautions (5.1)]. For Grade4 infusion reactions, do not resume the infusion. For Grade1, 2, or 3 infusion reaction, if the infusion reaction resolves or remains less than or equal to Grade2, resume infusion with the following modifications according to the initial Grade of the infusion reaction. Grade1 or 2: Infuse at one-half of the previous infusion rate. Grade3: Infuse at a rate of 12mL/hour. After resuming the infusion, the infusion rate may be increased according to Table1 above, based on patient tolerance. 2.4 Premedication Premedicate 30minutes to 2hours prior to each dose with oral acetaminophen 1,000mg (or equivalent), oral or intravenous antihistamine (cetirizine 10mg or equivalent), and intravenous corticosteroid (prednisolone 100mg or equivalent). Do not reduce corticosteroid dose for Doses 1, 2, and 9. Corticosteroid dose may be reduced as follows for Doses 3 through 8 and 10 through 12: Doses 3 through 8: Gradually reduce corticosteroid dose with successive infusions if a Grade3 or greater infusion reaction did not occur with the preceding dose. Doses 10 through 12: Administer prednisolone 50mg to 100mg or equivalent if a Grade3 or greater infusion reaction did not occur with Dose9. 2.5 Preparation and Administration Do not shake product. Inspect parenteral drug products visually for particulate matter and discoloration prior to administration. ARZERRA should be a clear to opalescent, colorless solution and may contain a small amount of visible translucent-to-white, amorphous, ofatumumab particles. The solution should not be used if discolored or cloudy, or if foreign particulate matter is present. Preparation of Solution: 300-mg dose: Withdraw and discard 15mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 5mL from each of 3single-use 100mg vials of ARZERRA and add to the bag. Mix diluted solution by gentle inversion. 2,000-mg dose: Withdraw and discard 100mL from a 1,000-mL bag of 0.9% Sodium Chloride Injection, USP. Withdraw 50mL from each of 2single-use 1,000mg vials of ARZERRA and add to the bag. Mix diluted solution by gentle inversion. Store diluted solution between 2° to 8°C (36° to 46°F). No incompatibilities between ARZERRA and polyvinylchloride or polyolefin bags and administration sets have been observed. Administration Instructions: Do not mix ARZERRA with, or administer as an infusion with, other medicinal products. Administer using an infusion pump with an administration set and the provided in-line filter set. Flush the intravenous line with 0.9% Sodium Chloride Injection, USP before and after each dose. Start infusion within 12hours of preparation. Discard prepared solution after 24hours. 3 DOSAGE FORMS AND STRENGTHS 100mg/5mL single-use vial. 1,000mg/50mL single-use vial. 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 2infusions [see Adverse Reactions (6.1)]. Premedicate with acetaminophen, an antihistamine, and a corticosteroid [see Dosage and Administration (2.1, 2.4)]. 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)]. In a study of patients with moderate to severe chronic obstructive pulmonary disease, an indication for which ARZERRA is not approved, 2 of 5patients developed Grade3 bronchospasm during infusion. 5.2 Cytopenias Prolonged (≥1week) 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 Grade3 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 eva luation for PML including consultation with a neurologist, brain MRI, and lumbar puncture. 5.4 HepatitisB Infection and Reactivation Fulminant and fatal hepatitisB 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 hepatitisB for clinical and laboratory signs of active HBV infection during treatment with ARZERRA and for 6 to 12months 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 eva luation 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: Infusion Reactions [see Warnings and Precautions (5.1)] Cytopenias [see Warnings and Precautions (5.2)] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.3)] Hepatitis B Reactivation [see Warnings and Precautions (5.4)] Intestinal Obstruction [see Warnings and Precautions (5.5)] The most common adverse reactions (≥10%) in Study1 were neutropenia, pneumonia, pyrexia, cough, diarrhea, anemia, fatigue, dyspnea, rash, nausea, bronchitis, and upper respiratory tract infections. The most common serious adverse reactions in Study1 were infections (including pneumonia and sepsis), neutropenia, and pyrexia. Infections were the most common adverse reactions leading to drug discontinuation in Study1. 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 eva luated in 181patients with relapsed or refractory CLL in 2open-label, non-randomized, single-arm studies. In these studies, ARZERRA was administered at 2,000mg beginning with the second dose for 11doses (Study1 [n=154]) or 3doses (Study2 [n=27]). The data described in Table2 and other sections below are derived from 154patients in Study1. All patients received 2,000mg weekly from the second dose onward. Ninety percent of patients received at least 8infusions of ARZERRA and 55% received all 12infusions. The median age was 63years (range: 41 to 86years), 72% were male, and 97% were White. Table 2. Incidence of All Adverse Reactions Occurring in ≥5% of Patients in Study1 and in the Fludarabine- and Alemtuzumab-Refractory Subset of Study1 (MedDRA 9.0) Body System/Adverse Event Total Population (n=154) Fludarabine- and Alemtuzumab-Refractory (n=59) All Grades % Grade ≥3 % All Grades % Grade ≥3 % Infections and infestations Pneumoniaa 23 14 25 15 Upper respiratory tract infection 11 0 3 0 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 (300mg), 29% on the day of the second infusion (2,000mg), and less frequently during subsequent infusions. Infections: A total of 108patients (70%) experienced bacterial, viral, or fungal infections. A total of 45patients (29%) experienced ≥Grade3 infections, of which 19 (12%) were fatal. The proportion of fatal infections in the fludarabine- and alemtuzumab-refractory group was 17%. Neutropenia: Of 108patients with normal neutrophil counts at baseline, 45 (42%) developed ≥Grade3 neutropenia. Nineteen (18%) developed Grade4 neutropenia. Some patients experienced new onset Grade4 neutropenia >2weeks in duration. 6.2 Immunogenicity There is a potential for immunogenicity with therapeutic proteins such as ofatumumab. Serum samples from patients with CLL in Study1 were tested by enzyme-linked immunosorbent assay (ELISA) for anti-ofatumumab antibodies during and after the 24-week treatment period. Results were negative in 46patients after the 8th infusion and in 33patients 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. 7 DRUG INTERACTIONS No formal drug-drug interaction studies have been conducted with ARZERRA. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category C: There are no adequate or well-controlled studies of ofatumumab in pregnant women. A reproductive study in pregnant cynomolgus monkeys that received ofatumumab at doses up to 3.5times the recommended human dose of ofatumumab did not demonstrate maternal toxicity or teratogenicity. Ofatumumab crossed the placental barrier, and fetuses exhibited depletion of peripheral Bcells and decreased spleen and placental weights. ARZERRA should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. There are no human or animal data on the potential short- and long-term effects of perinatal B-cell depletion in offspring following in utero exposure to ofatumumab. Ofatumumab does not bind normal human tissues other than Blymphocytes. It is not known if binding occurs to unique embryonic or fetal tissue targets. In addition, the kinetics of B-lymphocyte recovery are unknown in offspring with B-cell depletion [see Nonclinical Toxicology (13.3)]. 8.3 Nursing Mothers It is not known whether ofatumumab is secreted in human milk; however, human IgG is secreted in human milk. Published data suggest that neonatal and infant consumption of breast milk does not result in substantial absorption of these maternal antibodies into circulation. Because the effects of local gastrointestinal and limited systemic exposure to ofatumumab are unknown, caution should be exercised when ARZERRA is administered to a nursing woman. 8.4 Pediatric Use Safety and effectiveness of ARZERRA have not been established in children. 8.5 Geriatric Use Clinical studies of ARZERRA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects [see Clinical Pharmacology (12.3)]. 8.6 Renal Impairment No formal studies of ARZERRA in patients with renal impairment have been conducted [see Clinical Pharmacology (12.3)]. 8.7 Hepatic Impairment No formal studies of ARZERRA in patients with hepatic impairment have been conducted. 10 OVERDOSAGE No data are available regarding overdosage with ARZERRA. 11 DESCRIPTION ARZERRA (ofatumumab) is an IgG1κ human monoclonal antibody with a molecular weight of approximately 149kDa. The antibody was generated via transgenic mouse and hybridoma technology and is produced in a recombinant murine cell line (NS0) using standard mammalian cell cultivation and purification technologies. ARZERRA is a sterile, clear to opalescent, colorless, preservative-free liquid concentrate for intravenous administration. ARZERRA is supplied at a concentration of 20mg/mL in single-use vials. Each single-use vial contains either 100mg ofatumumab in 5mL of solution or 1,000mg ofatumumab in 50mL of solution. Inactive ingredients include: 10mg/mL arginine, diluted hydrochloric acid, 0.019mg/mL edetate disodium, 0.2mg/mL polysorbate80, 6.8mg/mL sodium acetate, 2.98mg/mL sodium chloride, and Water for Injection, USP. The pH is 5.5. 12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ofatumumab binds specifically to both the small and large extracellular loops of the CD20 molecule. The CD20 molecule is expressed on normal Blymphocytes (pre-B- to mature B-lymphocyte) and on B-cell CLL. The CD20 molecule is not shed from the cell surface and is not internalized following antibody binding. The Fab domain of ofatumumab binds to the CD20 molecule and the Fc domain mediates immune effector functions to result in B-cell lysis in vitro. Data suggest that possible mechanisms of cell lysis include complement-dependent cytotoxicity and antibody-dependent, cell-mediated cytotoxicity. 12.2 Pharmacodynamics In patients with CLL refractory to fludarabine and alemtuzumab, the median decrease in circulating CD19-positive Bcells was 91% (n=50) with the 8th infusion and 85% (n=32) with the 12th infusion. The time to recovery of lymphocytes, including CD19-positive Bcells, to normal levels has not been determined. 12.3 Pharmacokinetics Pharmacokinetic data were obtained from 146patients with refractory CLL who received a 300-mg initial dose followed by 7weekly and 4monthly infusions of 2,000mg. The Cmax and AUC(0-∞) after the 8th infusion in Study1 were approximately 40% and 60% higher than after the 4th infusion in Study2. The mean volume of distribution at steady-state (Vss) values ranged from 1.7 to 5.1L. Ofatumumab is eliminated through both a target-independent route and a Bcell-mediated route. Ofatumumab exhibited dose-dependent clearance in the dose range of 100 to 2,000mg. Due to the depletion of Bcells, the clearance of ofatumumab decreased substantially after subsequent infusions compared to the first infusion. The mean clearance between the 4th and 12th infusions was approximately 0.01L/hr and exhibited large inter-subject variability with CV% greater than 50%. The mean t1/2 between the 4th and 12th infusions was approximately 14days (range: 2.3 to 61.5days). Special Populations: Cross-study analyses were performed on data from patients with a variety of conditions, including 162patients with CLL, who received multiple infusions of ARZERRA as a single agent at doses ranging from 100 to 2,000mg. The effects of various covariates (e.g., body size [weight, height, body surface area], age, gender, baseline creatinine clearance) on ofatumumab pharmacokinetics were assessed in a population pharmacokinetic analysis. Body Weight: Volume of distribution and clearance increased with body weight. However, this increase was not clinically significant. No dosage adjustment is recommended based on body weight. Age: Age did not significantly influence ofatumumab pharmacokinetics in patients ranging from 21 to 86years of age. No pharmacokinetic data are available in pediatric patients. Gender: Gender had a modest effect on ofatumumab pharmacokinetics (14% to 25% lower clearance and volume of distribution in female patients compared to male patients) in a cross-study population analysis (41% of the patients in this analysis were male and 59% were female). These effects are not considered clinically important, and no dosage adjustment is recommended. Renal Impairment: Creatinine clearance at baseline did not have a clinically important effect on ofatumumab pharmacokinetics in patients with calculated creatinine clearance values ranging from 33 to 287mL/min. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility No carcinogenicity or mutagenicity studies of ofatumumab have been conducted. In a repeat-dose toxicity study, no tumorigenic or unexpected mitogenic responses were noted in cynomolgus monkeys treated for 7months with up to 3.5times the human dose of ofatumumab. Effects on male and female fertility have not been eva luated in animal studies. 13.3 Reproductive and Developmental Toxicology Pregnant cynomolgus monkeys dosed with 0.7 or 3.5times the human dose of ofatumumab weekly during the period of organogenesis (gestation days 20 to 50) had no maternal toxicity or teratogenicity. Both dose levels of ofatumumab depleted circulating Bcells in the dams, with signs of initial Bcell recovery 50days after the final dose. Following Caesarean section at gestational day100, fetuses from ofatumumab-treated dams exhibited decreases in mean peripheral B-cell counts (decreased to approximately 10% of control values), splenic B-cell counts (decreased to approximately 15 to 20% of control values), and spleen weights (decreased by 15% for the low-dose and by 30% for the high-dose group, compared to control values). Fetuses from treated dams exhibiting anti-ofatumumab antibody responses had higher Bcell counts and higher spleen weights compared to the fetuses from other treated dams, indicating partial recovery in those animals developing anti-ofatumumab antibodies. When compared to control animals, fetuses from treated dams in both dose groups had a 10% decrease in mean placental weights. A 15% decrease in mean thymus weight compared to the controls was also observed in fetuses from dams treated with 3.5 times the human dose of ofatumumab. The biological significance of decreased placental and thymic weights is unknown. The kinetics of B-lymphocyte recovery and the potential long-term effects of perinatal B-cell depletion in offspring from ofatumumab-treated dams have not been studied in animals. 14 CLINICAL STUDIES Study1 was a single-arm, multicenter study in 154patients with relapsed or refractory CLL. ARZERRA was administered by intravenous infusion according to the following schedule: 300mg (Week 0), 2,000mg weekly for 7infusions (Weeks 1 through 7), and 2,000mg every 4weeks for 4infusions (Weeks 12 through 24). Patients with CLL refractory to fludarabine and alemtuzumab (n=59) comprised the efficacy population. Drug refractoriness was defined as failure to achieve at least a partial response to, or disease progression within 6months of, the last dose of fludarabine or alemtuzumab. The main efficacy outcome was durable objective tumor response rate. Objective tumor responses were determined using the 1996 National Cancer Institute Working Group (NCIWG) Guidelines for CLL. In patients with CLL refractory to fludarabine and alemtuzumab, the median age was 64years (range: 41 to 86years), 75% were male, and 95% were White. The median number of prior therapies was 5; 93% received prior alkylating agents, 59% received prior rituximab, and all received prior fludarabine and alemtuzumab. Eighty-eight percent of patients received at least 8infusions of ARZERRA and 54% received 12infusions. The investigator-determined overall response rate in patients with CLL refractory to fludarabine and alemtuzumab was 42% (99% CI: 26, 60) with a median duration of response of 6.5months (95% CI: 5.8, 8.3). There were no complete responses. Anti-tumor activity was also observed in additional patients in Study1 and in a multicenter, open-label, dose-escalation study (Study2) conducted in patients with relapsed or refractory CLL. 16 HOW SUPPLIED/STORAGE AND HANDLING ARZERRA (ofatumumab) is a sterile, clear to opalescent, colorless, preservative-free liquid concentrate (20mg/mL) for dilution and intravenous administration provided in single-use glass vials with a latex-free rubber stopper and an aluminum overseal. Each vial contains either 100mg ofatumumab in 5mL of solution or 1,000mg ofatumumab in 50mL of solution. ARZERRA is available as follows: Carton Contents NDC 3 single-use 100mg/5mL vials with 2 in-line filter sets Vial: NDC 0173-0821-02 Carton of 3 vials: NDC 0173-0821-33 1 single-use 1,000mg/50mL vial with 2 in-line filter sets Vial and Carton: NDC 0173-0821-01 Store ARZERRA refrigerated between 2° to 8°C (36° to 46°F). Do not freeze. Vials should be protected from light. CHMP建议批准GSK单抗药Arzerra用于慢性淋巴细胞白血病的治疗 2014年5月25日,葛兰素史克（GSK）单抗药物Arzerra（ofatumumab）获得了欧洲药品管理局（EMA）人用医药产品委员会（CHMP）的积极意见。CHMP建议批准Arzerra联合苯丁酸氮芥（chlorambucil）或苯达莫司汀（bendamustine），用于初治及不适合氟达拉滨（fludarabine）化疗的慢性淋巴细胞白血病（CLL）患者的治疗。 CHMP的积极意见，是基于在不适合氟达拉滨化疗方案的初治CLL患者中开展的2项临床试验的数据。 OMB110911（COMPLEMENT1）是一项随机、开放标签、平行组、多中心、关键III期研究，在超过400例初治CLL患者中开展，研究中将ofatumumab+苯丁酸氮芥（chlorambucil）组合疗法与苯丁酸氮芥单药疗法进行了对比。数据表明，与苯丁酸氮芥单药疗法相比，组合疗法显著改善了疾病无进展生存期（PFS，22.4个月 vs 13.1个月，p＜0.001）。OMB115991是一项单组、多中心II期研究，评估了ofatumumab+苯达莫司汀组合疗法的疗效。 此前，Arzerra已于2014年4月获FDA批准，联合苯丁酸氮芥（chlorambucil）用于初治且不适和氟达拉滨（fludarabine）化疗的慢性淋巴细胞白血病（CLL）患者的一线治疗。Arzerra由葛兰素史克（GSK）和Genmab联合开发。 关于Arzerra（ofatumumab）： Arzerra（ofatumumab）是一种创新的全人源化单克隆抗体，靶向B细胞表面CD20分子的一个抗原表位，该表位包含了CD20分子的胞外大环和小环结构。 Arzerra分别于2009年和2010年获FDA和EMA批准，用于对标准药物【阿仑单抗（alemtuzumab，Campath）或氟达拉滨（fludarabine）】治疗无应答的慢性淋巴细胞白血病（CLL）患者的治疗。 目前，Arzerra尚未获批用于弥漫性大B细胞淋巴瘤（DLBCL）的治疗.