|
Imbruvica（ibrutinib capsules 中文药名：依鲁替尼胶囊）美国FDA批准获为罕见血癌新药
Avoid co-administration with strong or moderate CYP3A inhibitors and consider alternative agents with less CYP3A inhibition. Concomitant use of strong CYP3A inhibitors which would be taken chronically (e.g., ritonavir, indinavir, nelfinavir, saquinavir, boceprevir, telaprevir, nefazodone) is not recommended. For short-term use (treatment for 7 days or less) of strong CYP3A inhibitors (e.g., antifungals and antibiotics) consider interrupting IMBRUVICA therapy until the CYP3A inhibitor is no longer needed [see Drug Interactions (7.1)]. Reduce IMBRUVICA dose to 140 mg if a moderate CYP3A inhibitor must be used (e.g., fluconazole, darunavir, erythromycin, diltiazem, atazanavir, aprepitant, amprenavir, fosamprevir, crizotinib, imatinib, verapamil, and ciprofloxacin) [see Drug Interactions (7.1)]. Patients taking concomitant strong or moderate CYP3A inhibitors should be monitored more closely for signs of IMBRUVICA toxicity. 2.5 Dose Modifications for Use in Hepatic Impairment For patients with mild liver impairment (Child-Pugh class A), the recommended dose is 140 mg daily (one capsule). Avoid the use of IMBRUVICA in patients with moderate or severe hepatic impairment (Child-Pugh classes B and C) [see Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)]. 2.6 Missed Dose If a dose of IMBRUVICA is not taken at the scheduled time, it can be taken as soon as possible on the same day with a return to the normal schedule the following day. Extra capsules of IMBRUVICA should not be taken to make up for the missed dose. 3 DOSAGE FORMS AND STRENGTHS 140 mg capsules 4 CONTRAINDICATIONS None 5 WARNINGS AND PRECAUTIONS 5.1 Hemorrhage Fatal bleeding events have occurred in patients treated with IMBRUVICA. Grade 3 or higher bleeding events (subdural hematoma, gastrointestinal bleeding, hematuria and post procedural hemorrhage) have occurred in up to 6% of patients. Bleeding events of any grade, including bruising and petechiae, occurred in approximately half of patients treated with IMBRUVICA. The mechanism for the bleeding events is not well understood. IMBRUVICA may increase the risk of hemorrhage in patients receiving antiplatelet or anticoagulant therapies. Consider the benefit-risk of withholding IMBRUVICA for at least 3 to 7 days pre and post-surgery depending upon the type of surgery and the risk of bleeding [see Clinical Studies (14)]. 5.2 Infections Fatal and non-fatal infections have occurred with IMBRUVICA therapy. Grade 3 or greater infections occurred in 14% to 26% of patients. [See Adverse Reactions (6.1)]. Cases of progressive multifocal leukoencephalopathy (PML) have occurred in patients treated with IMBRUVICA. Monitor patients for fever and infections and evaluate promptly. 5.3 Cytopenias Treatment-emergent Grade 3 or 4 cytopenias including neutropenia (range, 19 to 29%), thrombocytopenia (range, 5 to 17%), and anemia (range, 0 to 9%) occurred in patients treated with IMBRUVICA. Monitor complete blood counts monthly. 5.4 Atrial Fibrillation Atrial fibrillation and atrial flutter (range, 6 to 9%) have occurred in patients treated with IMBRUVICA, particularly in patients with cardiac risk factors, acute infections, and a previous history of atrial fibrillation. Periodically monitor patients clinically for atrial fibrillation. Patients who develop arrhythmic symptoms (e.g., palpitations, lightheadedness) or new onset dyspnea should have an ECG performed. If atrial fibrillation persists, consider the risks and benefits of IMBRUVICA treatment and dose modification [see Dosage and Administration (2.3)]. 5.5 Second Primary Malignancies Other malignancies (range, 5 to 14%) including non-skin carcinomas (range, 1 to 3%) have occurred in patients treated with IMBRUVICA. The most frequent second primary malignancy was non-melanoma skin cancer (range, 4 to 11 %). 5.6 Tumor Lysis Syndrome Tumor lysis syndrome has been reported with IMBRUVICA therapy. Monitor patients closely and take appropriate precautions in patients at risk for tumor lysis syndrome (e.g. high tumor burden). 5.7 Embryo-Fetal Toxicity Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. Ibrutinib caused malformations in rats at exposures 14 times those reported in patients with MCL and 20 times those reported in patients with CLL or WM, receiving the ibrutinib dose of 560 mg per day and 420 mg per day, respectively. Reduced fetal weights were observed at lower exposures. Advise women to avoid becoming pregnant while taking IMBRUVICA. If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus [see Use in Specific Populations (8.1)]. 6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Hemorrhage [see Warnings and Precautions (5.1)] Infections [see Warnings and Precautions (5.2)] Cytopenias [see Warnings and Precautions (5.3)] Atrial Fibrillation [see Warnings and Precautions (5.4)] Second Primary Malignancies [see Warnings and Precautions (5.5)] Tumor Lysis Syndrome [see Warnings and Precautions (5.6)] Because clinical trials are conducted under widely variable conditions, adverse event rates observed in clinical trials of a drug cannot be directly compared with rates of clinical trials of another drug and may not reflect the rates observed in practice. 6.1 Clinical Trials Experience Mantle Cell Lymphoma The data described below reflect exposure to IMBRUVICA in a clinical trial that included 111 patients with previously treated MCL treated with 560 mg daily with a median treatment duration of 8.3 months. The most commonly occurring adverse reactions (≥ 20%) were thrombocytopenia, diarrhea, neutropenia, anemia, fatigue, musculoskeletal pain, peripheral edema, upper respiratory tract infection, nausea, bruising, dyspnea, constipation, rash, abdominal pain, vomiting and decreased appetite (see Tables 1 and 2). The most common Grade 3 or 4 non-hematological adverse reactions (≥ 5%) were pneumonia, abdominal pain, atrial fibrillation, diarrhea, fatigue, and skin infections. Fatal and serious cases of renal failure have occurred with IMBRUVICA therapy. Increases in creatinine 1.5 to 3 times the upper limit of normal occurred in 9% of patients. Adverse reactions from the MCL trial (N=111) using single agent IMBRUVICA 560 mg daily occurring at a rate of ≥ 10% are presented in Table 1. Table 1: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with MCL (N=111)
Ten patients (9%) discontinued treatment due to adverse reactions in the trial (N=111). The most frequent adverse reaction leading to treatment discontinuation was subdural hematoma (1.8%). Adverse reactions leading to dose reduction occurred in 14% of patients. Patients with MCL who develop lymphocytosis greater than 400,000/mcL have developed intracranial hemorrhage, lethargy, gait instability, and headache. However, some of these cases were in the setting of disease progression. Forty percent of patients had elevated uric acid levels on study including 13% with values above 10 mg/dL. Adverse reaction of hyperuricemia was reported for 15% of patients. Chronic Lymphocytic Leukemia The data described below reflect exposure to IMBRUVICA in an open label clinical trial (Study 1) that included 48 patients with previously treated CLL and a randomized clinical trial (Study 2) that included 391 randomized patients with previously treated CLL or SLL. The most commonly occurring adverse reactions in Study 1 and Study 2 (≥ 20%) were thrombocytopenia, neutropenia, diarrhea, anemia, fatigue, musculoskeletal pain, upper respiratory tract infection, rash, nausea, and pyrexia. Approximately five percent of patients receiving IMBRUVICA in Study 1 and Study 2 discontinued treatment due to adverse events. These included infections, subdural hematomas and diarrhea. Adverse events leading to dose reduction occurred in approximately 6% of patients. Study 1 Adverse reactions and laboratory abnormalities from the CLL trial (N=48) using single agent IMBRUVICA 420 mg daily occurring at a rate of ≥ 10% are presented in Tables 3 and 4. Table 3: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with CLL (N=48) in Study 1
Table 4: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Patients with CLL (N=48) in Study 1
Study 2 Adverse reactions and laboratory abnormalities described below in Tables 5 and 6 reflect exposure to IMBRUVICA with a median duration of 8.6 months and exposure to ofatumumab with a median of 5.3 months in Study 2. Table 5: Non-Hematologic Adverse Reactions ≥ 10% Reported in Study 2
The system organ class and individual ADR terms are sorted in descending frequency order in the IMBRUVICA arm. * Includes multiple ADR terms Table 6: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Study 2
Based on laboratory measurements per IWCLL criteria Waldenström's Macroglobulinemia The data described below reflect exposure to IMBRUVICA in an open label clinical trial that included 63 patients with previously treated WM. The most commonly occurring adverse reactions in the WM trial (≥ 20%) were neutropenia, thrombocytopenia, diarrhea, rash, nausea, muscle spasms, and fatigue. Six percent of patients receiving IMBRUVICA in the WM trial discontinued treatment due to adverse events. Adverse events leading to dose reduction occurred in 11% of patients. Adverse reactions and laboratory abnormalities described below in Tables 7 and 8 reflect exposure to IMBRUVICA with a median duration of 11.7 months in the WM trial. Table 7: Non-Hematologic Adverse Reactions in ≥ 10% of Patients with Waldenström's Macroglobulinemia (N=63)
* Includes multiple ADR terms. Table 8: Treatment-Emergent* Decrease of Hemoglobin, Platelets, or Neutrophils in Patients with WM (N=63)
6. 2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of IMBRUVICA. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Hypersensitivity reactions including anaphylactic shock (fatal), urticaria, and angioedema have been reported. 7 DRUG INTERACTIONS Ibrutinib is primarily metabolized by cytochrome P450 enzyme 3A. 7.1 CYP3A Inhibitors In healthy volunteers, co-administration of ketoconazole, a strong CYP3A inhibitor, increased Cmax and AUC of ibrutinib by 29- and 24-fold, respectively. The highest ibrutinib dose evaluated in clinical trials was 12.5 mg/kg (actual doses of 840 – 1400 mg) given for 28 days with single dose AUC values of 1445 ± 869 ng ∙ hr/mL which is approximately 50% greater than steady state exposures seen at the highest indicated dose (560 mg). Avoid concomitant administration of IMBRUVICA with strong or moderate inhibitors of CYP3A. For strong CYP3A inhibitors used short-term (e.g., antifungals and antibiotics for 7 days or less, e.g., ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, telithromycin) consider interrupting IMBRUVICA therapy during the duration of inhibitor use. Avoid strong CYP3A inhibitors that are needed chronically. If a moderate CYP3A inhibitor must be used, reduce the IMBRUVICA dose. Patients taking concomitant strong or moderate CYP3A4 inhibitors should be monitored more closely for signs of IMBRUVICA toxicity [see Dosage and Administration (2.4)]. Avoid grapefruit and Seville oranges during IMBRUVICA treatment, as these contain moderate inhibitors of CYP3A [see Dosage and Administration (2.4), and Clinical Pharmacology (12.3)]. 7.2 CYP3A Inducers Administration of IMBRUVICA with rifampin, a strong CYP3A inducer, decreased ibrutinib Cmax and AUC by approximately 13- and 10-fold, respectively. Avoid concomitant use of strong CYP3A inducers (e.g., carbamazepine, rifampin, phenytoin and St. John's Wort). Consider alternative agents with less CYP3A induction [see Clinical Pharmacology (12.3)]. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy Pregnancy Category D [see Warnings and Precautions (5.7)]. Risk Summary Based on findings in animals, IMBRUVICA can cause fetal harm when administered to a pregnant woman. If IMBRUVICA is used during pregnancy or if the patient becomes pregnant while taking IMBRUVICA, the patient should be apprised of the potential hazard to the fetus. Animal Data Ibrutinib was administered orally to pregnant rats during the period of organogenesis at oral doses of 10, 40 and 80 mg/kg/day. Ibrutinib at a dose of 80 mg/kg/day was associated with visceral malformations (heart and major vessels) and increased post-implantation loss. The dose of 80 mg/kg/day in animals is approximately 14 times the exposure (AUC) in patients with MCL and 20 times the exposure in patients with CLL or WM administered the dose of 560 mg daily and 420 mg daily, respectively. Ibrutinib at doses of 40 mg/kg/day or greater was associated with decreased fetal weights. The dose of 40 mg/kg/day in animals is approximately 6 times the exposure (AUC) in patients with MCL administered the dose of 560 mg daily. 8.3 Nursing Mothers It is not known whether ibrutinib is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from IMBRUVICA, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of IMBRUVICA in pediatric patients has not been established. 8.5 Geriatric Use Of the 111 patients treated for MCL, 63% were 65 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse events (atrial fibrillation and hypertension), infections (pneumonia and cellulitis) and gastrointestinal events (diarrhea and dehydration) occurred more frequently among elderly patients. Of the 391 patients randomized in Study 2, 61% were ≥ 65 years of age. No overall differences in effectiveness were observed between age groups. Grade 3 or higher adverse events occurred more frequently among elderly patients treated with IMBRUVICA (61% of patients age ≥ 65 versus 51% of younger patients) [see Clinical Studies (14.2)]. Of the 63 patients treated for WM, 59% were 65 years of age or older. No overall differences in effectiveness were observed between these patients and younger patients. Cardiac adverse events (atrial fibrillation and hypertension), and infections (pneumonia and urinary tract infection) occurred more frequently among elderly patients. 8.6 Renal Impairment Less than 1% of ibrutinib is excreted renally. Ibrutinib exposure is not altered in patients with Creatinine clearance (CLcr) > 25 mL/min. There are no data in patients with severe renal impairment (CLcr < 25 mL/min) or patients on dialysis [see Clinical Pharmacology (12.3)]. 8.7 Hepatic Impairment Ibrutinib is metabolized in the liver. In a hepatic impairment study, data showed an increase in ibrutinib exposure. Following single dose administration, the AUC of ibrutinib increased 2.7-, 8.2- and 9.8-fold in subjects with mild (Child-Pugh class A), moderate (Child-Pugh class B), and severe (Child-Pugh class C) hepatic impairment compared to subjects with normal liver function. The safety of IMBRUVICA has not been evaluated in patients with hepatic impairment. Monitor patients for signs of IMBRUVICA toxicity and follow dose modification guidance as needed. It is not recommended to administer IMBRUVICA to patients with moderate or severe hepatic impairment (Child-Pugh classes B and C) [see Dosage and Administration (2.5) and Clinical Pharmacology (12.3)]. 8.8 Females and Males of Reproductive Potential Advise women to avoid becoming pregnant while taking IMBRUVICA because IMBRUVICA can cause fetal harm [see Use in Specific Populations (8.1)]. 8.9 Plasmapheresis Management of hyperviscosity in patients with WM may include plasmapheresis before and during treatment with IMBRUVICA. Modifications to IMBRUVICA dosing are not required. 11 DESCRIPTION Ibrutinib is an inhibitor of Bruton's tyrosine kinase (BTK). It is a white to off-white solid with the empirical formula C25H24N6O2 and a molecular weight 440.50. Ibrutinib is freely soluble in dimethyl sulfoxide, soluble in methanol and practically insoluble in water. The chemical name for ibrutinib is 1-[(3R)-3-[4-amino-3-(4-phenoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]-1-piperidinyl]-2-propen-1-one and has the following structure:
An Independent Review Committee (IRC) performed independent reading and interpretation of imaging scans. The IRC review demonstrated an ORR of 69%. The median time to response was 1.9 months. Lymphocytosis Upon initiation of IMBRUVICA, a temporary increase in lymphocyte counts (i.e., ≥ 50% increase from baseline and above absolute lymphocyte count of 5,000/mcL) occurred in 33% of patients in the MCL study. The onset of isolated lymphocytosis occurs during the first few weeks of IMBRUVICA therapy and resolves by a median of 8 weeks. 14.2 Chronic Lymphocytic Leukemia The safety and efficacy of IMBRUVICA in patients with CLL who have received at least one prior therapy were demonstrated in one uncontrolled trial and one randomized, controlled trial. Study 1 An open-label, multi-center trial was conducted in 48 previously treated CLL patients. The median age was 67 years (range, 37 to 82 years), 71% were male, and 94% were Caucasian. All patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 80 months and the median number of prior treatments was 4 (range, 1 to 12 treatments). At baseline, 46% of subjects had at least one tumor ≥ 5 cm. IMBRUVICA was administered orally at 420 mg once daily until disease progression or unacceptable toxicity. The ORR and DOR were assessed using a modified version of the International Workshop on CLL Criteria by an Independent Review Committee. The ORR was 58.3% (95% CI: 43.2%, 72.4%), all partial responses. None of the patients achieved a complete response. The DOR ranged from 5.6 to 24.2+ months. The median DOR was not reached. Study 2 A randomized, multicenter, open-label Phase 3 study of IMBRUVICA versus ofatumumab was conducted in patients with previously treated CLL or SLL. Patients (n=391) were randomized 1:1 to receive either IMBRUVICA 420 mg daily until disease progression, or unacceptable toxicity or ofatumumab at an initial dose of 300 mg, followed one week later by a dose of 2000 mg weekly for 7 doses and then every 4 weeks for 4 additional doses. Fifty seven patients randomized to ofatumumab crossed over following progression to receive IMBRUVICA. The median age was 67 years (range, 30 to 88 years), 68% were male, and 90% were Caucasian. All patients had a baseline ECOG performance status of 0 or 1. The trial enrolled 373 patients with CLL and 18 patients with SLL. The median time since diagnosis was 91 months and the median number of prior treatments was 2 (range, 1 to 13 treatments). At baseline, 58% of patients had at least one tumor ≥ 5 cm. Thirty-two percent of patients had 17p deletion. Progression free survival (PFS) as assessed by independent review committee (IRC) according to IWCLL criteria indicated a 78% statistically significant reduction in the risk of death or progression. Analysis of overall survival (OS) demonstrated a 57% statistically significant reduction in the risk of death for patients in the IMBRUVICA arm. Efficacy results for Study 2 are shown in Table 10 and the Kaplan-Meier curves for PFS and OS are shown in Figures 1 and 2, respectively. Table 10: Efficacy Results in Study 2
Median OS not reached for either arm IRC evaluated. All partial responses achieved; none of the patients achieved a complete response Figure 1: Kaplan-Meier Curve of Progression-Free Survival (ITT Population) in Study
Figure 2: Kaplan-Meier Curve of Overall Survival (ITT Population) in Study 2
IRC evaluated. All partial responses achieved; none of the patients achieved a complete response. Lymphocytosis Upon initiation of IMBRUVICA, an increase in lymphocyte counts (i.e., ≥ 50% increase from baseline and above absolute lymphocyte count of 5,000/mcL) occurred in 77% of patients in the CLL study. The onset of isolated lymphocytosis occurs during the first month of IMBRUVICA therapy and resolves by a median of 23 weeks (range 1 – 104+ weeks). 14.3 Waldenström's Macroglobulinemia The safety and efficacy of IMBRUVICA in WM were evaluated in an open-label, multi-center, single-arm trial of 63 previously treated patients. The median age was 63 years (range, 44 to 86 years), 76% were male, and 95% were Caucasian. All patients had a baseline ECOG performance status of 0 or 1. The median time since diagnosis was 74 months, and the median number of prior treatments was 2 (range, 1 to 11 treatments). At baseline, the median serm IgM value was 3.5 g/dL (range, 0.7 to 8.4 g/dL). IMBRUVICA was administered orally at 420 mg once daily until disease progression or unacceptable toxicity. The responses were assessed by investigators and an Independent Review Committee (IRC) using criteria adopted from the International Workshop of Waldenström's Macroglobulinemia. Responses, defined as partial response or better, per IRC are shown in Table 12. Table 12: Response Rate and Duration of Response Based on IRC Assessment in Patients with WM
The median time to response was 1.2 months (range: 0.7–13.4 months). 16 HOW SUPPLIED/STORAGE AND HANDLING The white opaque 140 mg capsules marked with "ibr 140 mg" in black ink are available in white HDPE bottles with a child-resistant closure: 90 capsules per bottle: NDC 57962-140-09 120 capsules per bottle: NDC 57962-140-12 Store bottles at room temperature 20°C to 25°C (68°F to 77°F). Excursions are permitted between 15°C and 30°C (59°F to 86°F). Retain in original package until dispensing. 17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling (Patient Information). Hemorrhage: Inform patients of the possibility of bleeding, and to report any signs or symptoms (blood in stools or urine, prolonged or uncontrolled bleeding). Inform the patient that IMBRUVICA may need to be interrupted for medical or dental procedures [see Warnings and Precautions (5.1)]. Infections: Inform patients of the possibility of serious infection, and to report any signs or symptoms (fever, chills, weakness, confusion) suggestive of infection [see Warnings and Precautions (5.2)]. Atrial Fibrillation: Counsel patients to report any signs of palpitations, lightheadedness, dizziness, fainting, shortness of breath, and chest discomfort [see Warnings and Precautions (5.4)]. Second primary malignancies: Inform patients that other malignancies have occurred in patients who have been treated with IMBRUVICA, including skin cancers and other carcinomas [see Warnings and Precautions (5.5)]. Tumor lysis syndrome: Inform patients of the potential risk of tumor lysis syndrome and report any signs and symptoms associated with this event to their healthcare provider for evaluation [see Warnings and Precautions (5.6)]. Embryo-fetal toxicity: Advise women of the potential hazard to a fetus and to avoid becoming pregnant [see Warnings and Precautions (5.7)]. Inform patients to take IMBRUVICA orally once daily according to their physician's instructions and that the capsules should be swallowed whole with a glass of water without being opened, broken, or chewed at approximately the same time each day [see Dosage and Administration (2.1)]. Advise patients that in the event of a missed daily dose of IMBRUVICA, it should be taken as soon as possible on the same day with a return to the normal schedule the following day. Patients should not take extra capsules to make up the missed dose [see Dosage and Administration (2.5)]. Advise patients of the common side effects associated with IMBRUVICA [see Adverse Reactions (6)]. Direct the patient to a complete list of adverse drug reactions in PATIENT INFORMATION. Advise patients to inform their health care providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7)]. Advise patients that they may experience loose stools or diarrhea, and should contact their doctor if their diarrhea persists. Advise patients to maintain adequate hydration. http://www.medicines.org.uk/emc/medicine/29383 http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=0dfd0279-ff17-4ea9-89be-9803c71bab44 强生抗癌药Imbruvica在欧盟获批上市 Ibrutinib单药治疗对套细胞性淋巴瘤（MCL）或弥漫性大B细胞性淋巴瘤（DLBCL）患者有效 Pharmacyclics生物制药公司（纳斯达克：PCYC）今日宣布2项单独的II期临床实验显示口服ibrutinib单药治疗复发/难治性MCL或DLBCL患者有效。Ibrutinib是一种实验性布鲁顿酪氨酸激酶（Bruton‘s Tyrosine Kinase， BTK）抑制剂。 Pharmacyclics公司资助了这两项研究，并与扬森研发责任有限公司共同开发了这个药物。研究数据近期在瑞典斯德哥尔摩举办的第18届欧洲血液病协会（EHA）年会上公布。 研究者在去年12月美国血液病协会大会上也报告了一部分MCL和DLBCL患者的研究数据，而今年EHA会议上呈现的结果是对原有数据的进一步扩充。Ibrutinib治疗复发/难治性MCL患者的关键结果如下： 总体缓解率（ORR）为68%，其中21%为完全缓解（CR），即所有肿瘤征象均消失；47%为部分缓解（PR）。 所有获得缓解的患者中，中位缓解期（DOR）的估计值为17.5个月；中位无进展生存（PFS）为13.9个月；中位总生存（OS）尚未到达，但估计58%在18个月。 20%以上的患者报告了治疗期间的紧急不良事件（AEs），包括腹泻（50%），虚弱（41%），恶心（31%），周围性水肿（28%），呼吸困难（27%），便秘（25%），上呼吸道感染（23%），呕吐（23%）和食欲减退（21%），这些反应与上次报道的数据相同。仅8例患者因不良事件终止治疗。 英国普利茅斯Derriford医院血液病科的顾问血液病学家Simon Rule教授在EHA大会上展示了该研究的结果，他表示，MCL患者在接受单药治疗的情况下能取得这样的成果意义非凡，并意味着这种疗法前景广阔。而缓解率随时间的推移仍在继续增长，且没有新的安全警告出现，这样的事实格外使人欣慰。 另一项研究针对复发/难治性DLBCL患者，研究者评价了ibrutinib用于DLBCL的活化B细胞样（ABC）亚型是否比用于生发中心B细胞样（GCB）亚型更有效。DLBCL的ABC亚型依赖于B细胞抗原受体（BCR）通路，而BTK是其中的关键元素。 Ibrutinib能选择性抑制BTK，从而抑制恶性B细胞的生长和增殖。该项研究的主要结果如下： 1.单药治疗时，ABC亚型的患者与GCB亚型的患者相比，显示了对ibrutinib优先响应（ORR分别为41%和5%，Fisher精确检验） 2.ABC亚型和GCB亚型患者的中位OS分别为9.7个月和3.35个月。 3.70例患者的安全性数据未显示新的安全警告。3%以上的患者出现了3级以上的AEs，包括虚弱（9%）,低钠血症（9%），肺炎（7%），脱水（4%）和胸膜渗出（4%）。 美国洛杉矶UCLA医学中心内科副教授Even de Vos作为研究者在EHA大会上汇报这些结果时表示，这些结果显示ibrutinib单药治疗对一部分参与实验的ABC亚型的DLBCL患者有效。由于ABC亚型的DLBCL患者难以治疗，这些结果展示了良好的前景。 ------------------------------------------------- 产地国家: 美国 原产地英文商品名: IMBRUVICA 140mg/capsules 90capsules 原产地英文药品名: ibrutinib 中文参考商品译名: IMBRUVICA 140毫克/胶囊 90胶囊/瓶 中文参考药品译名: 依鲁替尼 生产厂家中文参考译名: Pharmacyclics/Janssen Biotech Inc. 生产厂家英文名: Pharmacyclics/Janssen Biotech Inc. ----------------------------------------------------- 产地国家: 美国 原产地英文商品名: IMBRUVICA 140mg/capsules 120capsules 原产地英文药品名: ibrutinib 中文参考商品译名: IMBRUVICA 140毫克/胶囊 120胶囊/瓶 中文参考药品译名: 依鲁替尼 生产厂家中文参考译名: Pharmacyclics/Janssen Biotech Inc. 生产厂家英文名: Pharmacyclics/Janssen Biotech Inc. ------------------------------------------------- 产地国家: 德国 原产地英文商品名: IMBRUVICA hard capsules 140mg/capsules 90capsules 原产地英文药品名: ibrutinib 中文参考商品译名: IMBRUVICA 140毫克 90胶囊/瓶 中文参考药品译名: 依鲁替尼 生产厂家中文参考译名: Pharmacyclics/Janssen Biotech Inc. 生产厂家英文名: Pharmacyclics/Janssen Biotech Inc. ----------------------------------------------------- 产地国家: 德国 原产地英文商品名: IMBRUVICA hard capsules 140mg/capsules 120capsules 原产地英文药品名: ibrutinib 中文参考商品译名: IMBRUVICA 140毫克 120胶囊/瓶 中文参考药品译名: 依鲁替尼 生产厂家中文参考译名: Pharmacyclics/Janssen Biotech Inc. 生产厂家英文名: Pharmacyclics/Janssen Biotech Inc. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
