新型抗癌药：Pepaxto（melphalan flufenamide）美法仑氟苯酰胺，也称为美氟芬 是一款首创（first-in-class）的肽偶联药物，它将烷化剂与靶向氨肽酶的多肽偶联在一起。
近日，美国食品药品监督管理局（FDA）已批准PEPAXTO（melphalan flufenamide，中文译名：美法仑氟苯甲酰胺）冻干粉注射剂，与地塞米松联用，用于治疗复发或难治性多发性骨髓瘤患者，这些患者先前已接受了至少四项先前疗法，包括蛋白酶体抑制剂、免疫调节剂、靶向CD38的单克隆抗体。
PEPAXTO是一款抗癌肽-药物偶联物（PDC），其靶向氨基肽酶并将烷基化剂迅速释放到肿瘤细胞中，PEPAXTO是第一种被FDA批准用于多发性骨髓瘤的抗癌肽-药物偶联物。
批准日期：2021年2月26日  公司：Oncopeptides Inc
PEPAXTO（美法仑氟苯甲酰胺[melphalan flufenamide]）注射用，静脉内使用
美国初次批准：2021年
作用机理
美法仑氟苯酰胺是肽缀合的烷基化药物。由于其亲脂性，美法仑氟苯酰胺被被动地分布到细胞中，然后被酶水解为美法仑。与其他氮芥类药物相似，DNA的交联涉及美法仑氟苯酰胺的抗肿瘤活性。 在细胞测定中，美法仑氟苯酰胺抑制了造血和实体肿瘤细胞的增殖并诱导了其凋亡。此外，美法仑氟苯甲酰胺在耐美法仑和不耐药的多发性骨髓瘤细胞系中与地塞米松具有协同的细胞毒性作用。
适应症和用途
PEPAXTO是一种烷基化药物，与地塞米松联合使用，可用于治疗已接受至少四项既往疗法且其疾病至少对一种蛋白酶体抑制剂，一种免疫调节剂和一种CD38定向单克隆抗体难治的复发或难治性多发性骨髓瘤的成年患者抗体。
该指示根据响应率在加速批准下得到批准。对于该适应症的持续批准可能取决于对临床获益的确证性试验的验证和描述。
使用限制：未标明PEPAXTO，不建议将其用作对照临床试验以外的移植条件疗法。
剂量和给药
PEPAXTO的推荐剂量是在每个28天治疗周期的第1天的30分钟内静脉注射40mg，并与地塞米松联用。
有关准备和管理的说明，请参阅“完整处方信息”。
剂量形式和强度
注射用：20mg美法仑氟苯酰胺为冻干粉单剂量小瓶，用于重组和稀释。
禁忌症
对美法仑氟苯酰胺或美法仑发生严重超敏反应的历史。
警告和注意事项
血小板减少症：在基线，治疗期间和临床指示时监测血小板计数。可能需要延迟剂量或减少剂量以恢复血小板。
中性粒细胞减少症：监测基线，治疗期间和临床指示的中性粒细胞计数。监测中性粒细胞减少症患者的感染迹象。可能需要延迟剂量或减少剂量才能允许中性粒细胞的恢复。
贫血：在基线，治疗期间和临床指示时监测红细胞计数。
感染：监测感染的体征/症状并及时治疗。
剂量高于推荐剂量的PEPAXTO导致死亡的风险增加：超过推荐剂量的PEPAXTO剂量可能与死亡率有关。
继发性恶性肿瘤：长期监测患者继发性恶性肿瘤的发展。
胚胎-胎儿毒性：可引起胎儿伤害。建议具有生殖风险的患者对胎儿和使用有效避孕有潜在风险。
不良反应
最常见的不良反应（>20％）是疲劳，恶心，腹泻，发热和呼吸道感染。
最常见的实验室异常（≥50％）是白细胞减少，血小板减少，淋巴细胞减少，中性粒细胞减少，血红蛋白减少和肌酐增加。
要报告可疑的不良反应，请致电1-866-522-8894联系Oncopeptides Inc，或致电1-800-FDA-1088与FDA联系或访问www.fda.gov/medwatch。
在特定人群中的使用
哺乳期：建议不要母乳喂养。
包装供应/存储和处理方式
供应方式
PEPAXTO是白色至灰白色的冻干粉，用于复溶（复溶后溶液澄清，无色至浅黄色），装在50mL单剂量小瓶中，该小瓶中含20mg甲氧氟苯氟胺。每个20毫克的小瓶包装在一个纸箱中（NDC 73657-020-01）。
样品瓶塞不是用天然橡胶胶乳制造的。
贮存
冷藏时应存放在2°C至8°C（36°F至46°F）的环境中，并避光。 保留在原始纸箱中，直到使用。
处理与处置
PEPAXTO是一种有害药物。请遵循特殊的处理和处置程序。
所有已用于的材料
稀释和给药，包括在30分钟之前制成的任何复溶溶液，应按照危险药物的标准程序进行处理。
完整说明资料附件：
https://pepaxto.com/docs/pepaxto_pi.pdf
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FDA Approves Oncopeptides´ PEPAXTO(melphalan flufenamide)for Patients with Triple-Class Refractory Multiple Myeloma
U.S. Food and Drug Administration(FDA) has approved PEPAXTO(melphalan flufenamide), known during clinical development as melflufen, in combination with dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. This indication has been granted under accelerated approval based upon the HORIZON trial. PEPAXTO is the first anticancer peptide-drug conjugate approved in multiple myeloma.
About PEPAXTO
PEPAXTO(melphalan flufenamide)is the first anticancer peptide-drug conjugate for patients with triple-class refractory Multiple Myeloma who have received at least four prior lines of therapy. PEPAXTO uses innovative technology that links a peptide carrier to a cytotoxic agent, resulting in a lipophilic compound. Due to its lipophilicity, PEPAXTO is distributed into cells.  PEPAXTO is designed to leverage aminopeptidases, which are overexpressed in multiple myeloma cells and cause the release of the cytotoxic agents. PEPAXTO is administered as a once monthly thirty-minute infusion.
INDICATION
PEPAXTO is indicated in combination with dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy and whose disease is refractory to at least one proteasome inhibitor, one immunomodulatory agent, and one CD38-directed monoclonal antibody. This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Limitation of Use
PEPAXTO is not indicated and is not recommended for use as a conditioning regimen for transplant outside of controlled clinical trials.
IMPORTANT SAFETY INFORMATION
PEPAXTO is contraindicated in patients with a history of serious allergic reaction to melphalan flufenamide or melphalan.
PEPAXTO may cause thrombocytopenia, which may lead to hemorrhage.Monitor platelets at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first 2 months of treatment with PEPAXTO. Do not administer PEPAXTO if the platelet count is less than 50 x 109/L. Withhold PEPAXTO until platelet count is 50 x 109/L or greater and resume at same or reduced dose based on duration of interruption. Adjust dose and/or dose schedule based on signs and symptoms of bleeding.
PEPAXTO may cause neutropenia, which may lead to infection. Monitor neutrophil counts at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first 2 months of treatment with PEPAXTO. Do not administer PEPAXTO if absolute neutrophil count is less than 1 x 109/L. Withhold PEPAXTO until absolute neutrophil count is 1 x 109/L or greater and resume at same or reduced dose based on duration of interruption. Consider leukocyte growth factor as clinically appropriate.
PEPAXTO may cause anemia. Monitor red blood cell counts at baseline, during treatment, and as clinically indicated. Monitor more frequently during the first 2 months of treatment with PEPAXTO. Treat anemia as clinically indicated. Dosage modification and dose delay of PEPAXTO may be required to allow for recovery of red blood cells.
Patients taking PEPAXTO experienced infections, including fatal infections. Consider antimicrobials as clinically appropriate.
Nonclinical safety studies with melphalan flufenamide at dosages exceeding the recommended dose for PEPAXTO were associated with mortality. The safety and efficacy of PEPAXTO has not been established for use as a conditioning regimen in patients receiving transplant.
Secondary malignancies such as myelodysplastic syndromes or acute leukemia have been reported in patients with multiple myeloma who were treated with PEPAXTO. Monitor patients long term for the development of secondary malignancies.
Based on its mechanism of action, PEPAXTO can cause fetal harm when administered to a pregnant woman because it is genotoxic and targets actively dividing cells. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with PEPAXTO and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEPAXTO and for 3 months after the last dose.
The most common adverse reactions (≥20%; Grade 1-4)were fatigue (55%), nausea (32%), diarrhea (27%), pyrexia(24%), and respiratory tract infection (24%).