近日，美国FDA批准了来那度胺作为多发性骨髓瘤自体造血干细胞移植后的维持治疗。
获批证据
该项批准基于两项研究（CALGB 100104和IFM 2005-02），共纳入1000多例MM患者。ASCT后，患者分别接受了来那度胺或安慰剂维持治疗，主要终点是PFS。
在CALGB 100104研究中，来那度胺组的中位PFS为5.7年，而安慰剂组为1.9年，风险比（HR）为0.38。
在IFM 2005-02研究中，来那度胺组的中位PFS为3.9年，安慰剂组为2年，HR为0.53。这两项研究未评估总生存期。
据报道，来那度胺治疗组中最常见的不良反应（每个研究均超过20%）有血小板减少、白细胞减少、中性粒细胞减少、贫血、腹泻、胃肠炎、支气管炎、咽炎、上呼吸道感染、咳嗽、皮疹、乏力、肌肉痉挛、发热和疲劳等。治疗前6个月的不良反应发生率最高。
最常见的3/4不良反应（超过于20%）有血小板减少、白细胞减少和中性粒细胞减少。
另外，第二原发性恶性肿瘤在来那度胺组中更频发（7.5% vs 3.3%）；把实体瘤包含在内时，来那度胺组的第二原发癌发生率为14.9% vs 8.8%，非黑色素瘤皮肤癌也较高（3.9% vs 2.6%）。
药物总结
来那度胺（lenalidomide）
靶点：
作用靶点尚未阐明，已知包括抗肿瘤、抗血管生成、促红细胞生成和免疫调节特性。
获批适应症：
1、多发性骨髓瘤：合用地塞米松治疗先前至少接受过1种疗法的患者。 2、骨髓异常综合症：用于治疗伴５q缺失的骨髓增生异常综合征所致的输血依赖性再生障碍性贫血患者。
不良反应：
最常见的不良反应为疲乏、中性粒细胞减少、便秘、腹泻等，严重不良反应包括血液学方面的毒性反应（如中性粒细胞减少症和血小板减少症）；深部静脉血栓形成和肺动脉栓塞。
注意事项：
孕妇禁用。所有服用的女性需进行严格的避孕。
用法用量：
推荐起始剂量为25 mg，每日口服25 mg，28天为1个周期，口服直至疾病进展；与地塞米松合用时，推荐剂量为在第1、8、15和22天口服40 mg地塞米松（28天为1个周期）。
FDA Approves Maintenance Lenalidomide for Multiple Myeloma
The US Food and Drug Administration (FDA) has expanded the approval of lenalidomide (Revlimid) to include its use as maintenance therapy for patients with multiple myeloma following autologous stem cell transplant (ASCT).
“ASCT after induction therapy is part of the continuum of care for transplant-eligible multiple myeloma patients. However, most patients will still see their disease recur or progress after this treatment,” said Philip McCarthy, MD, director of the Blood and Marrow Transplant Center at Roswell Park Cancer Institute in Buffalo, in a press release. “Lenalidomide maintenance therapy, which has been shown to increase progression-free survival (PFS) following ASCT in clinical trials can be considered a standard of care for these patients.”
The expanded approval was based on a pair of studies (CALGB 100104 and IFM 2005-02) that together included over 1,000 patients. Following ASCT, the studies compared maintenance therapy with lenalidomide vs placebo, with PFS as the primary endpoint.
In CALGB 100104, the median PFS in patients who received maintenance therapy was 5.7 years vs 1.9 years with placebo, for a hazard ratio (HR) of 0.38 (95% CI, 0.28–0.50).
In IFM 2005-02, a European-based study, lenalidomide maintenance yielded a median PFS of 3.9 years vs 2 years with placebo, for an HR of 0.53 (95% CI, 0.44–0.64). The studies were not powered to measure overall survival.
The most frequently reported adverse events (20% or higher in either trial) among patients receiving lenalidomide were thrombocytopenia, leukopenia, neutropenia, anemia, diarrhea, gastroenteritis, bronchitis, nasopharyngitis, upper respiratory tract infection, cough, rash, asthenia, muscle spasm, pyrexia, and fatigue. Onset of adverse events was generally highest in the first 6 months of treatment.
The most frequently reported grade 3/4 events (greater than 20%) were thrombocytopenia, leukopenia, and neutropenia.
Second primary malignancies were also more frequent in patients receiving lenalidomide maintenance (7.5% had second hematologic cancers vs 3.3% with placebo). When including solid tumors, the incidence rate of second primary cancers was 14.9% among patients receiving lenalidomide vs 8.8% among those receiving placebo. Non-melanoma skin cancers were also higher (3.9% vs 2.6%).
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参考文献
FDA Approves Maintenance Lenalidomide for Multiple Myeloma.Madscape.2017
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