【资讯翻译】FDA批准雷那度胺用作MM自体移植后的维持治疗..._胺_其他_生化试剂_知道

FDA Approves Lenalidomide as Maintenance Therapy for Patients With Multiple Myeloma Following Autologous Stem Cell Transplant

FDA批准来那度胺用于自体干细胞移植后多发性骨髓瘤患者的维持治疗

On February 22, theU.S. Food and Drug Administration(FDA) expanded the existing indication for lenalidomide (Revlimid) 10 mg capsules to include use for patients with multiple myeloma as maintenance therapy following autologous hematopoietic stem cell transplant. The expanded indication makes lenalidomide the first and only treatment to receive FDA approval for maintenance use following autologous hematopoietic stem cell transplant.

2月22日，美国食品和药物管理局（FDA）将来那度胺（Revlimid）10mg胶囊的现有适应征扩大，包括用来维持治疗自体干细胞移植患者出现的多发性骨髓瘤。来那度胺适应症扩展后，成为FDA批准的第一个也是唯一的用于自体造血干细胞移植后维持治疗的药物。

“Autologous stem cell transplant after induction therapy is part of the continuum of care for transplant-eligible [patients with] multiple myeloma. However, most patients will still see their disease recur or progress after this treatment,” saidPhilip McCarthy, MD, Director, Blood and Marrow Transplant Center, Department of Medicine atRoswell Park Cancer Institute.“Lenalidomide maintenance therapy, which has been shown to increase progression-free survival following autologous stem cell transplant in clinical trials,can be considered a standard of care for these patients.”

“诱导治疗后的自体干细胞移植是符合移植的[多发性骨髓瘤患者]的连续照护的一部分。然而，大多数患者治疗后仍然会出现疾病的复发或进展，”罗斯威尔公园癌症研究所（Roswell Park Cancer Institute）医学部血液和骨髓移植中心主任Philip McCarthy博士说。 “临床试验已显示自体干细胞移植后使用来那度胺维持治疗可增加无进展生存期，可作为此类患者的标准治疗方案。

Clinical Trial Findings

临床试验结果

The approval was based on two large studies—CALGB 100104andIFM 2005-02—including more than 1,000 patients comparing lenalidomide maintenance therapy given until disease progression or unacceptable toxicity afterautologous hematopoietic stem cell transplant vs no maintenance. In both studies, the primary efficacy endpoint was progression-free survival.

基于两项大规模的研究--CALGB 100104和IFM 2005-02—涉及1000多名患者，比较疾病进展发生或自体造血干细胞移植后出现无法接受的毒性时给予来那度胺维持治疗和不维持治疗两种方案。在两项研究中，主要功效评估指标是无进展生存期。

In the most current progression-free survival analysis, Study 1 (CALGB 100104) demonstrated a median progression-free survival of 5.7 years (95% confidence interval [CI] = 4.4–not estimable) vs 1.9 years (95% CI = 1.6–2.5) for no maintenance, a difference of 3.8 years (hazard ratio [HR] = 0.38; 95% CI = 0.28–0.50).

最新的无进展生存期分析：研究1（CALGB 100104）的中位无进展生存期为5.7年（95％置信区间[CI] = 4.4-不可估计），而无维持治疗为1.9年（95％CI = 1.6–2.5），相差3.8年（风险比[HR] = 0.38; 95％CI = 0.28-0.50）。

Study 2 (IFM 2005-02) also showed a benefit with a median progression-free survival of 3.9 years (95% CI = 3.3–4.7) vs 2 years (95% CI =1.8–2.3) for no maintenance, a difference of 1.9 years (HR = 0.53; 95% CI = 0.44–0.64).

研究2（IFM 2005-02）的中位无进展生存期为3.9年（95％CI = 3.3-4.7），而无维持治疗为2年（95％CI = 1.8-2.3），相差 1.9年（HR = 0.53; 95％CI = 0.44-0.64）。

Individual studies were not powered for an overall survival endpoint.

个别的研究不足以分析总生存评估指标。

A descriptive analysis showed the median overall survival in Study 1 was 9.3 years (95% CI = 8.5–not estimable) for patients who received lenalidomide vs 7 years (95% CI = 5.9–8.6) for no maintenance (HR = 0.59; 95% CI = 0.4–0.78). In Study 2, median overall survival was 8.8 years (95% CI = 7.4–not estimable) for patients who received lenalidomide vs 7.3 years (95% CI = 6.7–9.0) for no maintenance (HR = 0.90; 95% CI = 0.72–1.13).

一项描述性分析显示，研究1中使用来那度胺的患者的中位总生存期为9.3年（95％CI = 8.5-不可估计），而无维持治疗的患者（HR = 0.59; 95 ％CI = 0.4-0.78）的中位总生存期为7年（95％CI = 5.9-8.6）。研究2中使用来那度胺的患者的中位总生存期为8.8年（95％CI = 7.4-不可估计），而无维持治疗（HR = 0.90; 95％CI = 0.72 -1.13）的中位总生存期为7.3年（95％CI = 6.7-9.0）。

Adverse Events

不良事件

The most frequently reported adverse reactions in ≥ 20% (lenalidomide arm) across both maintenance studies (Study 1, Study 2 respectively) were neutropenia (79%, 61%); thrombocytopenia (72%, 24%); leukopenia (23%, 32%); anemia (21%, 9%); upper respiratory tract infection (27%, 11%); bronchitis (5%, 47%); nasopharyngitis (2%, 35%); cough (10%, 27%); gastroenteritis (0%, 23%); diarrhea (55%, 39%); rash (32%, 8%); fatigue (23%, 11%); asthenia (0%, 30%); muscle spasm (0%, 33%); and pyrexia (8%, 21%). The most frequently reported Grade 3 or 4 reactions (more than 20% in the lenalidomide arm) included neutropenia, thrombocytopenia, and leukopenia.

两个维持治疗的研究（研究1，研究2）中≥20％（来那度胺组）常报告的不良反应是中性粒细胞减少症（79％，61％）; 血小板减少（72％，24％）; 白细胞减少（23％，32％）; 贫血（21％，9％）; 上呼吸道感染（27％，11％）; 支气管炎（5％，47％）; 鼻咽炎（2％，35％）; 咳嗽（10％，27％）; 胃肠炎（0％，23％）; 腹泻（55％，39％）; 皮疹（32％，8％）; 疲劳（23％，11％）; 虚弱（0％，30％）; 肌肉痉挛（0％，33％）; 和发热（8％，21％）。常报告的3或4级反应（来那度胺组20％以上）包括中性粒细胞减少症，血小板减少和白细胞减少。

The frequencies of onset of adverse reactions were generally highest in the first 6 months of treatment and then the frequencies decreased over time or remained stable throughout treatment.

不良反应发生的频率通常在治疗的前6个月最高，然后随着时间降低或在整个治疗中保持稳定。

In patients receiving lenalidomide maintenance therapy, hematologic second primary malignancies occurred in 7.5% of patients compared to 3.3% in patients receiving placebo. The incidence of hematologic plus solid tumor (excluding squamous cell carcinoma and basal cell carcinoma) second primary malignancies was 14.9%, compared to 8.8% in patients receiving placebo with a median follow-up of 91.5 months. Nonmelanoma skin cancer second primary malignancies, including squamous cell carcinoma and basal cell carcinoma, occurred in 3.9% of patients receiving lenalidomide maintenance, compared to 2.6% in the placebo arm.

接受来那度胺维持治疗的患者中，有7.5％出现了血液第二原发性恶性肿瘤，而接受安慰剂的患者中有3.3％。血液+实体瘤（不包括鳞状细胞癌和基底细胞癌）第二原发性恶性肿瘤的发生率为14.9％，相比之下，接受安慰剂的患者的发生率为8.8％，中位随访91.5个月。非黑色素瘤皮肤癌第二原发性恶性肿瘤（包括鳞状细胞癌和基底细胞癌）在接受来那度胺维持治疗的患者中发生率为3.9％，而安慰剂组中为2.6％。

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【资讯翻译】FDA批准雷那度胺用作MM自体移植后的维持治疗...