Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma.
Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma.
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DOI：
10.1001/jamaoncol.2015.2010
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发表时间：
2015-09
期刊：
影响因子：
28.4
通讯作者：
Landgren O
中科院分区：
文献类型：
--
作者：
Korde N;Roschewski M;Zingone A;Kwok M;Manasanch EE;Bhutani M;Tageja N;Kazandjian D;Mailankody S;Wu P;Morrison C;Costello R;Zhang Y;Burton D;Mulquin M;Zuchlinski D;Lamping L;Carpenter A;Wall Y;Carter G;Cunningham SC;Gounden V;Sissung TM;Peer C;Maric I;Calvo KR;Braylan R;Yuan C;Stetler-Stevenson M;Arthur DC;Kong KA;Weng L;Faham M;Lindenberg L;Kurdziel K;Choyke P;Steinberg SM;Figg W;Landgren O
Carfilzomib-来那度胺-地塞米松治疗在新诊断的多发性骨髓瘤（NDMM）患者中产生深度反应。重要的是要了解这种组合的耐受性和对微小残留病（MRD）阴性的影响，因为这个终点与生存率的提高有关。评估卡非佐米-来那度胺-地塞米松治疗NDMM和高危郁积型多发性骨髓瘤（SMM）的安全性和疗效。美国国立卫生研究院临床中心的临床和相关初步研究。NDMM或高风险SMM患者在2011年7月11日至2013年10月9日期间入组。中位随访时间为17.3个月（NDMM）和15.9个月（SMM）。8个28天周期包括第1、2、8、9、15和16天卡非佐米20/36 mg/m2;第1 - 21天来那度胺25 mg;第1、2、8、9、15、16、22和23天地塞米松20/10 mg（周期1-4/5-8）。至少达到疾病稳定的患者随后接受24个周期的来那度胺延长给药。主要终点为3级或以上神经病变（NDMM）和至少非常好的部分缓解率（SMM）。还评估了微小残留病变。在45例NDMM患者中，没有3级或以上的神经病变。在12例高风险SMM患者中，最常见的任何级别不良事件为淋巴细胞减少症（12例[100%]）和胃肠道疾病（11例[92%]）。在研究期间，所有SMM患者均至少获得了非常好的部分缓解。在28名NDMM患者和12名SMM患者中，至少达到接近完全缓解，28名患者中有28名MRD阴性（100% [95% CI，88%-100%]），11/12（92% [95% CI，62%-100%]）（多参数流式细胞术），21例中的14例（67% [95% CI，43%-85%]）和12例中的9例（75% [95% CI，43%-94%]）（下一代测序）。在NDMM患者中，通过流式细胞术和下一代测序，MRD阴性与MRD阳性状态的12个月无进展生存率分别为100%与79%（95% CI，47%-94%; P <0.001）和100%与95%（95% CI，75%-99%; P = 0.02）。Carfilzomib-来那度胺-地塞米松治疗是可耐受的，并且在NDMM中显示出较高的MRD阴性率，这转化为MRD阴性患者的无进展生存期更长。卡非佐米-来那度胺-地塞米松治疗也证明了在高风险SMM中的疗效。
Carfilzomib-lenalidomide-dexamethasone therapy yields deep responses in patients with newly diagnosed multiple myeloma (NDMM). It is important to gain an understanding of this combination’s tolerability and impact on minimal residual disease (MRD) negativity because this end point has been associated with improved survival. To assess the safety and efficacy of carfilzomib-lenalidomide-dexamethasone therapy in NDMM and high-risk smoldering multiple myeloma (SMM). Clinical and correlative pilot study at the National Institutes of Health Clinical Center. Patients with NDMM or high-risk SMM were enrolled between July 11, 2011, and October 9, 2013. Median follow-up was 17.3 (NDMM) and 15.9 months (SMM). Eight 28-day cycles were composed of carfilzomib 20/36 mg/m2 on days 1, 2, 8, 9, 15, and 16; lenalidomide 25 mg on days 1 through 21; and dexamethasone 20/10 mg (cycles 1-4/5-8) on days 1, 2, 8, 9, 15, 16, 22, and 23. Patients who achieved at least stable disease subsequently received 24 cycles of lenalidomide extended dosing. Primary end points were neuropathy of grade 3 or greater (NDMM) and at least very good partial response rates (SMM). Minimal residual disease was also assessed. Of 45 patients with NDMM, none had neuropathy of grade 3 or greater. Of 12 patients with high-risk SMM, the most common of any-grade adverse events were lymphopenia (12 [100%]) and gastrointestinal disorders (11 [92%]). All patients with SMM achieved at least a very good partial response during the study period. Among the 28 patients with NDMM and the 12 with SMM achieving at least a near-complete response, MRD negativity was found in 28 of 28 (100% [95% CI, 88%-100%]), 11 of 12 (92% [95% CI, 62%-100%]) (multiparametric flow cytometry), 14 of 21 (67% [95% CI, 43%-85%]), and 9 of 12 (75% [95% CI, 43%-94%]) (next-generation sequencing), respectively. In patients with NDMM, 12-month progression-free survival for MRD-negative vs MRD-positive status by flow cytometry and next-generation sequencing was 100% vs 79% (95% CI, 47%-94%; P < .001) and 100% vs 95% (95% CI, 75%-99%; P = .02), respectively. Carfilzomib-lenalidomide-dexamethasone therapy is tolerable and demonstrates high rates of MRD negativity in NDMM, translating into longer progression-free survival in patients achieving MRD negativity. Carfilzomib-lenalidomide-dexamethasone therapy also demonstrates efficacy in high-risk SMM.
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