KTd 和 ASCT 对功能性高危多发性骨髓瘤的反应适应性挽救——澳大利亚白血病和淋巴瘤组 (ALLG) MM17实验
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/RgoDMXJyUwawntkV9l2Rwae08kLNWA8jTExFMILOAuuO2IGzzhlNqqOkdib3HPA1w3HSFmNiaoq4a2ll7xNXzibHg/640?wx_fmt=jpeg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Response adaptive salvage with KTd and ASCT for functional high-risk multiple myeloma—The Australasian Leukemia and Lymphoma Group (ALLG) MM17 Trial</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">KTd 和 ASCT 对功能性高危多发性骨髓瘤的反应适应性挽</span><span style="color: black;">救</span><span style="color: black;">——澳大利亚白血病和淋巴瘤组</span><span style="color: black;"> (ALLG) </span><span style="color: black;">MM</span><span style="color: black;">17<span style="color: black;">实验</span></span></p><span style="color: black;">R.Turner</span><span style="color: black;"><span style="color: black;">1</span></span><span style="color: black;">| H.Quach</span><span style="color: black;"><span style="color: black;">2,3</span></span><span style="color: black;">| N.Horvath</span><span style="color: black;"><span style="color: black;">4</span></span><span style="color: black;">| I.Kerridge</span><span style="color: black;"><span style="color: black;">5</span></span><span style="color: black;">| E.Lee</span><span style="color: black;"><span style="color: black;">6</span></span><span style="color: black;">| E.Morris</span><span style="color: black;"><span style="color: black;">7</span></span><span style="color: black;">| A.Kalff</span><span style="color: black;"><span style="color: black;">1</span></span><span style="color: black;">| T.Khong</span><span style="color: black;"><span style="color: black;">1</span></span><span style="color: black;">| J.Reynolds</span><span style="color: black;"><span style="color: black;">1,8</span></span><span style="color: black;">| A.Spencer</span><span style="color: black;"><span style="color: black;">1,8</span></span><span style="color: black;"><span style="color: black;">1</span></span><span style="color: black;">Alfred Health, Melbourne, Victoria, Australia;</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;">St Vincents Hospital, Melbourne, Victoria, Australia; et,al.</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">DOI: 10</span><span style="color: black;">.1111/bjh.18914</span></p><img src="https://mmbiz.qpic.cn/mmbiz_png/jiamWpYQI4KXuhpBwicUxodIzgsSas1LE6CTPQ1YTBXptWyzchx0DfeMlO5Q7Oy84vXKia6drsya9vcs0IKlAiciaAA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">摘要</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">咱们</span><span style="color: black;">评定</span>了结合卡非佐米-沙利度胺-地塞米松 (KTd) 和自体干细胞移植 (ASCT) 的</span><strong style="color: blue;"><span style="color: black;">再诱导</span></strong><span style="color: black;">治疗新诊断的多发性骨髓瘤 (NDMM) 难治性或对非 IMID 硼替佐米诱导反应欠佳的<span style="color: black;">状况</span>。</span><strong style="color: blue;"><span style="color: black;"> KTd <span style="color: black;">解救</span><span style="color: black;">办法</span><span style="color: black;">包含</span><span style="color: black;">每日</span> 100 mg 沙利度胺</span></strong><span style="color: black;">和 20 mg 口服地塞米松，联合 56 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;">卡非佐米，<span style="color: black;">每一个</span> 28 天周期的第 1、2、8、9、15 和 16 天。四个周期后，达到严格完全缓解的<span style="color: black;">病人</span>继续进行 ASCT，而<span style="color: black;">哪些</span><span style="color: black;">无</span>达到完全缓解的<span style="color: black;">病人</span>，继续接受两个周期<span style="color: black;">而后</span>进行ASCT。巩固治疗<span style="color: black;">包含</span>两个周期的 KTd，<span style="color: black;">而后</span>是 Td，直至 ASCT 治疗后总共 12 个月。<span style="color: black;">重点</span>终点是 ASCT 前 KTd 的总体缓解率 (ORR)。共招募了 50 名<span style="color: black;">病人</span>，</span><strong style="color: blue;"><span style="color: black;">ORR 为 78%</span></strong><span style="color: black;">，ASCT 后 12 个月时意向治疗人群中EuroFlow MRD 阴性率为34%，可<span style="color: black;">评定</span>人群为65%。随访 > 38 个月后，中位 PFS 和 OS 尚未达到，</span><strong style="color: blue;"><span style="color: black;">36 个月时的 PFS 和 OS 分别为 64% 和 80%</span></strong><span style="color: black;">。KTd 的耐受性良好，3 级和 4 级以上不良事件<span style="color: black;">出现</span>率分别为 32% 和 10%。KTd 与 ASCT 的反应适应性利用与功能性高危 NDMM 的高质量反应和持久<span style="color: black;">疾患</span><span style="color: black;">掌控</span><span style="color: black;">关联</span>。</span></p><img src="https://mmbiz.qpic.cn/mmbiz_png/jiamWpYQI4KXuhpBwicUxodIzgsSas1LE6CTPQ1YTBXptWyzchx0DfeMlO5Q7Oy84vXKia6drsya9vcs0IKlAiciaAA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">重要</span>词</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">功能性高危、</span><span style="color: black;">KTd、微小残留病、多发性骨髓瘤、反应适应性治疗 </span></p><img src="https://mmbiz.qpic.cn/mmbiz_png/jiamWpYQI4KXuhpBwicUxodIzgsSas1LE6CTPQ1YTBXptWyzchx0DfeMlO5Q7Oy84vXKia6drsya9vcs0IKlAiciaAA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">引言</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">近几十年来，随着高剂量化疗<span style="color: black;">前提</span>下的自体干细胞移植（</span><span style="color: black;">ASCT）的<span style="color: black;">显现</span>以及诱导治疗新型<span style="color: black;">药品</span>的<span style="color: black;">显现</span>，多发性骨髓瘤（MM）的<span style="color: black;">存活</span>率显着<span style="color: black;">加强</span>。</span><span style="color: black;">在符合移植资格</span><span style="color: black;">(TE) 的新诊断多发性骨髓瘤 (NDMM) 中，诱导治疗和 ASCT 的反应深度已被证明是<span style="color: black;">病人</span>预后的有力预测<span style="color: black;">原因</span>，可实现非常好的部分缓解 (VGPR) 或更高 ，以及<span style="color: black;">近期</span>实现的微小残留病 (MRD) 阴性，与<span style="color: black;">存活</span>率的<span style="color: black;">加强</span><span style="color: black;">关联</span>。</span><span style="color: black;"><span style="color: black;">尤其</span>是蛋白酶体<span style="color: black;">控制</span>剂</span><span style="color: black;"> (PI) 和免疫调节剂 (IMiD) 的组合，经证实<span style="color: black;">拥有</span>协同<span style="color: black;">功效</span>，与 NDMM <span style="color: black;">病人</span>前所未有的深度反应和延长<span style="color: black;">存活</span>期<span style="color: black;">相关</span>。</span><span style="color: black;">越来越多地<span style="color: black;">运用</span>序贯治疗<span style="color: black;">方法</span>，将诱导、强化</span><span style="color: black;">(ASCT)、巩固和维持治疗与 PI-IMiD 组合相结合，使临床<span style="color: black;">大夫</span>能够进一步最大限度地<span style="color: black;">加强</span> TE NDMM 人群的反应深度和治疗结果。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">硼替佐米是<span style="color: black;">第1</span>代蛋白酶体<span style="color: black;">控制</span>剂，广泛用于</span><span style="color: black;"> NDMM 的诱导<span style="color: black;">方法</span>，<span style="color: black;">表示</span>出优于传统化疗<span style="color: black;">办法</span>的疗效。<span style="color: black;">按照</span>澳大利亚和新西兰 (ANZ) 骨髓瘤及<span style="color: black;">关联</span><span style="color: black;">疾患</span>登记处 (MRDR) 的数据，85 % ANZ TE NDMM<span style="color: black;">病人</span>接受含硼替佐米诱导</span><span style="color: black;">疗法，<span style="color: black;">重点</span>是硼替佐米</span><span style="color: black;">-环磷酰胺-</span><span style="color: black;">地塞米松（</span><span style="color: black;">VCD）<span style="color: black;">三联疗法</span>。在<span style="color: black;">第1</span>个至两个治疗周期内，硼替佐米诱导的首次反应和最佳反应的中位时间<span style="color: black;">火速</span>，</span><span style="color: black;"><span style="color: black;">得到</span>快速反应可预测更长的<span style="color: black;">没</span><span style="color: black;">发展</span><span style="color: black;">存活</span>期</span><span style="color: black;">(PFS)。在这种<span style="color: black;">状况</span>下，接受两个周期的基于硼替佐米的诱导治疗后未能实现部分缓解（PR）的<span style="color: black;">病人</span>不仅不太可能实现完全缓解（CR），<span style="color: black;">况且</span>在继续硼替佐米治疗后<span style="color: black;">亦</span>可能会<span style="color: black;">显现</span> PFS 缩短的<span style="color: black;">状况</span></span><span style="color: black;">。</span><span style="color: black;">基于硼替佐米的诱导治疗</span><span style="color: black;"><span style="color: black;">无</span></span><span style="color: black;">反应，表现为</span><strong style="color: blue;"><span style="color: black;">次优反应 (SOR) </span></strong><span style="color: black;">或</span><strong style="color: blue;"><span style="color: black;">原发难治性 (1REF)</span></strong><span style="color: black;">，这种<span style="color: black;">状况</span>见于15%的移植合格<span style="color: black;">病人</span>。</span><span style="color: black;">表现出这种功能性高<span style="color: black;">危害</span>表型的<span style="color: black;">病人</span>子集的结果仍然很差，</span><span style="color: black;">PFS 和总<span style="color: black;">存活</span>期 (OS) 短得令人<span style="color: black;">没</span>法接受，<span style="color: black;">因此呢</span><span style="color: black;">表率</span>了一个<span style="color: black;">连续</span>未得到满足的临床需求的<span style="color: black;">行业</span>。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">卡非佐米</span><span style="color: black;">(K) 是一种<span style="color: black;">选取</span>性、不可逆</span><span style="color: black;">的</span><span style="color: black;">第二代PI，在结构和机制上与硼替佐米不同。它已被证明比硼替佐米能<span style="color: black;">导致</span>更深入、更持久的蛋白酶体<span style="color: black;">控制</span>，并且在用于 NDMM 和复发和/或难治性 (RR) MM 时<span style="color: black;">做为</span>单药和联合治疗均<span style="color: black;">拥有</span><span style="color: black;">显著</span>的临床疗效。临床前和临床<span style="color: black;">科研</span>还证明了 K 克服硼替佐米耐药性的能力。与 IMiD 结合<span style="color: black;">运用</span>，K 已被证明在 MM 诱导中非常有效，MRD 阴性率高且剂量限制性毒性很少。虽然这些<span style="color: black;">科研</span>中的大<span style="color: black;">都数</span>都集中在与来那度胺的组合上，但</span><strong style="color: blue;"><span style="color: black;">沙利度胺</span></strong><span style="color: black;">仍然是一种</span><strong style="color: blue;"><span style="color: black;">有效且易于<span style="color: black;">运用</span></span></strong><span style="color: black;">的 IMiD </span><span style="color: black;"><span style="color: black;">选取</span></span><span style="color: black;">，既</span><strong style="color: blue;"><span style="color: black;">不会产生<span style="color: black;">关联</span>的骨髓<span style="color: black;">控制</span></span></strong><span style="color: black;">，<span style="color: black;">亦</span></span><strong style="color: blue;"><span style="color: black;">不会对随后的外周血干细胞 (PBSC) 动员产生有害影响。</span></strong></p><img src="https://mmbiz.qpic.cn/mmbiz_png/jiamWpYQI4KXuhpBwicUxodIzgsSas1LE6CTPQ1YTBXptWyzchx0DfeMlO5Q7Oy84vXKia6drsya9vcs0IKlAiciaAA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">病人</span>和<span style="color: black;">办法</span></p><span style="color: black;">基于</span><strong style="color: blue;"><span style="color: black;">硼替佐米诱导治疗失败</span></strong><span style="color: black;">的</span><strong style="color: blue;"><span style="color: black;">TE NDMM<span style="color: black;"><span style="color: black;">病人</span></span></span></strong><span style="color: black;"><span style="color: black;">，表现为</span></span><strong style="color: blue;"><span style="color: black;">SOR</span></strong><span style="color: black;"><span style="color: black;">（其中</span> SOR </span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">定义为</span></span></strong><span style="color: black;"><span style="color: black;">两个周期后<span style="color: black;">小于</span>最小缓解</span> (MR)<span style="color: black;">）或四个周期诱导治疗后<span style="color: black;">显现</span> </span>PR</span><span style="color: black;"><span style="color: black;">，或</span></span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">难治性</span> (1REF) <span style="color: black;">诱导</span></span></strong><span style="color: black;"><span style="color: black;">，其中</span> 1REF <span style="color: black;">被</span></span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">定义为</span></span></strong><span style="color: black;"><span style="color: black;">完成诱导治疗后</span> 60 <span style="color: black;">天或</span></span><span style="color: black;"><span style="color: black;">6</span></span><span style="color: black;">0</span><span style="color: black;">天</span><span style="color: black;"><span style="color: black;">之内的<span style="color: black;">疾患</span><span style="color: black;">发展</span></span> (PD)。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">KTd <span style="color: black;">的 </span>K </span><span style="color: black;">在</span><span style="color: black;"><span style="color: black;">每</span> 28 <span style="color: black;">天周期的第 </span>1<span style="color: black;">、</span>2<span style="color: black;">、</span>8 </span><span style="color: black;">、</span><span style="color: black;">9<span style="color: black;">、</span>15 <span style="color: black;">和 </span>16 </span><span style="color: black;">天<span style="color: black;">运用</span></span><span style="color: black;"><span style="color: black;">，共四个周期，第</span> 1 <span style="color: black;">天和第 </span>2 <span style="color: black;">天<span style="color: black;">起始</span>静脉注射</span>20 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;"><span style="color: black;">剂量，<span style="color: black;">而后</span>从第</span> 8 <span style="color: black;">天<span style="color: black;">起始</span>静脉注射 </span>K 56 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;"><span style="color: black;">；</span> </span><span style="color: black;"><span style="color: black;">每一个</span>四周的周期中</span><strong style="color: blue;"><span style="color: black;">T</span></strong><strong style="color: blue;"><span style="color: black;"><span style="color: black;">每日</span> 100 mg</span></strong><span style="color: black;">，</span><span style="color: black;"><span style="color: black;">d</span>在</span><span style="color: black;"><span style="color: black;">第</span> 1<span style="color: black;">、</span>2<span style="color: black;">、</span>8<span style="color: black;">、</span>9<span style="color: black;">、</span>15 <span style="color: black;">和 </span>16 <span style="color: black;">天口服 </span>20 mg<span style="color: black;">。</span>K<span style="color: black;">剂量基于 </span>Ib/II <span style="color: black;">期数据</span></span><span style="color: black;">中</span><span style="color: black;">证明</span><span style="color: black;">的</span><span style="color: black;"> RRMM <span style="color: black;"><span style="color: black;">病人</span>每周两次静脉注射 </span>56 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;"><span style="color: black;">的耐受性和有效性。</span>VTE <span style="color: black;">和抗病毒预防<span style="color: black;">根据</span><span style="color: black;">公司</span>惯例进行。</span></span></p><span style="color: black;"><span style="color: black;">经过四个周期的</span> KTd <span style="color: black;">后，<span style="color: black;">病人</span>达到严格的 </span>CR<span style="color: black;">，</span></span><span style="color: black;">出于本<span style="color: black;">科研</span>的目的，将其定义为形态正常的骨髓、免疫固定阴性以及所<span style="color: black;">触及</span>的游离轻链</span><span style="color: black;"> (FLC) <span style="color: black;"><span style="color: black;">成份</span>和 </span>kappa/lambda <span style="color: black;">比率均正常化，但<span style="color: black;">无</span>浆细胞克隆性定量，<span style="color: black;">而后</span>进行 </span>G-CSF <span style="color: black;">动员的 </span>PBSC <span style="color: black;">收集。</span></span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><CR</span></strong><span style="color: black;"> <span style="color: black;">的<span style="color: black;">病人</span>接受</span></span><strong style="color: blue;"><span style="color: black;"><span style="color: black;"><span style="color: black;">另一</span>两个周期的</span> KTd</span></strong><span style="color: black;"><span style="color: black;">，<span style="color: black;">而后</span>用</span> G-CSF <span style="color: black;">刺激 </span>PBSC <span style="color: black;">收集。所有</span>CD34 <span style="color: black;">细胞</span>≥200 <span style="color: black;">万</span>/<span style="color: black;">公斤</span> <span style="color: black;">的<span style="color: black;">病人</span>均接受了马法兰 </span>200 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;"> <span style="color: black;"><span style="color: black;">前提</span></span> ASCT<span style="color: black;">。</span></span><strong style="color: blue;"><span style="color: black;">巩固治疗</span></strong><span style="color: black;">从</span><span style="color: black;"> ASCT <span style="color: black;">后第 </span>100 <span style="color: black;">天<span style="color: black;">起始</span>，<span style="color: black;">包含</span></span></span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">两个周期的</span> KTd</span></strong><span style="color: black;"><span style="color: black;">，<span style="color: black;">而后</span>是</span> </span><strong style="color: blue;"><span style="color: black;">Td</span></strong><span style="color: black;"><span style="color: black;">，直到</span> PD<span style="color: black;">、不可接受的毒性或</span>ASCT <span style="color: black;">后总</span></span><span style="color: black;"><span style="color: black;">共</span> 12 <span style="color: black;">个月的治疗（</span></span><strong style="color: blue;"><span style="color: black;">10 <span style="color: black;">个周期的 </span>Td</span></strong><span style="color: black;">）。</span></p><img src="https://mmbiz.qpic.cn/mmbiz_png/jiamWpYQI4KXuhpBwicUxodIzgsSas1LE6CTPQ1YTBXptWyzchx0DfeMlO5Q7Oy84vXKia6drsya9vcs0IKlAiciaAA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">结果</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">2016 年 9 月和 2018 年 4 月</span><span style="color: black;"><span style="color: black;">时期</span>从澳大利亚六个地点招募了</span><span style="color: black;"> 50 名<span style="color: black;">病人</span>。<span style="color: black;">经过</span>反向 Kaplan-Meier 估计，<span style="color: black;">存活</span>期中位潜在随访时间为 40.1 个月（范围 29-49 个月），缓解状态为 38.6 个月（范围 29-49 个月）。<span style="color: black;">实验</span>注册时的平均年龄为 58 岁，男性比例 (76%) 高于女性。</span><strong style="color: blue;"><span style="color: black;"> 24% 的<span style="color: black;">病人</span>被诊断<span style="color: black;">身患</span> 3 期<span style="color: black;">疾患</span></span></strong><span style="color: black;">（<span style="color: black;">按照</span>国际分期系统 ），</span><strong style="color: blue;"><span style="color: black;">32% 的<span style="color: black;">病人</span>表现出高<span style="color: black;">危害</span> (HR) 或超高<span style="color: black;">危害</span> (UHR) 细胞遗传学<span style="color: black;">反常</span></span></strong><span style="color: black;">（表 1）</span><span style="color: black;">。</span><span style="color: black;">两名<span style="color: black;">病人</span>的<span style="color: black;">疾患</span><span style="color: black;">周期</span>未知，九名<span style="color: black;">病人</span>的细胞遗传学结果<span style="color: black;">没</span>法获</span><span style="color: black;">得。</span><span style="color: black;"> 所有<span style="color: black;">病人</span>均已<span style="color: black;">起始</span> CyBorD 一线治疗，<span style="color: black;">因此呢</span>在</span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">科研</span><span style="color: black;">起始</span>时未接受过 IMID 治疗</span></strong><span style="color: black;">。在<span style="color: black;">科研</span><span style="color: black;">起始</span>时，30% 的<span style="color: black;">病人</span></span><span style="color: black;">为难治性（</span><span style="color: black;">1REF</span><span style="color: black;">）</span><span style="color: black;">，70% 的<span style="color: black;">病人</span>表现出 SOR（18 例 <span style="color: black;">病人</span>在两个周期后未能达到 MR，17 例 <span style="color: black;">病人</span>在四个周期后未能达到 PR）。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">表</span><span style="color: black;"> 1 基线人口统计和<span style="color: black;">疾患</span>特征</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/RgoDMXJyUwb0UFWDVfSpSoGO0pLjAD5QLXlKbR8vz0Olq9XRbl1Hw1OT0GtWrmCzGVFjE53wpFwALiarVkBsYAA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">缩写：</span><span style="color: black;">HR，高<span style="color: black;">危害</span>，定义为存在 del 17p、t(4;14)、t(14;16)、t(4;20)、增益 1q 、非超二倍体核型、核型分析中 13 号染色体缺失；ISS，国际分期系统；MR，最小反应；NA，不可用；PR，部分反应；SR、标准<span style="color: black;">危害</span>、所有其他细胞遗传学<span style="color: black;">反常</span> (CA)；UHR，超高<span style="color: black;">危害</span>，定义为≥3 CA。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">44 名<span style="color: black;">病人</span> (88%) 完<span style="color: black;">成为了</span> 4 个或<span style="color: black;">更加多</span>周期的 KTd 挽救治疗</span></strong><span style="color: black;">，其中 5 名<span style="color: black;">病人</span><span style="color: black;">得到</span>了免疫固定阴性 CR，并在 4 个周期后直接进行 ASCT。在所有仍在<span style="color: black;">实验</span>中并接受动员的<span style="color: black;">病人</span>中，PBSC 动员均成功（收集≥200 万/</span><span style="color: black;"><span style="color: black;">公斤</span></span><span style="color: black;"> CD34）。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;"><span style="color: black;">在最初的四个周期后<span style="color: black;">评定</span>，</span></span></strong><span style="color: black;"><span style="color: black;">观察到的</span></span><strong style="color: blue;"><span style="color: black;"> KTd <span style="color: black;">挽救的 </span>ORR <span style="color: black;">为 </span>78%</span></strong><span style="color: black;"><span style="color: black;">（</span>95% <span style="color: black;">可信区间：</span>64.4–87.1%<span style="color: black;">），</span></span><span style="color: black;">满足双重概念验证标准（观察到的</span><span style="color: black;"> ORR ≥50%<span style="color: black;">，真实 </span>ORR <span style="color: black;">超过 </span>30% <span style="color: black;">的后验概率</span>≥0.90<span style="color: black;">）。虽然额外两个周期 </span>KTd <span style="color: black;">的益处不大，<span style="color: black;">仅有</span><span style="color: black;">另一</span>两名<span style="color: black;">病人</span>达到免疫固定阴性 </span>CR<span style="color: black;">，但在连续治疗<span style="color: black;">周期</span>后，缓解率有所加深，</span></span><span style="color: black;"><span style="color: black;">病人</span>的</span><strong style="color: blue;"><span style="color: black;">CR </span></strong><span style="color: black;"><span style="color: black;">从</span> 4 <span style="color: black;">个挽救 </span>KTd <span style="color: black;">周期后的 </span></span><strong style="color: blue;"><span style="color: black;">16%</span></strong><span style="color: black;"> <span style="color: black;"><span style="color: black;">增多</span>到</span> Td <span style="color: black;">巩固完成时的</span></span><strong style="color: blue;"><span style="color: black;">54%</span></strong><span style="color: black;">（图</span><span style="color: black;">1<span style="color: black;">）。</span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_png/RgoDMXJyUwb0UFWDVfSpSoGO0pLjAD5QCWPmQSnibx0y4v86L6EOhibACKNCyZe0oxffV5riccGgMpcoxLu0aZScA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">图</span><span style="color: black;"> 1. KTd 挽救、ASCT、KTd 巩固和 Td 巩固后意向治疗<span style="color: black;">病人</span>群体的<span style="color: black;">疾患</span>反应。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">留意</span>向治疗</span><span style="color: black;"> (ITT) <span style="color: black;">人群中，</span>24%<span style="color: black;">、</span>36%<span style="color: black;">、</span>40% <span style="color: black;">和 </span>34% <span style="color: black;">的<span style="color: black;">病人</span>实现了 </span>EuroFlow MRD <span style="color: black;">阴性 </span>(<10</span><span style="color: black;"><span style="color: black;">−</span><span style="color: black;">5</span></span><span style="color: black;">)<span style="color: black;">，</span></span><span style="color: black;">在</span><strong style="color: blue;"><span style="color: black;">挽救后</span></strong><span style="color: black;">（最初四个周期）、</span><strong style="color: blue;"><span style="color: black;">ASCT <span style="color: black;">后</span></span></strong><span style="color: black;">、</span><strong style="color: blue;"><span style="color: black;">巩固后</span></strong><span style="color: black;"><span style="color: black;">和</span> </span><strong style="color: blue;"><span style="color: black;">Td <span style="color: black;">后</span></span></strong><span style="color: black;">时间点时分别占</span><span style="color: black;"><span style="color: black;">可<span style="color: black;">评定</span>人群的</span> 31%<span style="color: black;">、</span>56%<span style="color: black;">、</span>59% <span style="color: black;">和 </span>65%<span style="color: black;">（图 </span>2<span style="color: black;">）。预期的 </span>200 <span style="color: black;">个 </span>MRD <span style="color: black;">样本中有 </span>69 <span style="color: black;">个<span style="color: black;">没</span>法用于<span style="color: black;">评定</span>（<span style="color: black;">因为</span><span style="color: black;">疾患</span><span style="color: black;">发展</span>、退出<span style="color: black;">实验</span>或样本丢失），并被<span style="color: black;">做为</span></span>MRD <span style="color: black;">阳性纳入治疗人群意向中。</span>14 <span style="color: black;">个 </span>MRD <span style="color: black;">阴性但细胞计数<span style="color: black;">不睬</span>想的血液稀释样品<span style="color: black;">留意</span>向治疗人群和可<span style="color: black;">评定</span>人群中均被列为 </span>MRD <span style="color: black;">阳性。</span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_png/RgoDMXJyUwb0UFWDVfSpSoGO0pLjAD5QPqribw7zAkRU2bwHLVZp7JibEibWdPsJSt49dsEv5jV1fY6hFguO8LY6Q/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">图 2. </span><span style="color: black;">意向治疗<span style="color: black;">病人</span>群体和可<span style="color: black;">评定</span><span style="color: black;">病人</span>群体KTd 挽救、ASCT、KTd 巩固和 Td 巩固后的 EuroFlow MRD 阴性率（<1in 10</span><span style="color: black;"><span style="color: black;">5</span></span><span style="color: black;">）。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">12<span style="color: black;">、</span>24 <span style="color: black;">和</span>36 <span style="color: black;">个月时的 </span>PFS <span style="color: black;">分别为 </span>80%</span></strong><span style="color: black;"> (95% CI: 66–88.7)<span style="color: black;">、</span></span><strong style="color: blue;"><span style="color: black;">68% </span></strong><span style="color: black;">(95% CI: 53.1–79) <span style="color: black;">和</span></span><strong style="color: blue;"><span style="color: black;">64%</span></strong><span style="color: black;">(95% CI: 49–75.5)<span style="color: black;">，</span></span><strong style="color: blue;"><span style="color: black;">OS <span style="color: black;">为</span></span></strong><strong style="color: blue;"><span style="color: black;">分别为</span></strong><strong style="color: blue;"><span style="color: black;"> 88%</span></strong><span style="color: black;"><span style="color: black;">（</span>95% CI<span style="color: black;">：</span>75.2-94.4<span style="color: black;">）、</span></span><strong style="color: blue;"><span style="color: black;">82%</span></strong><span style="color: black;"><span style="color: black;">（</span>95% CI<span style="color: black;">：</span>68.2-90.2<span style="color: black;">）和 </span></span><strong style="color: blue;"><span style="color: black;">80%</span></strong><span style="color: black;"><span style="color: black;">（</span>95% CI<span style="color: black;">：</span>65.8-88.6<span style="color: black;">）（图 </span>3A<span style="color: black;">、</span>B<span style="color: black;">）。</span></span><span style="color: black;">随访结束时，中位</span><span style="color: black;"> PFS <span style="color: black;">和 </span>OS <span style="color: black;">尚未</span></span><span style="color: black;">达到。达到<span style="color: black;">发展</span>或死亡时间的下四分位为</span><span style="color: black;"> 14.49 <span style="color: black;">个月（</span>95% CI<span style="color: black;">：</span>3.54-41.53 <span style="color: black;">个月），</span>OS<span style="color: black;">（</span>95% CI<span style="color: black;">：</span>19.1-NR <span style="color: black;">个月）。</span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_png/RgoDMXJyUwb0UFWDVfSpSoGO0pLjAD5QT9oibqibVFPrLibAvJu8MFF1aKseiaiaYJEKMorX8syZru6fhiaWk4jnPsXA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">图</span><span style="color: black;">3. 中位随访时间分别为 40.1 个月（范围 29-49 个月）和 38.6 个月（范围 29-49 个月）后的<span style="color: black;">没</span><span style="color: black;">发展</span>生存期 (A) 和总<span style="color: black;">存活</span>期 (B)。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">较高的</span> ISS <span style="color: black;">分期和不良<span style="color: black;">危害</span>细胞遗传学<span style="color: black;">反常</span>与缩短的 </span>PFS <span style="color: black;">和 </span>OS <span style="color: black;"><span style="color: black;">关联</span>（图 </span>4<span style="color: black;">）</span></span><span style="color: black;">，而</span><span style="color: black;"> SOR <span style="color: black;">和 </span>1 REF <span style="color: black;"><span style="color: black;">病人</span>队列之间的 </span>ORR<span style="color: black;">（</span>80% <span style="color: black;">与</span>73%<span style="color: black;">，</span>p=NS<span style="color: black;">）、</span>PFS <span style="color: black;">或 </span>OS <span style="color: black;"><span style="color: black;">无</span>显</span></span><span style="color: black;">著</span><span style="color: black;"><span style="color: black;">差异，请<span style="color: black;">重视</span>，这项<span style="color: black;">科研</span>并<span style="color: black;">不可</span>确定这两个队列之间的差异，但</span></span><span style="color: black;"><span style="color: black;">咱们</span>之前<span style="color: black;">已然</span>在现实世界中展示了</span><span style="color: black;"> REF <span style="color: black;">的结果优于</span>SOR。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><img src="https://mmbiz.qpic.cn/mmbiz_png/RgoDMXJyUwb0UFWDVfSpSoGO0pLjAD5QIm3M3RHy6OGJxks3AhvpNvvGHmic2ick7yve7zJSUO6jawQICZHLbMUQ/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">图</span><span style="color: black;">4. ISS（A、B）和细胞遗传学亚组（C、D）的<span style="color: black;">没</span><span style="color: black;">发展</span><span style="color: black;">存活</span>期和总<span style="color: black;">存活</span>期。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">ASCT <span style="color: black;">前和 </span>KTd <span style="color: black;">巩固后的 </span>MRD <span style="color: black;">阴性与 </span>PFS <span style="color: black;">改善<span style="color: black;">关联</span>（图 </span>5<span style="color: black;">）。<span style="color: black;">实验</span>随访<span style="color: black;">时期</span>共报告</span>10<span style="color: black;">例死亡，其中</span>8<span style="color: black;">例因<span style="color: black;">疾患</span><span style="color: black;">发展</span>死亡。其中五名<span style="color: black;">病人</span>在复发时表现出高度侵袭性的髓外<span style="color: black;">药品</span>难治性<span style="color: black;">疾患</span>而死亡。</span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><strong style="color: blue;"><span style="color: black;">KTd <span style="color: black;">方法</span><span style="color: black;">拥有</span>良好的耐受性和可接受的毒性特征</span></strong><span style="color: black;">。停止治疗的<span style="color: black;">重点</span><span style="color: black;">原由</span>是 PD，<span style="color: black;">出现</span>在 18 名<span style="color: black;">病人</span>（36%）中。AE <span style="color: black;">引起</span>四例<span style="color: black;">病人</span>退出<span style="color: black;">科研</span>，两例死亡与<span style="color: black;">疾患</span><span style="color: black;">发展</span><span style="color: black;">没</span>关，分别归因于败血症和继发性恶性肿瘤。3 级和 4 级以上 AE <span style="color: black;">出现</span>率分别为 32%</span><span style="color: black;">和</span><span style="color: black;">10%。>10% 的<span style="color: black;">病人</span><span style="color: black;">出现</span>任何级别的 AE，<span style="color: black;">包含</span>上<span style="color: black;">呼气</span>道感染 (56%)、<span style="color: black;">周边</span>神经病变 (PN，42%)、肌肉骨骼<span style="color: black;">病痛</span> (32%)、<span style="color: black;">呼气</span>困难 (28%)、疲劳或嗜睡 (28%) 和 便秘</span><span style="color: black;">（</span><span style="color: black;">28%）。正如预期的那样，血液学毒性非常容易<span style="color: black;">掌控</span>，3/4 级血小板减少症或中性粒细胞减少症仅分别<span style="color: black;">出现</span>在 4% 和 6% 的<span style="color: black;">病人</span>中。</span><span style="color: black;"><span style="color: black;">要紧</span>的是，<span style="color: black;">无</span><span style="color: black;">显现</span>与血液学<span style="color: black;">关联</span>的钾剂量减少或治疗延迟的<span style="color: black;">状况</span>。在这种较高剂量的钾水平下，<span style="color: black;">无</span>观察到<span style="color: black;">显著</span>的心脏毒性（≥</span><span style="color: black;">4级），14%的<span style="color: black;">病人</span>报告了3级心脏<span style="color: black;">关联</span>事件（ 高血压 n=3，未分化<span style="color: black;">呼气</span>困难 n=2，心力衰竭 n=1，心房颤动 n=1）。</span></p><img src="https://mmbiz.qpic.cn/mmbiz_png/jiamWpYQI4KXuhpBwicUxodIzgsSas1LE6CTPQ1YTBXptWyzchx0DfeMlO5Q7Oy84vXKia6drsya9vcs0IKlAiciaAA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">讨论</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">KTd <span style="color: black;">做为</span>诱导疗法之前已在欧洲骨髓瘤网络 Carthedex <span style="color: black;">实验</span>的一线环境中进行了<span style="color: black;">评定</span>，该<span style="color: black;">实验</span>采用 KTd 诱导、ASCT 和巩固的序贯治疗，每周两次 K ，四个剂量水平（27、36、45 和 56 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;">） 该人群中 KTd 诱导的 ORR 为 93%，CR 和 VGPR 分别为 18% 和 65%，中位 PFS 为 58 个月（95% CI：45-67 个月），OS 为 83 个月（95% CI：83 个月 NR）。然而，从 56 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;"> 剂量水平得出的结论受到该队列中样本量较小 (n=20) 的限制。</span><strong style="color: blue;"><span style="color: black;">MM17 <span style="color: black;">实验</span></span></strong><span style="color: black;">是迄今为止</span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">第1</span>个对基于硼替佐米一线诱导<span style="color: black;">没</span>反应的<span style="color: black;">病人</span><span style="color: black;">运用</span>类似<span style="color: black;">方法</span>的<span style="color: black;">实验</span></span></strong><span style="color: black;">，并仅加入较高的 56 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;"> 每周两次 K 剂量。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">近期</span>，在 IFM <span style="color: black;">实验</span>中<span style="color: black;">科研</span>了 K 与来那度胺和地塞米松 (KRd) 联合<span style="color: black;">做为</span> TE NDMM 的前期治疗。<span style="color: black;">根据</span>类似的序贯 KRd 诱导<span style="color: black;">实验</span>设计（四个周期，卡非佐米 36 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;">，每周两次）， 美法仑 ASCT、KRd 巩固治疗（四个周期）和来那度胺维持治疗（1 年），CR 或更高的比率分别为 23%、42%、64% 和 76%。KRd 诱导结束时 ORR 为 98%。<span style="color: black;">按照</span>可<span style="color: black;">评定</span>的<span style="color: black;">病人</span>群体，在巩固治疗完成时，<span style="color: black;">运用</span>灵敏度为 2.5 × 10</span><span style="color: black;"><span style="color: black;">−</span><span style="color: black;">5</span></span><span style="color: black;">的7色面板，MFC的MRD阴性率为 93%，<span style="color: black;">运用</span>下一代测序 (10</span><span style="color: black;"><span style="color: black;">−</span><span style="color: black;">6</span></span><span style="color: black;">) 时，MRD阴性率为 63%，比例与<span style="color: black;">咱们</span>在Td巩固结束时可<span style="color: black;">评定</span><span style="color: black;">病人</span>群体中 EuroFlow MRD 阴性率为 64% 的证明一致。然而<span style="color: black;">必须</span><span style="color: black;">重视</span>的是，与本<span style="color: black;">科研</span>相比，一线 IFM <span style="color: black;">科研</span>中高<span style="color: black;">危害</span><span style="color: black;">病人</span>的比例要低得多（ISS III 6%，不良 CG 21%，分别对比 ISS III 24% 和不良 CG 38%），正如在未接受过治疗的人群中预期的那样。遵循类似的诱导、强化和巩固治疗模式，在FORTE 随机 2 期<span style="color: black;">实验</span>的TE NDMM中，KRd <span style="color: black;">亦</span>与卡非佐米-环磷酰胺-地塞米松 (KCd)进行了直接比较。<span style="color: black;">一样</span><span style="color: black;">运用</span>每周两次 36 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;">的 K 剂量，在这个较<span style="color: black;">青年</span>的人群（年龄截止65 岁或以下）中，在 KRd 和 KCd 诱导后，VGPR 或更高水平<span style="color: black;">出现</span>率分别为 70% 和 53%。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">尽管采用的剂量水平比大<span style="color: black;">都数</span>其他基于</span><span style="color: black;"> K 的三联</span><span style="color: black;">组合</span><span style="color: black;">更高，但 MM17 KTd <span style="color: black;">方法</span>被<span style="color: black;">发掘</span>是安全且耐受性良好的。3 级 (32%) 和 ≥ 4 级 (10%) AE 的<span style="color: black;">出现</span>率与 Carthadex <span style="color: black;">实验</span>（<span style="color: black;">触及</span> K 的四个剂量水平）以及其他 K 三联</span><span style="color: black;">组合</span><span style="color: black;"><span style="color: black;">科研</span>报告的结果<span style="color: black;">类似</span>。</span><span style="color: black;">虽然K与硼替佐米相比，</span><span style="color: black;"><span style="color: black;">周边</span>神经病变 (PN) <span style="color: black;">出现</span>率</span><span style="color: black;">较低，但</span><span style="color: black;">沙利度胺治疗</span><span style="color: black;">，尤其</span><span style="color: black;">是以 ASCT 后维持的形式，</span><span style="color: black;">始终</span><span style="color: black;">与较高的 PN <span style="color: black;">出现</span>率<span style="color: black;">关联</span>。</span><span style="color: black;">本<span style="color: black;">科研</span>的结果令人<span style="color: black;">安心</span>地<span style="color: black;">显示</span>，</span><span style="color: black;">ASCT 前后<span style="color: black;">运用</span></span><strong style="color: blue;"><span style="color: black;"> KTd 并未<span style="color: black;">引起</span> PN <span style="color: black;">出现</span>率显</span></strong><strong style="color: blue;"><span style="color: black;">著</span></strong><strong style="color: blue;"><span style="color: black;"><span style="color: black;">上升</span></span></strong><span style="color: black;">（任何等级=42%；3 级=6%，≥4</span><span style="color: black;">级<span style="color: black;">没</span></span><span style="color: black;">）。与其他 K-Thal 组合相比，PN <span style="color: black;">出现</span>率确实<span style="color: black;">小于</span>基于硼替佐米的治疗<span style="color: black;">方法</span>。心脏毒性，一种<span style="color: black;">报告</span>充分的K 治疗<span style="color: black;">关联</span> AE仅限于 3 级 (14%) 或更低的事件，频率与其他基于 K 的治疗<span style="color: black;">方法</span><span style="color: black;">类似</span>。</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">ALLG MM17 <span style="color: black;">实验</span>的<span style="color: black;">最后</span>分析<span style="color: black;">显示</span>，在</span><strong style="color: blue;"><span style="color: black;">基于硼替佐米治疗<span style="color: black;">方法</span>失败的 NDMM <span style="color: black;">病人</span></span></strong><span style="color: black;">中， </span><strong style="color: blue;"><span style="color: black;">KTd</span></strong><strong style="color: blue;"><span style="color: black;">挽</span></strong><strong style="color: blue;"><span style="color: black;">救的<span style="color: black;">初期</span>反应适应性</span></strong><span style="color: black;">可带来</span><strong style="color: blue;"><span style="color: black;">高反应率和高水平的 MRD 阴性</span></strong><span style="color: black;">结果。序贯 MRD <span style="color: black;">评定</span>进一步证明序贯巩固和维持治疗能够最大限度地<span style="color: black;">加强</span>反应深度，从而实现持久的 PFS 和 OS。安全数据<span style="color: black;">显示</span>，剂量为 56 mg/m</span><span style="color: black;"><span style="color: black;">2</span></span><span style="color: black;"> 的 K 与沙利度胺和地塞米松联合<span style="color: black;">运用</span>，<span style="color: black;">做为</span>诱导和巩固治疗<span style="color: black;">拥有</span>良好的耐受性，<span style="color: black;">拥有</span>可接受的毒性特征，<span style="color: black;">要紧</span>的是，对PBSC动员<span style="color: black;">无</span><span style="color: black;">显著</span>的<span style="color: black;">消极</span>影响。</span></p><span style="color: black;">翻译：<span style="color: black;"><span style="color: black;"><span style="color: black;">申峰梅</span></span></span> 审核：申峰梅 编辑：俞红倩</span>提取码<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">9b09</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_jpg/RgoDMXJyUwabxiayyaJUxibcw6zvy6mMUHPUlUjiaq9I7vE89s2aTlulAgfHSmKMPribjlNzMbuvpraaBjzbDnp2Zw/640?wx_fmt=jpeg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
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