多发性骨髓瘤：这类癌症再亦不是绝症，新疗法汇总
<img src="https://mmbiz.qpic.cn/mmbiz_png/ZbHdNdNfVmlibUREiaXA5v9BUxULKcfJchibRc0XAD68NbHHRmK5VnVEoxbibHgKxPTvKIAnt30sahJbHoEwsMQ3XA/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">癌症不分贵贱，但不同癌症的关注度却有着天壤之别。像肺癌、肝癌、乳腺癌<span style="color: black;">这般</span>的“明星”癌种，大街上随便拉个人起码都听说过这种病，但<span style="color: black;">另一</span><span style="color: black;">有些</span><span style="color: black;">病人</span>人数并不少的癌症却有些“鲜为人知”，<span style="color: black;">例如</span><span style="color: black;"><strong style="color: blue;">多发性骨髓瘤</strong></span></span><span style="color: black;">（MM）</span><span style="color: black;">。</span><span style="color: black;">MM是仅次于白血病的第二大血液肿瘤，大约能占<span style="color: black;">所有</span>癌症的1%，血液肿瘤的10%。据统计，<span style="color: black;">全世界</span>每年的MM新发病例<span style="color: black;">大概</span>17.5万例，11.7万人因MM死亡</span><span style="color: black;"><span style="color: black;"></span></span><span style="color: black;">。</span><span style="color: black;"><span style="color: black;">这般</span>一种<span style="color: black;">平常</span>但不知名的癌症有什么症状，又该怎么治疗呢？</span><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/ZbHdNdNfVmm3IwoC7Yym8RfS58mtcorSrGgEa2gMaySXXXwWSnxOuUoQMHibA9S06DQl3khO7MLWfCtezJKgU5A/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;"><strong style="color: blue;"><span style="color: black;">多发性骨髓瘤是什么？怎么治？</span></strong></span></p><span style="color: black;">MM是一种浆细胞<span style="color: black;">导致</span>的肿瘤。浆细胞<span style="color: black;">便是</span>终末分化的B细胞，<span style="color: black;">重点</span>负责分泌抗体，对抗侵入人体的<span style="color: black;">各样</span>病原体。在病情发展到MM之前，<span style="color: black;">非常多</span>MM<span style="color: black;">病人</span>最初的表现<span style="color: black;">便是</span><span style="color: black;"><strong style="color: blue;"><span style="color: black;">道理</span>不明的单克隆丙种球蛋白血症</strong></span></span><span style="color: black;">（MUGS）</span><span style="color: black;">，这<span style="color: black;">亦</span>是MM的<span style="color: black;">第1</span>个<span style="color: black;">周期</span>。</span><span style="color: black;">之后，克隆性浆细胞在骨髓中<span style="color: black;">持续</span>增殖，<span style="color: black;">逐步</span><span style="color: black;">发展</span>为MM的第二个<span style="color: black;">周期</span>——</span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">阴燃多发性骨髓瘤</span></span></strong><span style="color: black;"><span style="color: black;">（或<span style="color: black;">叫作</span>为冒烟型多发性骨髓瘤，SMM）</span></span><span style="color: black;">。<span style="color: black;">此时</span><span style="color: black;">疾患</span>还<span style="color: black;">处在</span>恶变的边缘，<span style="color: black;">病人</span><span style="color: black;">一般</span><span style="color: black;">亦</span><span style="color: black;">无</span><span style="color: black;">显著</span>的症状，但骨髓里<span style="color: black;">已然</span>有了<span style="color: black;">海量</span>的克隆性浆细胞。</span><span style="color: black;">随着克隆性浆细胞进一步完成癌变，<span style="color: black;">作为</span>恶性浆细胞，病情<span style="color: black;">亦</span><span style="color: black;">发展</span>为真正的多发性骨髓瘤。此时癌细胞在骨髓中<span style="color: black;">海量</span>增殖，侵占骨髓空间，<span style="color: black;">病人</span>会<span style="color: black;">显现</span><span style="color: black;"><strong style="color: blue;">贫血、溶血性骨病</strong></span>等症状。<span style="color: black;">因为</span>癌细胞分泌的<span style="color: black;">海量</span>抗体蛋白在肾脏中沉积，有些<span style="color: black;">病人</span>还会<span style="color: black;">出现</span><span style="color: black;"><strong style="color: blue;">急性肾<span style="color: black;">损害</span></strong></span>。</span><span style="color: black;">在MM之后，恶性浆细胞还会进一步丢失表面的CD56等粘附分子，<span style="color: black;">海量</span>进入血液，<span style="color: black;">作为</span>MM的最后一个<span style="color: black;">周期</span>——<span style="color: black;"><strong style="color: blue;">浆细胞白血病</strong></span>，很难治疗，<span style="color: black;">病人</span>预后很差。</span><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/ZbHdNdNfVmm3IwoC7Yym8RfS58mtcorSez4lO9PHep8kqUUAA3ibh0uUo06nhs4mquiamqL8ogDrlicYJxEkia4hUQ/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">多发性骨髓瘤的发展</span><span style="color: black;">大<span style="color: black;">都数</span>MM<span style="color: black;">病人</span>在发病前，都会经历很长的MUGS和SMM<span style="color: black;">周期</span>，MUGS<span style="color: black;">病人</span>和SMM<span style="color: black;">病人</span>每年<span style="color: black;">发展</span>为MM的<span style="color: black;">危害</span>大约分别为1%~2%和10%。但遗憾的是，在这两个<span style="color: black;">没</span>症状的<span style="color: black;">周期</span>，<span style="color: black;">咱们</span>并<span style="color: black;">无</span>有效的手段来阻止病情的<span style="color: black;">发展</span>，能做的<span style="color: black;">仅有</span>观察等待，在发展为MM，<span style="color: black;">显现</span>临床症状后再加以治疗。</span><span style="color: black;">幸运的是，MM是癌症中治疗效果较好的一种。它的治疗<span style="color: black;">重点</span>以<span style="color: black;"><strong style="color: blue;">免疫调节剂、蛋白酶体<span style="color: black;">控制</span>剂和皮质类固醇三类药的联合化疗</strong></span>为主，<span style="color: black;">例如</span>硼替佐米+来那度胺+地塞米松的VRd组合，一线治疗MM能有<span style="color: black;"><strong style="color: blue;">82%的缓解率</strong></span></span><span style="color: black;"><span style="color: black;"></span></span><span style="color: black;">，<span style="color: black;">没</span>论<span style="color: black;">是不是</span>进行自体造血干细胞移植，都有<span style="color: black;"><strong style="color: blue;">80%以上的4年<span style="color: black;">存活</span>率</strong></span></span><span style="color: black;"><span style="color: black;"></span></span><span style="color: black;">。</span><span style="color: black;">而在MM的<span style="color: black;"><strong style="color: blue;">二线治疗中</strong></span>，常用的<span style="color: black;">药品</span>依然是老三样的免疫调节剂、蛋白酶体<span style="color: black;">控制</span>剂和皮质类固醇，只是在这三类<span style="color: black;">药品</span>中进行不同的<span style="color: black;">摆列</span>组合，<span style="color: black;"><strong style="color: blue;"><span style="color: black;">最后</span>几乎所有<span style="color: black;">病人</span>还是会再次复发。而再次复发后，MM<span style="color: black;">病人</span>可<span style="color: black;">选取</span>的治疗<span style="color: black;">方法</span>就<span style="color: black;">非常</span>有限了。</strong></span></span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;"><strong style="color: blue;"><span style="color: black;">MM新疗法</span></strong></span></strong></span></p><span style="color: black;">近些年，MM的治疗<span style="color: black;">显现</span>了不少的新疗法，这些新疗法<span style="color: black;">重点</span>是围绕着两个治疗靶点——<span style="color: black;"><strong style="color: blue;">CD38</strong></span>和</span><span style="color: black;"><span style="color: black;"><strong style="color: blue;">BCMA</strong></span></span><span style="color: black;">。</span><span style="color: black;">CD38是MM细胞上高度且均匀表达的一种标志分子，而在正常的骨髓和淋巴细胞上表达较低，是治疗MM的一个理想靶点。<span style="color: black;">日前</span>，<span style="color: black;">已然</span>有了达雷妥尤单抗等多种治疗MM的CD38<span style="color: black;">控制</span>剂。</span><span style="color: black;">在中位接受过2种先前治疗的498名MM<span style="color: black;">病人</span>中，</span><span style="color: black;">达雷妥尤单抗+硼替佐米+地塞米松</span><span style="color: black;">的治疗<span style="color: black;">方法</span>相比硼替佐米+地塞米松，将<span style="color: black;">病人</span>的1年<span style="color: black;">没</span><span style="color: black;">发展</span><span style="color: black;">存活</span>率从26.9%<span style="color: black;">提高</span>到了<span style="color: black;"><strong style="color: blue;">60.7%</strong></span>，疗效<span style="color: black;">非常</span><span style="color: black;">显著</span></span><span style="color: black;"><span style="color: black;"></span></span><span style="color: black;">。</span><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/ZbHdNdNfVmm3IwoC7Yym8RfS58mtcorSob4ZZmicdyq60iayvYCnwF96gsYRqGYVy2OkKZVwyxwIx4APxZuFA2Yw/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">多发性骨髓瘤新疗法的靶点和相应<span style="color: black;">药品</span></span><span style="color: black;">另一个靶点BCMA全<span style="color: black;">叫作</span>叫做成熟B细胞抗原，恶性浆细胞和正常的B细胞上都有表达。靶向BCMA的疗法种类<span style="color: black;">非常多</span>，有抗体偶联<span style="color: black;">药品</span></span><span style="color: black;">（ADC）</span><span style="color: black;">，有CAR-T，还有<span style="color: black;"><strong style="color: blue;">双特异性抗体</strong></span>。</span><span style="color: black;">中国生物<span style="color: black;">机构</span>传奇生物的BCMA CAR-T疗法<span style="color: black;">日前</span>已经在美上市，客观缓解率和中位<span style="color: black;">没</span><span style="color: black;">发展</span><span style="color: black;">存活</span>期分别高达<span style="color: black;"><strong style="color: blue;">97.9%</strong></span>和</span><span style="color: black;"><span style="color: black;"><strong style="color: blue;">34.9个月</strong></span></span><span style="color: black;">，疗效<span style="color: black;">非常</span>优异</span><span style="color: black;"><span style="color: black;"></span></span><span style="color: black;">。只是<span style="color: black;">做为</span>一种CAR-T疗法，它的价格<span style="color: black;">亦</span><span style="color: black;">非常</span><span style="color: black;">昂贵</span>，定价高达46.5万美元。</span><span style="color: black;">而双特异性抗体与CAR-T疗法<span style="color: black;">能够</span>说是异曲同工，<span style="color: black;">经过</span><span style="color: black;">同期</span>靶向T细胞上的CD3分子和癌细胞上的BCMA分子，将人体<span style="color: black;">自己</span>的T细胞带去杀伤癌细胞。II期临床<span style="color: black;">实验</span>中，双特异抗体<span style="color: black;"><strong style="color: blue;">GSK2857916</strong></span>在2.5mg/<span style="color: black;">公斤</span>和3.4mg/<span style="color: black;">公斤</span>剂量组中分别<span style="color: black;">得到</span>了<span style="color: black;"><strong style="color: blue;">31%</strong></span>和</span><span style="color: black;"><span style="color: black;"><strong style="color: blue;">34%</strong></span></span><span style="color: black;">的客观缓解率</span><span style="color: black;"><span style="color: black;"></span></span><span style="color: black;">。</span><span style="color: black;"><span style="color: black;">日前</span>，国内<span style="color: black;">亦</span>有几种多发性骨髓瘤新疗法在<span style="color: black;">实验</span>之中，正在招募<span style="color: black;">病人</span>，<span style="color: black;">详细</span><span style="color: black;">状况</span>如下：</span><img src="https://mmbiz.qpic.cn/sz_mmbiz_png/ZbHdNdNfVmm3IwoC7Yym8RfS58mtcorS26HbAEY25Sic0QPYWn1RQkrhN0t0f5OOlbu2oRPriaiaYFOXJFJvoo8EQ/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">感兴趣的<span style="color: black;">病人</span><span style="color: black;">能够</span>扫描图上二维码，联系<span style="color: black;">咱们</span>进行咨询</span><span style="color: black;">参考文献：</span><span style="color: black;">. https://www.cancer.net/cancer-types/multiple-myeloma/statistics</span><span style="color: black;">. Durie B G M,
Hoering A, Abidi M H, et al. Bortezomib with lenalidomide and dexamethasone
versus lenalidomide and dexamethasone alone in patients with newly diagnosed
myeloma without intent for immediate autologous stem-cell transplant (SWOG
S0777): a randomised, open-label, phase 3 trial. The Lancet, 2017,
389(10068): 519-527.</span><span style="color: black;">. Attal M,
Lauwers-Cances V, Hulin C, et al. Autologous transplantation for multiple
myeloma in the era of new drugs: a phase III study of the Intergroupe
Francophone Du Myelome (IFM/DFCI 2009 Trial). Blood, 2015, 126(23): 391.</span><span style="color: black;">. Palumbo A,
Chanan-Khan A, Weisel K, et al. Daratumumab, bortezomib, and dexamethasone for
multiple myeloma. New England Journal of Medicine, 2016, 375(8): 754-766.</span><span style="color: black;">. Lin Y, Martin T
G, Usmani S Z, et al. CARTITUDE-1 final results: Phase 1b/2 study of
ciltacabtagene autoleucel in heavily pretreated patients with
relapsed/refractory multiple myeloma. 2023.</span><span style="color: black;">. Lonial S, Lee H
C, Badros A, et al. Belantamab mafodotin for relapsed or refractory multiple
myeloma (DREAMM-2): a two-arm, randomised, open-label, phase 2 study. The
lancet oncology, 2020, 21(2): 207-221.</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">PS.<span style="color: black;">倘若</span>你<span style="color: black;">亦</span>想<span style="color: black;">认识</span>癌后的<span style="color: black;">恢复</span>经验，欢迎扫码加入<span style="color: black;">恢复</span>经验交流群，和<span style="color: black;">更加多</span>经验丰富的病友们<span style="color: black;">一块</span>讨论～</span></p>
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