[ASCO 2017]Elotuzumab联合RVD方案治疗骨髓瘤，毒性显著

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2017年6月2-6日，一年一度的美国临床肿瘤学会（ASCO）年会已在芝加哥成功举办。当地时间6月5日上午的多发性骨髓瘤专场上，研究人员报道了一项摘要号为8002的开放性、单中心IIa期研究初步结果。对于初治多发性骨髓瘤（MM）患者而言，elotuzumab联合硼替佐米、来那度胺和地塞米松方案（elo RVD）毒性显著，感染风险大。

来自波士顿的Jacob Laubach教授表示，elotuzumab联合RVD方案治疗初治多发性骨髓瘤（MM）达到的总体反应率与之前报道的RVD方案相近。有超过预期的患者数（6/40，15%）因不良事件在前4个疗程内停止治疗。总体而言，感染发生率为50%，其中包括1例5级脓毒症，1例4级败血症和4例3级或3级以上的肺部感染。

Laubach教授表示，虽然不良反应发生率较高，但接受至少4个周期治疗后的患者总体反应率较为可观。通过调整剂量和给药时间可能会改善毒性反应。

Elotuzumab是一种靶向细胞表面蛋白SLAMF7（它存在于骨髓瘤细胞和NK细胞）的单克隆抗体。它通过直接靶向骨髓瘤细胞、增加NK细胞杀伤骨髓瘤细胞的能力，提供了对癌症的双重攻击。该药单药治疗复发/难治性MM的活性并不显著，但与其他抗肿瘤药物（如硼替佐米或来那度胺）联合应用时，抗骨髓瘤活性非常显著，改善了患者的反应率和临床预后。

该研究评估了4个周期的elotuzumab +来那度胺、硼替佐米和地塞米松对适宜移植的初治MM患者的安全性和有效性。

初治MM患者在接受了4个周期的ELO-RVD方案诱导治疗和干细胞动员后，立即进行了自体造血干细胞移植（ASCT）或4个周期的ELO-RVD治疗。后期的维持治疗包括28天为1周期的ELO RVD方案治疗高危患者（如ISS分期III和/或具有高危细胞遗传学），或者elotuzumab、来那度胺和地塞米松治疗标危患者（ISS分期I或II，且无高危细胞遗传学），直至疾病进展。

4个周期的治疗结束后，33/40例患者获得部分或完全缓解，总缓解率为82%。至首次缓解的中位时间为25天，分析时尚未达到中位缓解时间。半数（50%）未行ASCT的患者以及90%的接受了ASCT的患者在分析时仍在治疗中。

最常见的不良事件包括疲劳（60%）、神经病变（55%）、肌肉骨骼和关节疼痛（55%）、感染（50%）、背部或颈部疼痛（48%）和腹泻（45%）等。3级或3级以上的血液学不良事件包括血小板减少（10%）、贫血（5%）、发热性中性粒细胞减少（5%）、淋巴细胞减少（2%）和中性粒细胞减少（2%）。最常见的3级或3级以上非血液学不良事件包括低磷血症（12%）、疲劳（10%）、肺部感染（10%）、高血压（10%）、ALT升高（5%）和晕厥（5%）。

该研究中，2例患者死亡，其中1例在2个周期治疗后死于败血症和呼吸衰竭，另1例因发热性中性粒细胞减少、脓毒症相关性低血压和之后的肾衰竭入院接受了1周的治疗，但停药后30天死亡。另外，研究小组还报道了4级的血小板减少症（5%）、高血糖（2%）、心搏停止（2%）和呼吸衰竭（2%）。另有5例患者在治疗停止后出现了毒性反应，包括周围神经病变、情绪障碍、高血糖、直立性低血压、多发性神经病变和肺部感染。

摘要原文

An open-label, single arm, phase IIa study of bortezomib, lenalidomide, dexamethasone, and elotuzumab in newly diagnosed multiple myeloma.

Background: Elotuzumab (elo) is approved for use in combination with lenalidomide (len) and dexamethasone (dex) for relapsed and refractory multiple myeloma (MM). This phase 2a study evaluated the efficacy and safety of elo in combination with len, subcutaneous bortezomib (bortez), and dex. 

Methods: The primary objective of this study was to determine the response rate of newly diagnosed, transplant-eligible MM patients (pts) after four cycles of therapy with elo plus len, bortez, and dex. Pts were newly diagnosed with MM by the revised IMWG criteria. Elo was administered days 1, 8, and 15 of the first two 28 day cycles and days 1 and 11 in cycles 3 and 4. Following cycle 4, pts underwent stem cell mobilization and could then proceed with either autologous stem cell transplant (ASCT) or defer transplant and receive four more cycles of induction therapy with elo plus len, bortez, and dex. Following either ASCT or 8 cycles of induction chemotherapy, pts transitioned to risk-adapted maintenance with elo, len, and dex plus every other week bortez (pts with high-risk cytogenetics, ISS stage II or III) or elo, len, dex (all others). Responses were assessed by the modified Uniform Response Criteria and toxicities graded based on NCI-CTCAE V4. 

Results: 41 patients with a median age of 60 were enrolled and this analysis encompasses response data from 29 patients. The overall response rate (ORR) after four cycles was 100%, with 24% achieving a complete response (CR), 47% achieving a very good partial response (VGPR), and 29% a partial response (PR). The rate of VGPR or better was 71%. The median number of CD34+ stem cells collected was 10.3 x 10^6. The most frequent grade 3 or higher toxicities included thrombocytopenia (15%) and hypophosphatemia (12%). The rate of grade 3 or higher peripheral neuropathy was 2%. Two pts died while on study, one due to complications of septicemia and the other due to respiratory failure. 

Conclusions: The combination of elo plus len, bortez, and dex was effective in newly diagnosed, ASCT-eligible patients. The rate of high-grade toxicities was low, although there were two grade 5 events (septicemia and respiratory failure). Clinical trial information: NCT02375555

医脉通编译自：Significant Toxicity, Infection Risk Associated With Elo-RVD in Myeloma.CancerNetwork.2017