Gasparetto Cristina, Lentzsch Suzanne, Schiller Gary, Callander Natalie, Tuchman Sascha, Chen Christine, White Darrell, Kotb Rami, Sutherland Heather, Sebag Michael, Baljevic Muhamed, Bensinger William, LeBlanc Richard, Venner Chris, Bahlis Nizar, Rossi Adriana, Biran Noa, Sheehan Heidi, Saint-Martin Jean-Richard, Van Domelen Dane, Kai Kazuharu, Shah Jatin, Shacham Sharon, Kauffman Michael, Lipe Brea
Duke Cancer Institute School of Medicine Duke University Durham North Carolina.
Columbia University New York New York.
EJHaem. 2020 Nov 8;2(1):56-65. doi: 10.1002/jha2.122. eCollection 2021 Feb.
We assessed the safety, efficacy, maximum tolerated dose (MTD), and the recommended phase 2 dose (RP2D) of selinexor, a first in class oral selective inhibitor of nuclear export (100 mg once weekly [QW] or 60 mg twice weekly), in combination with daratumumab (16 mg/kg per label) and dexamethasone (40 mg QW) (SDd) in patients with relapsed refractory multiple myeloma (RRMM). Thirty-four patients (median prior therapies, 3 [range, 2-10]) were enrolled; MM was refractory to proteasome inhibitor (PI) in 85%, immunomodulatory agent (IMiD) in 76%, both in 74%, and daratumumab in 6% of patients. Two dose-limiting toxicities (DLTs) were reported in the selinexor 60 mg twice-weekly cohort with no DLTs in the 100 mg QW cohort, making 100 mg QW the MTD and RP2D. Common treatment-related adverse events included thrombocytopenia (70.6%), nausea (70.6%), fatigue (61.8%), anemia (61.8%), and neutropenia (50.0%). Overall response rate was 73% and median progression-free survival 12.5 months in daratumumab-naïve patients. SDd was well tolerated and its promising efficacy suggests that further study of this PI- and IMiD-free regimen in RRMM patients who had at least one prior line of therapy including a PI and an IMiD but whose disease is naïve to daratumumab is warranted.
我们评估了塞利尼索（一种一流的口服选择性核输出抑制剂，每周一次100毫克或每周两次60毫克）与达雷妥尤单抗（每标签16毫克/千克）和地塞米松（每周一次40毫克）（SDd）联合使用时，在复发难治性多发性骨髓瘤（RRMM）患者中的安全性、疗效、最大耐受剂量（MTD）和推荐的2期剂量（RP2D）。34名患者（既往治疗的中位数为3次[范围2 - 10次]）入组；85%的患者MM对蛋白酶体抑制剂（PI）难治，76%对免疫调节剂（IMiD）难治，74%对两者均难治，6%的患者对达雷妥尤单抗难治。在塞利尼索每周两次60毫克队列中报告了2例剂量限制性毒性（DLT），而每周一次100毫克队列中未出现DLT，因此每周一次100毫克为MTD和RP2D。常见的治疗相关不良事件包括血小板减少（70.6%）、恶心（70.6%）、疲劳（61.8%）、贫血（61.8%）和中性粒细胞减少（50.0%）。在未使用过达雷妥尤单抗的患者中，总体缓解率为73%，中位无进展生存期为12.5个月。SDd耐受性良好，其有前景的疗效表明，对于至少接受过包括PI和IMiD在内的一线治疗但疾病对达雷妥尤单抗初治的RRMM患者，对这种不含PI和IMiD的方案进行进一步研究是有必要的。
