口服核输出选择性抑制剂塞利尼索在弥漫性大B细胞淋巴瘤亚型中的有效性和安全性比较

Comparison of the Effectiveness and Safety of the Oral Selective Inhibitor of Nuclear Export, Selinexor, in Diffuse Large B Cell Lymphoma Subtypes.

作者信息

Casasnovas Rene-Olivier, Follows George, Zijlstra Josee M, Vermaat Joost S P, Kalakonda Nagesh, Choquet Sylvain, Neste Eric Van Den, Hill Brian, Thieblemont Catherine, Cavallo Federica, la Cruz Fatima De, Kuruvilla John, Hamad Nada, Jaeger Ulrich, Caimi Paolo F, Gurion Ronit, Warzocha Krzysztof, Bakhshi Sameer, Sancho Juan-Manuel, Schuster Michael, Egyed Miklos, Offner Fritz, Vassilakopoulos Theodoros P, Samal Priyanka, Ku Matthew, Ma Xiwen, Chamoun Kamal, Shah Jatin, Canales Miguel, Maerevoet Marie, Shacham Sharon, Kauffman Michael G, Goy Andre

机构信息

Hématologie Clinique and INSERM 1231, CHU Dijon Bourgogne, Dijon, France.

Addenbrooke's Hospital, Cambridge, United Kingdom.

出版信息

Clin Lymphoma Myeloma Leuk. 2022 Jan;22(1):24-33. doi: 10.1016/j.clml.2021.07.017. Epub 2021 Jul 22.

DOI:10.1016/j.clml.2021.07.017

PMID:34493477

Abstract

BACKGROUND

The SADAL study evaluated oral selinexor in patients with relapsed and/or refractory diffuse large B-cell lymphoma (DLBCL) after at least 2 prior lines of systemic therapy. In this post-hoc analysis, we analyzed the outcomes of the SADAL study by DLBCL subtype to determine the effects of DLBCL subtypes on efficacy and tolerability of selinexor.

PATIENTS AND METHODS

Data from 134 patients in SADAL were analyzed by DLBCL subtypes for overall response rate (ORR), overall survival (OS), duration of treatment response, progression-free survival, and adverse events rate.

RESULTS

ORR in the entire cohort was 29.1%, and similar in patients with germinal center (GCB) versus non-GCB DLBCL (31.7% vs. 24.2%, P = 0.45); transformed DLBCL showed a trend towards higher ORR than de novo DLBCL: 38.7% vs. 26.2% (P = 0.23). Despite similar prior treatment regimens and baseline characteristics, patients with DLBCL and normal C-MYC/BCL-2 protein expression levels had a significantly higher ORR (46.2% vs.14.8%, P = 0.012) and significantly longer OS (medians 13.7 vs. 5.1 months, hazard ratio 0.43 [95% CI, 0.23-0.77], P = 0.004) as compared with those whose DLBCL had C-MYC and BCL-2 overexpression. Among patients who had normal expression levels of either C-MYC or BCL-2 and baseline hemoglobin levels ≥ 10g/dL, ORR was 51.5% (n = 47), with median OS of 15.5 months and median PFS of 4.6 months. Similar rates of adverse events were noted in all subgroups.

CONCLUSIONS

Overall, single agent oral selinexor showed strong responses in patients with limited treatment alternatives regardless of germinal center B-cell type or disease origin.

摘要

背景

SADAL研究评估了口服塞利尼索在至少接受过2线全身治疗的复发和/或难治性弥漫性大B细胞淋巴瘤（DLBCL）患者中的疗效。在这项事后分析中，我们按DLBCL亚型分析了SADAL研究的结果，以确定DLBCL亚型对塞利尼索疗效和耐受性的影响。

患者和方法

对SADAL研究中134例患者的数据按DLBCL亚型分析总缓解率（ORR）、总生存期（OS）、治疗反应持续时间、无进展生存期和不良事件发生率。

结果

整个队列的ORR为29.1%，生发中心（GCB）型与非GCB型DLBCL患者的ORR相似（31.7%对24.2%，P = 0.45）；转化型DLBCL的ORR有高于初发型DLBCL的趋势：38.7%对26.2%（P = 0.23）。尽管既往治疗方案和基线特征相似，但DLBCL患者C-MYC/BCL-2蛋白表达水平正常者的ORR显著更高（46.2%对14.8%，P = 0.012），OS显著更长（中位数分别为13.7个月和5.1个月，风险比0.43 [95% CI，0.23 - 0.77]，P = 0.004），而DLBCL伴有C-MYC和BCL-2过表达的患者则不然。在C-MYC或BCL-2表达水平正常且基线血红蛋白水平≥10g/dL的患者中，ORR为51.5%（n = 47），OS中位数为15.5个月，PFS中位数为4.6个月。所有亚组的不良事件发生率相似。