Copanlisib 治疗复发/难治性 B 细胞非霍奇金淋巴瘤的疗效和安全性：前瞻性临床试验的荟萃分析。
Efficacy and safety of copanlisib in relapsed/refractory B-cell non-Hodgkin lymphoma: A meta-analysis of prospective clinical trials.
机构信息
Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
Gastric Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
出版信息
Front Immunol. 2022 Nov 11;13:1034253. doi: 10.3389/fimmu.2022.1034253. eCollection 2022.
BACKGROUND
Copanlisib is an intravenously administered pan-class I PI3K inhibitor that has been demonstrated to have appreciable effects in the treatment of patients with lymphoma. The purpose of this meta-analysis was to evaluate the efficacy and safety of copanlisib for treating patients with relapsed/refractory (R/R) B-cell non-Hodgkin lymphoma (B-NHL).
METHODS
PubMed, Web of Science, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for relevant studies published prior to July 2022. The efficacy evaluation included complete response rate (CR), partial response rate (PR), rate of stable disease (SDR), overall response rate (ORR), disease control rate (DCR), rate of progressive disease (PDR), median progression-free survival (PFS), and median overall survival (OS). Any grade adverse events (AEs) and grade ≥3 AEs were synthesized to assess its safety.
RESULTS
Eight studies with a total of 652 patients with R/R B-NHL were identified. The pooled CR, PR, ORR, SDR, DCR, and PDR from all 8 articles were 13%, 40%, 57%, 19%, 86%, and 9%, respectively. The CR and ORR of combination therapy with rituximab were higher than those with copanlisib monotherapy for R/R B-NHL (34% vs. 6%, p<0.01; 89% vs. 42%, p<0.01). For patients with R/R indolent B-NHL, CR and ORR were lower with copanlisib monotherapy than with combination therapy with rituximab (7% vs. 34%, p<0.01; 58% vs. 92%, p<0.01). In R/R B-NHL patients receiving copanlisib monotherapy and combination therapy with rituximab, the risk of any grade AEs was 99% and 96%, respectively, and the risk of grade ≥3 AEs was 84% and 91%, respectively. The common any grade AEs included hyperglycemia (66.75%), hypertension (48.57%), diarrhea (35.06%), nausea (34.98%) and fatigue (30.33%). The common grade ≥3 AEs included hyperglycemia (45.14%), hypertension (35.07%), and neutropenia (14.75%). The comparison of AEs between the copanlisib monotherapy and the combination therapy with rituximab showed that hyperglycemia of any grade (p<0.0001), hypertension of any grade (p=0.0368), fatigue of any grade (p<0.0001), grade ≥3 hypertension (p<0.0001) and grade ≥3 hyperglycemia (p=0.0074) were significantly different between the two groups.
CONCLUSION
Our meta-analysis demonstrated that the efficacy of both copanlisib monotherapy and combination therapy with rituximab in patients with R/R B-NHL was satisfactory, while treatment-related AEs were tolerable. Compared with copanlisib monotherapy, combination therapy with rituximab showed superior efficacy for treating R/R B-NHL, and its safety was manageable.
SYSTEMATIC REVIEW REGISTRATION
https://inplasy.com/inplasy-2022-10-0008/, identifier INPLASY2022100008.
背景
Copanlisib 是一种静脉内给药的 I 类 PI3K 抑制剂，已被证明在治疗淋巴瘤患者方面具有显著效果。本荟萃分析的目的是评估 copanlisib 治疗复发/难治性（R/R）B 细胞非霍奇金淋巴瘤（B-NHL）患者的疗效和安全性。
方法
检索了截至 2022 年 7 月之前发表的相关研究，包括 PubMed、Web of Science、EMBASE 和 Cochrane 对照试验中心注册库。疗效评估包括完全缓解率（CR）、部分缓解率（PR）、疾病稳定率（SDR）、总缓解率（ORR）、疾病控制率（DCR）、进展率（PDR）、中位无进展生存期（PFS）和中位总生存期（OS）。综合分析所有 8 篇文章中任何等级的不良反应（AE）和≥3 级 AE，以评估其安全性。
结果
共纳入 8 项研究，总计 652 例 R/R B-NHL 患者。8 篇文章中汇总的 CR、PR、ORR、SDR、DCR 和 PDR 分别为 13%、40%、57%、19%、86%和 9%。与 copanlisib 单药治疗相比，联合利妥昔单抗治疗 R/R B-NHL 的 CR 和 ORR 更高（34%比 6%，p<0.01；89%比 42%，p<0.01）。对于 R/R 惰性 B-NHL 患者，copanlisib 单药治疗的 CR 和 ORR 低于联合利妥昔单抗治疗（7%比 34%，p<0.01；58%比 92%，p<0.01）。接受 copanlisib 单药和联合利妥昔单抗治疗的 R/R B-NHL 患者，任何等级 AE 的风险分别为 99%和 96%，≥3 级 AE 的风险分别为 84%和 91%。常见的任何等级 AE 包括高血糖（66.75%）、高血压（48.57%）、腹泻（35.06%）、恶心（34.98%）和疲劳（30.33%）。常见的≥3 级 AE 包括高血糖（45.14%）、高血压（35.07%）和中性粒细胞减少（14.75%）。copanlisib 单药治疗与联合利妥昔单抗治疗的 AE 比较显示，任何等级的高血糖（p<0.0001）、任何等级的高血压（p=0.0368）、任何等级的疲劳（p<0.0001）、任何等级的≥3 级高血压（p<0.0001）和任何等级的≥3 级高血糖（p=0.0074）两组之间差异均有统计学意义。
结论
本荟萃分析表明，copanlisib 单药和联合利妥昔单抗治疗 R/R B-NHL 的疗效均令人满意，而治疗相关 AE 可耐受。与 copanlisib 单药治疗相比，联合利妥昔单抗治疗 R/R B-NHL 的疗效更优，其安全性可控。
系统评价注册
https://inplasy.com/inplasy-2022-10-0008/，标识符 INPLASY2022100008。
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