Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials

Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of...

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Autores principales:	Yali Tao, Hui Zhou, Ting Niu
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	selinexor multiple myeloma XPO1 efficacy safety meta-analysis Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/37a607ca8f494058be4a4103afc2ef22
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spelling	oai:doaj.org-article:37a607ca8f494058be4a4103afc2ef222021-12-03T06:25:49ZSafety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials1663-981210.3389/fphar.2021.758992https://doaj.org/article/37a607ca8f494058be4a4103afc2ef222021-12-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fphar.2021.758992/fullhttps://doaj.org/toc/1663-9812Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p < 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p < 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p < 0.00001), nausea (72 vs 52%, p < 0.00001), vomiting (41 vs 23%, p < 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p < 0.0001) than SEL + DEX treatment in grade≥3 AEs.Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.Yali TaoHui ZhouTing NiuFrontiers Media S.A.articleselinexormultiple myelomaXPO1efficacysafetymeta-analysisTherapeutics. PharmacologyRM1-950ENFrontiers in Pharmacology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	selinexor multiple myeloma XPO1 efficacy safety meta-analysis Therapeutics. Pharmacology RM1-950
spellingShingle	selinexor multiple myeloma XPO1 efficacy safety meta-analysis Therapeutics. Pharmacology RM1-950 Yali Tao Hui Zhou Ting Niu Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials
description	Background: Selinexor (SEL) is an orally bioavailable, highly-selective, and slowly-reversible small molecule that inhibits Exportin 1. Preclinical studies showed that SEL had synergistic antimyeloma activity with glucocorticoids, proteasome inhibitors (PIs) and immunomodulators. The combination of selinexor and dexamethasone (DEX) has been approved in the United States for patients with penta-refractory multiple myeloma in July 2019. This meta-analysis aimed to investigate the safety and efficacy of selinexor based treatment in Multiple myeloma.Methods: We systematically searched the Medline (PubMed), Embase, Web of Science, Cochrane Central Register of Controlled Trials Library databases and ClinicalTrials.gov. Outcome measures of efficacy included overall response rate (ORR), clinical benefit rate (CBR), stringent complete response rate (sCR), complete response rate (CR), very good partial response (VGPR), partial response rate (PR), minimal response (MR), rate of stable disease (SDR), rate of progressive disease (PDR) and median progression-free survival (mPFS). Safety was evaluated by the incidences of all grade adverse events and Grade≥3 adverse events. The subgroup analysis was conducted to analyze the difference in different combination treatment regimens (SEL + DEX + PIs vs SEL + DEX).Results: We included six studies with 477 patients. The pooled ORR, CBR, sCR, CR, VGPR, PR, MR, SDR, and PDR were 43% (18–67%), 55% (32–78%), 5% (−2–13%), 7% (4–11%), 14% (5–24%), 23% (15–31%), 11% (8–14%), 26% (14–38%) and 14% (4–23%), respectively. SEL + DEX + PIs treatment had higher ORR (54 vs 24%, p = 0.01), CBR (66 vs 37%, p = 0.01), sCR (10 vs 2%, p = 0.0008), and VGPR (23 vs 5%, p < 0.00001) compared to SEL + DEX treatment, and lower PDR (4 vs 23%, p < 0.00001) and SDR (17 vs 37%, p = 0.0006). The pooled incidences of any grade and grade≥3 were 45 and 30% in hematological AEs, and in non-hematological AEs were 40 and 30%, respectively. The most common all grade (68%) and grade≥3 (54%) hematological AE were both thrombocytopenia. Fatigue was the most common all grade (62%) and grade≥3 (16%) non-hematological AE. Compared to SEL + DEX treatment, SEL + DEX + PIs treatment had lower incidences of hyponatremia (39 vs 12%, p < 0.00001), nausea (72 vs 52%, p < 0.00001), vomiting (41 vs 23%, p < 0.0001), and weight loss (42 vs 17%, p = 0.03) in all grade AEs. Meanwhile, SEL + DEX + PIs treatment had lower incidences of anemia (36 vs 16%, p = 0.02), fatigue (20 vs 13%, p = 0.04), hyponatremia (22 vs 5%, p < 0.0001) than SEL + DEX treatment in grade≥3 AEs.Conclusion: Our meta-analysis revealed that selinexor-based regimens could offer reasonable efficacy and tolerable adverse events in patients with multiple myeloma. SEL + DEX + PIs treatments had higher efficacy and lower toxicities than SEL + DEX.
format	article
author	Yali Tao Hui Zhou Ting Niu
author_facet	Yali Tao Hui Zhou Ting Niu
author_sort	Yali Tao
title	Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials
title_short	Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials
title_full	Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials
title_fullStr	Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials
title_full_unstemmed	Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials
title_sort	safety and efficacy analysis of selinexor-based treatment in multiple myeloma, a meta-analysis based on prospective clinical trials
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/37a607ca8f494058be4a4103afc2ef22
work_keys_str_mv	AT yalitao safetyandefficacyanalysisofselinexorbasedtreatmentinmultiplemyelomaametaanalysisbasedonprospectiveclinicaltrials AT huizhou safetyandefficacyanalysisofselinexorbasedtreatmentinmultiplemyelomaametaanalysisbasedonprospectiveclinicaltrials AT tingniu safetyandefficacyanalysisofselinexorbasedtreatmentinmultiplemyelomaametaanalysisbasedonprospectiveclinicaltrials
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Safety and Efficacy Analysis of Selinexor-Based Treatment in Multiple Myeloma, a Meta-Analysis Based on Prospective Clinical Trials

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