Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma: an open-label phase 2 trial

被引：6

作者：

Groen, Kaz ^{[1
,2
]}

Stege, Claudia A. M. ^{[1
,2
]}

Nasserinejad, Kazem ^{[3
,4
]}

de Heer, Koen ^{[5
]}

van Kampen, Roel J. W. ^{[6
]}

Leys, Rineke B. L. ^{[7
]}

Thielen, Noortje ^{[8
]}

Westerman, Matthijs ^{[9
]}

Wu, Ka-Lung ^{[10
]}

Ludwig, Inge ^{[11
]}

Issa, Djamila E. ^{[12
]}

Velders, Gerjo A. ^{[13
]}

Vekemans, Marie-Christiane ^{[14
]}

Timmers, Gert-Jan ^{[15
]}

de Boer, Fransien ^{[16
]}

Tick, Lidwine W. ^{[17
]}

Verbrugge, Annelies ^{[3
]}

Buitenhuis, Danny ^{[3
]}

Cunha, Sonia M. ^{[3
]}

van der Spek, Ellen ^{[18
]}

de Waal, Esther G. M. ^{[19
]}

Sohne, Maaike ^{[20
]}

Sonneveld, Pieter ^{[21
]}

Nijhof, Inger S. ^{[20
]}

Klein, Saskia K. ^{[22
,23
]}

van der Donk, Niels W. C. J. ^{[1
,2
]}

Levin, Mark-David ^{[24
]}

Ypma, Paula F. ^{[25
]}

Zweegman, Sonja ^{[1
,2
,26
]}

机构：

[1] Vrije Univ Amsterdam, Dept Hematol, Amsterdam UMC, Amsterdam, Netherlands

[2] Canc Ctr Amsterdam, Treatment & Qual Life, Amsterdam, Netherlands

[3] Erasmus MC Canc Inst, HOVON Data Ctr, Dept Hematol, Rotterdam, Netherlands

[4] Cytel Inc, Therapeut Dev Team, Innovat Stat Consulting, Waltham, MA USA

[5] Flevoziekenhuis, Dept Internal Med, Almere, Netherlands

[6] Zuyderland Hosp, Dept Internal Med, Sittard Geleen, Netherlands

[7] Maasstad Hosp, Dept Internal Med, Rotterdam, Netherlands

[8] Diakonessen Hosp, Dept Internal Med, Utrecht, Netherlands

[9] Northwest Clin, Dept Internal Med, Alkmaar, Netherlands

[10] ZNA Stuivenberg, Dept Hematol, Antwerp, Belgium

[11] Ziekenhuis Bernhoven, Dept Internal Med, Uden, Netherlands

[12] Jeroen Bosch Hosp, Dept Internal Med, Den Bosch, Netherlands

[13] Gelderse Vallei, Dept Internal Med, Ede, Netherlands

[14] UCL, Dept Hematol, Clin Univ St Luc, Brussels, Belgium

[15] Amstelland Hosp, Dept Internal Med, Amstelveen, Netherlands

[16] Ikazia Hosp, Dept Internal Med, Rotterdam, Netherlands

[17] Maxima Med Ctr, Dept Internal Med, Eindhoven, Netherlands

[18] Rijnstate Hosp, Dept Internal Med, Arnhem, Netherlands

[19] Med Ctr Leeuwarden, Dept Internal Med, Leeuwarden, Netherlands

[20] Antonius Ziekenhuis, Dept Internal Med, Nieuwegein, Netherlands

[21] Erasmus MC Canc Inst, Dept Hematol, Rotterdam, Netherlands

[22] Meander Med Ctr, Dept Internal Med, Amersfoort, Netherlands

[23] Univ Med Ctr Groningen, Dept Hematol, Groningen, Netherlands

[24] Albert Schweitzer Hosp, Dept Internal Med, Dordrecht, Netherlands

[25] Haga Hosp, Dept Internal Med, The Hague, Netherlands

[26] Dept Hematol, Boelelaan 1117, NL-1081 HV Amsterdam, Netherlands

来源：

ECLINICALMEDICINE | 2023年 / 63卷

关键词：

Multiple myeloma; Elderly; Daratumumab; Ixazomib; Intermediate-fit; IMWG frailty index; STEM-CELL TRANSPLANTATION; ORAL IXAZOMIB; LENALIDOMIDE; MAINTENANCE; BORTEZOMIB; SURVIVAL; THALIDOMIDE; PREDNISONE; MELPHALAN; CONSENSUS;

D O I：

10.1016/j.eclinm.2023.102167

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background The outcome of non-transplant eligible newly diagnosed multiple myeloma (NDMM) patients is heterogeneous, partly depending on frailty level. The aim of this study was to prospectively investigate the efficacy and safety of Ixazomib-Daratumumab-low-dose dexamethasone (Ixa-Dara-dex) in NDMM intermediate-fit patients. Methods In this phase II multicenter HOVON-143 study, IMWG Frailty index based intermediate-fit patients, were treated with 9 induction cycles of Ixa-Dara-dex, followed by maintenance with ID for a maximum of 2 years. The primary endpoint was overall response rate on induction treatment. Patients were included from October 2017 until May 2019. Trial Registration Number: NTR6297. Findings Sixty-five patients were included. Induction therapy resulted in an overall response rate of 71%. Early mortality was 1.5%. At a median follow-up of 41.0 months, median progression-free survival (PFS) was 18.2 months and 3-year overall survival 83%. Discontinuation of therapy occurred in 77% of patients, 49% due to progression, 9% due to toxicity, 8% due to incompliance, 3% due to sudden death and 8% due to other reasons. Dose modifications of ixazomib were required frequently (37% and 53% of patients during induction and maintenance, respectively), mainly due to, often low grade, polyneuropathy. During maintenance 23% of patients received daratumumab alone. Global quality of life (QoL) improved significantly and was clinically relevant, which persisted during maintenance treatment. Interpretation Ixazomib-Daratumumab-low-dose dexamethasone as first line treatment in intermediate -fit NDMM patients is safe and improves global QoL. However, efficacy was limited, partly explained by ixazomib-induced toxicity, hampering long term tolerability of this 3-drug regimen. This highlights the need for more efficacious and tolerable regimens improving the outcome in vulnerable intermediate -fit patients.

引用

页数：12

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