TY - JOUR
T1 - Ixazomib, daratumumab and low-dose dexamethasone in intermediate-fit patients with newly diagnosed multiple myeloma
T2 - an open-label phase 2 trial
AU - Groen, Kaz
AU - Stege, Claudia A. M.
AU - Nasserinejad, Kazem
AU - de Heer, Koen
AU - van Kampen, Roel J. W.
AU - Leys, Rineke B. L.
AU - Thielen, Noortje
AU - Westerman, Matthijs
AU - Wu, Ka-Lung
AU - Ludwig, Inge
AU - Issa, Djamila E.
AU - Velders, Gerjo A.
AU - Vekemans, Marie-Christiane
AU - Timmers, Gert-Jan
AU - de Boer, Fransien
AU - Tick, Lidwine W.
AU - Verbrugge, Annelies
AU - Buitenhuis, Danny
AU - Cunha, Sonia M.
AU - van der Spek, Ellen
AU - de Waal, Esther G. M.
AU - Sohne, Maaike
AU - Sonneveld, Pieter
AU - Nijhof, Inger S.
AU - Klein, Saskia K.
AU - van de Donk, Niels W. C. J.
AU - Levin, Mark-David
AU - Ypma, Paula F.
AU - Zweegman, Sonja
N1 - Funding Information:
Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.
Publisher Copyright:
© 2023 The Author(s)
PY - 2023/9/1
Y1 - 2023/9/1
N2 - 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. Funding: Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.
AB - 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. Funding: Janssen Pharmaceuticals, Takeda Pharmaceutical Company Limited.
KW - Daratumumab
KW - Elderly
KW - IMWG frailty index
KW - Intermediate-fit
KW - Ixazomib
KW - Multiple myeloma
UR - https://www.scopus.com/pages/publications/85169037609
U2 - 10.1016/j.eclinm.2023.102167
DO - 10.1016/j.eclinm.2023.102167
M3 - Article
C2 - 37680948
SN - 2589-5370
VL - 63
JO - EClinicalMedicine
JF - EClinicalMedicine
M1 - 102167
ER -