Frail subgroups determine heterogeneous outcomes in older patients with NDMM: long-term follow-up of the HOVON 143 trial

Frailty, rather than age alone, is a key determinant of outcomes in older patients with multiple myeloma (MM), yet frailty assessments are often lacking in clinical trials. Consequently, data on the efficacy and tolerability of novel treatments in frail patients remain scarce. Moreover, there is substantial heterogeneity among frail patients, with some classified as frail solely due to age (>80 years) and others due to geriatric impairments and/or comorbidities. To our knowledge, the HOVON 143 trial was the first trial that was specifically designed for frail patients with newly diagnosed MM (NDMM) using the International Myeloma Working Group Frailty Index (IMWG-FI). After a median follow-up of >5 years, we report the long-term progression-free survival (PFS) and overall survival (OS) outcomes, with detailed analyses of frail subgroups. Patients who were classified as frail according to the IMWG-FI were treated with 9 induction cycles of ixazomib, daratumumab, and low-dose dexamethasone, followed by maintenance therapy until progression for a maximum of 2 years. Median PFS was 13.8 months, and median OS was 34.0 months. However, frail subgroup analyses based on geriatric impairments and comorbidities besides age revealed pronounced heterogeneity in outcomes. Both early relapse-related and nonrelapse-related mortality rates were higher in ultrafrail patients and patients who were frail due to impairments than in patients who were frail based on age alone. These findings highlight the need for a more precise frailty definition to identify patients at the highest risk of early mortality. This trial was registered at www.clinicaltrialsregister.eu as EudraCT #2016-002600-90.

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Journal
Blood Advances
Published
2025-08-22
DOI
https://doi.org/10.1182/bloodadvances.2025017394
Citations
1
Primary Topic
Frailty in Older Adults
Type
article
Field-Weighted Citation Impact
1.22

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article

Frail subgroups determine heterogeneous outcomes in older patients with NDMM: long-term follow-up of the HOVON 143 trial

Mark‐David Levin, Roel J.W. van Kampen, Maarten R. Seefat, Febe Smits et al.
1 citations
Blood Advances
Frailty in Older Adults
1.22
article

Frail subgroups determine heterogeneous outcomes in older patients with NDMM: long-term follow-up of the HOVON 143 trial

Mark‐David Levin, Roel J.W. van Kampen, Maarten R. Seefat, Febe Smits, Nazik Durdu-Rayman, Esther G.M. De Waal, Alain Kentos, Niels W.C.J. van de Donk, Claudia A.M. Stege, Paula F. Ypma, Yorick Sandberg, Marie‐Christiane Vekemans, Noortje Thielen, Ellen van der Spek, Kazem Nasserinejad, Koen de Heer, Inger S. Nijhof, Inge Ludwig, Matthijs Westerman, Yavuz M. Bilgin, Nicole C.H.P. de Graauw, Sonja Zweegman, Gert-Jan Timmers, Josien C. Regelink, Kaz Groen
article en
1 citations

Abstract

Frailty, rather than age alone, is a key determinant of outcomes in older patients with multiple myeloma (MM), yet frailty assessments are often lacking in clinical trials. Consequently, data on the efficacy and tolerability of novel treatments in frail patients remain scarce. Moreover, there is substantial heterogeneity among frail patients, with some classified as frail solely due to age (>80 years) and others due to geriatric impairments and/or comorbidities. To our knowledge, the HOVON 143 trial was the first trial that was specifically designed for frail patients with newly diagnosed MM (NDMM) using the International Myeloma Working Group Frailty Index (IMWG-FI). After a median follow-up of >5 years, we report the long-term progression-free survival (PFS) and overall survival (OS) outcomes, with detailed analyses of frail subgroups. Patients who were classified as frail according to the IMWG-FI were treated with 9 induction cycles of ixazomib, daratumumab, and low-dose dexamethasone, followed by maintenance therapy until progression for a maximum of 2 years. Median PFS was 13.8 months, and median OS was 34.0 months. However, frail subgroup analyses based on geriatric impairments and comorbidities besides age revealed pronounced heterogeneity in outcomes. Both early relapse-related and nonrelapse-related mortality rates were higher in ultrafrail patients and patients who were frail due to impairments than in patients who were frail based on age alone. These findings highlight the need for a more precise frailty definition to identify patients at the highest risk of early mortality. This trial was registered at www.clinicaltrialsregister.eu as EudraCT #2016-002600-90.

Blood AdvancesVol. 9(22)
Cliniques Universitaires Saint-Luc (BE), Dutch Cancer Society (NL), Erasmus MC (NL), Medisch Centrum Leeuwarden (NL), Albert Schweitzer Ziekenhuis (NL), Northwest Hospital (US), St. Antonius Ziekenhuis (NL), Diakonessenhuis hospital (NL), Hôpital de Jolimont (BE), Amsterdam Neuroscience (NL), Maasstad Ziekenhuis (NL), Flevoziekenhuis (NL), Zuyderland Medisch Centrum (NL), Haga Hospital (NL), Ziekenhuis Amstelland (NL), Franciscus Vlietland (NL), Admiraal De Ruyter Ziekenhuis (NL), Amsterdam University Medical Centers (NL), Rijnstate Hospital (NL), Ziekenhuis Bernhoven (NL), Meander Medisch Centrum (NL), Bravis Ziekenhuis (NL), AZ Sint-Lucas (BE), Vrije Universiteit Amsterdam (NL)
Amgen, Bristol-Myers Squibb, Pfizer, GlaxoSmithKline, Sanofi, Celgene, Regeneron Pharmaceuticals, BeiGene, Janssen Pharmaceuticals, Cilag
Openalex Percentile: Top 19%
Frailty in Older Adults
1.22
DOIOpen Access PDFOpenAlex
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