A simplified frailty scale predicts outcomes in transplant-ineligible patients with newly diagnosed multiple myeloma treated in the FIRST (MM-020) trial

Thierry Façon ,Meletios A Dimopoulos,Bruno Costa,Jean Yves Mary,Michael Sturniolo,Mohamad Mohty,Nathalie Meuleman,Antoine Tinel,Marie Lorraine Chrétien ,Eileen M Boyle ,Xavier Leleu,Cyrille Hulin,Shien Guo,Andrew Belch,Philippe Moreau,Wen Ming Chen ,Mara Silvia Monzini,Salomon Manier,Adrian Tempescul,Michel Attal,Kihyun Kım ,Heinz Ludwig,Paula Rodríguez‐Otero ,Vanessa Houck,Margaret Macro,William Renwick,Elena Zamagni,Christian Rosé

doi:10.1038/s41375-019-0539-0

Abstract

Patients with multiple myeloma are generally older and vary in fitness levels, which may influence the clinical benefit of treatment. Patients from the large, phase 3 FIRST trial in newly diagnosed multiple myeloma (NDMM) were retrospectively investigated to determine outcomes based on frailty using scores for age, Charlson Comorbidity Index (CCI), and Eastern Cooperative Oncology Group performance status (ECOG PS), instead of the EQ-5D quality-of-life questionnaire, as previously reported. ECOG PS (n = 1618) was investigated in frailty groups: frail (49%) and nonfrail (51%). Frail patients experienced worse progression-free and overall survival vs nonfrail patients. Prognostic assessment was improved when combining frailty and International Staging System stage (I/II vs III). Frail patients had a higher risk of developing grade 3/4 treatment-emergent adverse events. Treatment effects observed in the FIRST trial were confirmed per frailty group and per frailty and ISS group. The use of this ECOG PS–containing frailty scale as a predictive measure of clinical outcomes in patients with transplant-ineligible NDMM is supported by data from the FIRST trial. This score, based on age, CCI, and ECOG PS, can be easily replicated and may help design future myeloma studies in frail or nonfrail elderly patients.

Highlights

Multiple myeloma is predominantly a disease of the elderly, with a median age of 69 years at diagnosis [1]
One feature of Similar to the International Myeloma Working group (IMWG) frailty scale [4], the frailty scale described here analyzed transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM) and was able to predict progression-free survival (PFS) and overall survival (OS) outcomes
Subdividing fitness categories by International Staging System (ISS) stage at diagnosis increased the prognostic value of the frailty scale, which is consistent with what was observed with the IMWG frailty scale

Summary

Introduction

Multiple myeloma is predominantly a disease of the elderly, with a median age of 69 years at diagnosis [1]. Treatment with newer agents has improved survival outcomes for patients with newly diagnosed multiple myeloma (NDMM) [2, 3], especially among those >65 years of age [3]. Elderly patients are a heterogeneous population that varies greatly in fitness levels, with frail patients often underrepresented in clinical trials. In Memoriam to Professor Dr Christian Rose

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Results

Conclusion