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

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.

Conflict of interest statement

TF has received fees for a consulting/advisory role from Amgen, Celgene, Janssen, Karyopharm, PharmaMar, and Takeda; and speakers bureau fees from Amgen, Celgene, Janssen, and Takeda. MAD reports honoraria from Amgen, Novartis, Celgene, Takeda, Genesis Pharmaceuticals, Janssen-Cilag, and Bristol-Myers Squibb; a consulting/advisory role for Amgen, Janssen-Cilag, Takeda, and Celgene; research funding from Janssen-Cilag and Amgen; and travel accommodations from Janssen-Ortho, Genesis Pharmaceuticals, and Amgen. AB, NM, W-MC, KK, CR, SM, MA, XL, MLC, JYM, and SG have nothing to report. MM has received honoraria from Celgene, Janssen, Bristol-Myers Squibb, Takeda, Novartis, and Amgen; fees for a consulting/advisory role from Celgene, Janssen, Bristol-Myers Squibb, Takeda, Novartis, and Amgen; speakers bureau fees from Janssen and Sanofi; research funding from Sanofi; and travel accommodations/expenses from Sanofi, JAZZ, Novartis, Janssen, and Amgen. EZ reports honoraria and speakers bureau fees from Celgene, Janssen, and Amgen. PR-O reports honoraria and speakers bureau fees from Celgene, Janssen, MSD, and Bristol-Myers Squibb. WR reports honoraria from Celgene, travel from Amgen, and speakers bureau fees from Bayer. AT reports export board committee for Gilead. EB has received fees for a consulting/advisory role from Celgene. PM has received honoraria from Celgene, Takeda, Novartis, Amgen, and Janssen-Cilag; and fees for a consulting/advisory role from Celgene, Takeda, Novartis, Amgen, and Janssen. MM reports honoraria from Celgene, Janssen, Takeda, Novartis, and Amgen; a consulting/advisory role for Celgene, Janssen, Takeda, Novartis, and Amgen; and travel accommodations/expenses from Janssen, Celgene, Takeda, and Novartis. HL has received speakers bureau fees from Celgene, Janssen, Takeda, and Amgen; and research funding from Takeda and Amgen. MS, AT, BC, VH, and MSM are employees of and own stock in Celgene. CH has received honoraria from Celgene, Amgen, Bristol-Myers Squibb, Novartis, Janssen-Cilag, and Takeda.

Figures

Fig. 1

OS by frailty score using either the EQ-5D questionnaire or ECOG performance status. OS Overall Survival, ECOG Eastern Cooperative Oncology Group

Fig. 2

PFS (a) and OS (b) by frailty group. PFS Progression-free Survival, OS Overall Survival

Fig. 3

PFS (a) and OS (b) by frailty and ISS group. PFS Progression-Free Survival, OS Overall Survival, ISS International Staging System

Fig. 4

Time to treatment discontinuation (a) and first hematologic (b) and nonhematologic (c) TEAEs by frailty group. TEAE Treatment-Emergent Adverse Event

Fig. 5

PFS by treatment group in frail patients (a) and nonfrail patients (b), and OS by treatment group in frail patients (c) and nonfrail patients (d) aP values compare with MPT. PFS Progression-Free Survival, OS Overall Survival, MPT Melphalan + Prednisone + Thalidomide

Fig. 6

Comparison of Rd continuous vs MPT for PFS (a) using frailty subgroups with and without ISS stage, and comparison of Rd continuous vs MPT for OS (b) using frailty subgroups with and without ISS stage. MPT Melphalan + Prednisone + Thalidomide, PFS Progression-Free Survival, ISS International Staging System, OS Overall Survival