Cognitive Impairment, Hypoalbuminemia, High CRP Level and Past History of Gastro-Intestinal Ulcer: 4 Markers of Frailty Which Identify Older Patients with Malignant Hemopathies Who Shouldn't Benefit from Chemotherapy
Authors: Dubruille Stephanie , Kenis Cindy , Thibaud Vincent , Libert Yves , Delforge Michel , Dal Lago Lissandra , Roos Myriam , Borghgraef Cindy , Thierry Pepersack , Wildiers Hans , Bron Dominique 
Published: October 2019

Abstract
INTRODUCTION: Major progresses have been achieved to identify older patients with malignant hemopathies who should be treated with standard doses of chemotherapy. However, a reliable frailty score remains urgently needed to better define the unsuspected vulnerable population that does not benefit from chemotherapy. In the literature, three clinical (functional decline, cognitive impairment (CI) and comorbidities) and two biological (low albumin level and high IL-6 level) factors are frequently associated with a poor overall survival (OS) and/or chemotherapy-related toxicities.
OBJECTIVE: To investigate the reliability of a simple clinico-biological tool for the screening of frail patients with malignant hemopathies to predict a poor survival (<6 months).
METHODS: 285 consecutive patients (65-90yrs) with malignant hemopathies admitted to receive chemotherapy where included in a prospective multicentric study conducted in the Inst. J. Bordet (ULB, Brussels) and in the University Hospitals Leuven (KU, Leuven). A Comprehensive Geriatric Assessment (CGA) was performed. Univariate and multivariate Cox proportional hazards models were used to evaluate the value of functional decline, abnormal cognitive function, comorbidities, low albumin and CRP level to predict 1-year survival.
RESULTS: One hundred and ninety-two patients were evaluable for the clinico-biological screening tool (NHL, n=111; CLL, n=19; MM, n=29; AML, n=20; ALL, n=3; LMMC, n=7; MDS, n=3). Eighty-three percent were considered to have a more favorable prognosis (NHL, CLL or MM). Functional decline was associated with abnormal cognitive function (P=0.029) and inflammation (P=0.002). Based on our previous analyses in the Charlson Comorbidity Index we took the strongest prognostic factor: gastro-intestinal (GI) ulcer (P=0.001). A "frailty" scoring system was thus developed, based on our 4 independent predictive factors for poor survival: CI (MMSE<27, n=57), presence of GI ulcer (n=29), low albumin level (alb<3.5g/dl, n=57) and surrogate marker of IL-6 level (CRP≥2mg/l, n=146). The population was stratified into 3 groups: "fit" (score=0-1, n=102), "vulnerable" (score=2, n=58) and "frail" (score=3-4, n=32). The one-year survival was 80% in "fit" and 53% in "vulnerable" patients (HR=2.75; 95% CI=1.54-4.91; P=.001). In "frail" patients 38% were alive at one-year (HR=4.87; 95% CI=2.61-9.09; P<.001) with a median survival of 5 months. Causes of death remain disease-related in a majority of the patients (69%).
CONCLUSIONS: In our selected population of "clinically fit patients" referred to receive chemotherapy for malignant hemopathies, our frailty score helps the clinician to predict a very poor outcome. This frailty score detects unsuspected frailty in patients who may benefit from palliative care. Ongoing prospective analyses in a larger cohort of malignant hemopathies will be updated to validate the reliability of this score.

Disclosures
Delforge: Amgen, Celgene, Janssen and Takeda: Consultancy; Celgene and Janssen: Research Funding.