Impact of Comorbidities and Prospective Functional Geriatric Assessment Tools (CF-GA) As an Aide to Understand Outcome, Therapy Tolerance, Side Effects and Clinical Trial Eligibility in Multiple Myeloma (MM) Patients (pts)
Authors: Zober Alexander , Möller Mandy , Dold Sandra-Maria , Ihorst Gabriele , Hieke Stefanie , Knaus Jochen , Pantic Milena , Deschler-Baier Barbara , Knop Stefan , Einsele Hermann , Langer Christian , Muegge Lars-Olof , Poenisch Wolfram , Duyster Justus , Schumacher Martin , Waesch Ralph M. , Engelhardt Monika 
Published: October 2019

Abstract
Introduction: Cancer pts present with a highly heterogeneous health status and treatment choices are often numerous. Therefore, careful assessment of individuals' condition is highly relevant. In order to define best possible and tolerable treatment options, novel parameters and metrics for non-disease variables are needed. Albeit impairment in the Karnofsky Performance Status (KPS), Activities of Daily Living (IADL or ADL) and quality of life (QoL) are predictive for outcome in cancer and MM pts, the prognostic variables within a defined and prospectively assessed battery of established functional tests have rarely been delineated nor have their combination with disease-related risk factors or molecular markers been meticulously assessed. Their prognostic value for functional decline and overall survival (OS) has also not been tested and validated prospectively.
Methods: We performed this comorbidity and functional geriatric assessment (CF-GA) in consecutive MM pts treated at our center according to our institutional Comprehensive Cancer Center pathway. The GA was prospectively obtained prior to initiation of anti-myeloma treatment and reflected pts' baseline health status rather than being confounded by toxicities induced by therapy. This CF-GA included the IADL, ADL, Timed Up and Go-Test, malnutrition, pain, rating of fitness, SF12-QoL and geriatric depression scale. Moreover, established comorbidity (CM) scores: ß2MG/eGFR (Eur J Haematol. 2009;83:519-27), Kaplan Feinstein (KF), Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), Charlson Comorbidity Index (CCI) and initial Freiburg Comorbidity Index (iFCI) vs. revised FCI (rFCI) were assessed. This CF-GA was performed as one screening tool to assess pt fitness as well as to predict survival and toxicities in elderly myeloma pts. Results: Characteristics of 131 pts, currently included in this CF-GA, were typical for tertiary centers with a median age of 63 years (40-83), all with symptomatic disease. Their median hemoglobin was 10.8g/dl (7.6-14.7), the eGFR 68ml/min/1.73qm (7-136), the ß2-MG 4.4mg/l (0.8-38.4) and BM infiltration 40% (3-90). The baseline frailty assessment revealed a median KPS of 80% (40-100). The fitness score scaled both by physicians and patients was 4 vs. 3 (1-6), demonstrating that physicians overestimate pts' performance status and objective tests to verify this are essential. Median functional results for the IADL were 5 (1-8), for the ADL 4 (2-6), for pain 2 (0-10), for malnutrition 4 (0-14) and for cognitive deficiency via Mini Mental State Examination 28 (16-30). The median geriatric depression scale was 3 (0-13) and Timed Up and Go-Test 10 (4-30). Median CM scores were substantially different with an iFCI of 0 (0-3), ß2MG/eGFR of 1 (0-2), KF of 1 (0-3), HCT-CI of 2 (0-8), rFCI of 4 (0-9) and CCI of 7 (0-12). Highly valuable CF-GA-tools seem currently the IADL, Timed Up and Go-Test and rFCI. Since CF-GA is a time and man-power consuming procedure, we have presently completed a web account that allows the straightforward assessment of the rFCI for MM pts (https://rfci-score.org). This permits to perform this score in only 1-2 minutes. Moreover, we continue to perform this prospective assessment in more MM pts at our center and within a multicentre approach within the German Study Group Multiple Myeloma(DSMM) and will thereby also assess whether these function deficits and tests change over time. Prior scores to define fit, intermediate and frail pts (Blood. 2015;125:2068-74) will be compared with our risk group definitions and their predictive power for progression free survival, overall survival, side effects, therapy termination/discontinuation and early mortality will be evaluated. Adverse risk groups will allow to test and validate the most significant predictors of survival outcomes.
Conclusions: Our CF-GA and rFCI contain easily assessable and reliable tests, which are of value to further test for their discriminative character in MM pts. Moreover, most predictive CF-CA tools need to be determined in prospective multicentre cohorts and need to be included in future clinical trials. We advocate our CF-GA and rFCI to foresee treatment toxicity, facilitate treatment decisions and guide personalized therapies. Timely identification and management of risk factors in MM pts are important considerations in the daily care of older and frail cancer pts, specifically those with MM.

Disclosures
Zober: Deutsche Krebshilfe: Other: grant. Knop:Celgene Corporation: Consultancy. Einsele:Amgen/Onyx: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Research Funding, Speakers Bureau. Engelhardt:Deutsch Krebshilfe: Other: grant.