-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

3368 Health-Related Quality of Life (HRQoL) in Fit, Unfit and Frail Patients Enrolled in Fitness (UK-MRA Myeloma XIV): A Cross Sectional StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Research, Clinical Research, patient-reported outcomes
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Orla McCourt, PhD1*, David Allan Cairns, PhD2*, Sally Moore3*, Christopher Parrish, MBBChir, MRCP, FRCPath, MA, PhD4,5, Charlotte Pawlyn, MBBChir, PhD6,7, Frances Seymour4,8*, Ethan R Senior, MMath5*, Kara-Louise Royle5*, Jennifer Bird, MBBS, MRCP9*, Stella J. Bowcock10*, Alan Chant11*, Mark Drayson12*, Hayley Gardner13*, Matthew W. Jenner14*, John R Jones15*, Martin F. Kaiser, MD, FRCP, FRCPath16,17, Bhuvan Kishore18*, Roger Owen, MD, MRCP, FRCPath19*, Neil Rabin1*, Ruth M de Tute, MSc, PhD, FRCPath20*, Bryony Dawkins21*, David Meads, PhD21*, Sharon Gillson, BSc22*, Sharon Jackson23*, Catherine Olivier5*, Graham Jackson24* and Gordon Cook, PhD5,8*

1Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
2Leeds Institute of Clinical Trials Research, Cancer Research UK Clinical Trials Unit, Leeds, ENG, United Kingdom
3Department of Haematology, University Hospitals Bristol and Weston NHS Foundation Trust, Bristol, United Kingdom
4Leeds Teaching Hospitals NHS Trust, Leeds Cancer Centre, Leeds, United Kingdom
5Leeds Institute of Clinical Trials Research, Cancer Research UK Clinical Trials Unit, Leeds, United Kingdom
6Institute of Cancer Research, Sutton, United Kingdom
7The Royal Marsden NHS Foundation Trust, London, United Kingdom
8Leeds Myeloma Research Group and NIHR Leeds Biomedical Research Centre, Leeds, United Kingdom
9Bristol Haem/Onc Center, Bristol, GBR
10Princess Royal University Hospital, King’s College Hospital NHS Foundation Trust,, London, United Kingdom
11Patient and Public Contributor, NA, United Kingdom
12University of Birmingham, Institute of Immunology and Immunotherapy, Birmingham, United Kingdom
13Heart of England NHS trust, Birmingham, GBR
14University Hospital Southampton, Southampton, United Kingdom
15Brighton and Sussex Medical School, Brighton, United Kingdom
16The Royal Marsden Hospital NHS Foundation Trust, London, United Kingdom
17The Institute of Cancer Research, London, ENG, United Kingdom
18Heartofengland NHS FT, Birmingham, GBR
19Leeds Teaching Hospitals NHS Trust, Haematological Malignancies Diagnostics Service, Leeds, United Kingdom
20HMDS, Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
21University of Leeds, Academic Unit of Health Economics, Leeds, United Kingdom
22Leeds Institute of Clinical Trials Research, Cancer Research UK Clinical Trials Unit, Leeds, GBR
23Leeds Cancer Research UK Clinical Trials Unit, Leeds Institute of Clinical Trials Research, University of Leeds, Leeds, United Kingdom
24University of Newcastle, Department of Haematology, Newcastle, United Kingdom


In the UK in 2016-2018, more than 4 in 10 new diagnoses of multiple myeloma (MM) were in people aged at least 75 years old. Transplant-ineligible (TNE) patients are a heterogeneous group that is not well-defined by age, but by the interplay of age, physical function, cognition and comorbidity better defined as 'frailty'. There is little evidence on the effect of frailty on HRQoL in patients with MM. We examined patient-reported outcomes from participants enrolled in the FiTNEss study to understand HRQoL according to frailty group and the contribution of different elements of the International Myeloma Working Group (IMWG) frailty score (FS) to HRQoL.


FiTNEss (UK-MRA Myeloma XIV, NCT03720041) is a phase III, multi-centre, randomised controlled trial for newly diagnosed TNE MM patients. Patients receive lenalidomide, ixazomib, and dexamethasone induction and maintenance, comparing frailty score-adjusted up-front dose reductions and standard up-front dosing followed by toxicity dependent reactive dose adjustments.

Frailty was defined using the IMWG FS. It includes age (<75y, 75-80y, >80y), Katz Activity of Daily Living (ADL<=4), Lawton Instrumental Activity of Daily Living (IADL<=5), and the Charlson Comorbidity Index (CCI<=1). The UK-MRA Myeloma Risk Profile (MRP)1 was scored using age, performance status (PS), ISS and CRP.

HRQoL was measured by EORTC QLQ C30 and MY20 completed at trial entry. We used a one-way ANOVA and two-sample unequal variance t-tests to compare subscales in different frailty groups. We sought minimally important differences that were at least medium size2, and adjusted p-values using the Bonferonni correction for the 19 subscales (adjusted P = 0.05/19 = 0.0026).


Baseline HRQoL was available for 559 trial participants. Median age was 77y (<75y: 183 [32.7%], 75-80y: 248 [44.4%], >80y 128 [22.9%]), 307 (54.9%) were male and 427 (76.2%) ECOG PS0-1. 160 (28.6%) patients were classified as Fit, 182 (32.6%) were Unfit and 217 (38.8%) were Frail according to IMWG FS. 105 (18.8%) patients had CCI <=1, 60 (10.7%) had ADL<=4 and 115 (20.6%) had IADL <=5. 167 (31.0%) patients were classified as low risk, 180 (33.5%) were intermediate risk and 191 (35.5%) were high-risk according to MRP.

Contrasting IMWG fit, unfit and frail patients, significant differences were evident in 7 of 15 C30 subscales (Global Health Status [QL], Physical [PF], Role [RF], Cognitive [CF] and Emotional Functioning [EP], Appetite loss [AP], Dyspnoea [DY]) and 1 of 4 MY20 subscales (Side Effects [MYSE]) (Figure A). The largest differences in subscales were between the Fit/Unfit and Frail groups with only a single nominally different subscale (PF) between Fit and Unfit.

When comparing the frailty score elements, age group and CCI were not significantly different using C30 or MY20 subscales. However, when considering ADL: 11 of 15 C30 (QL, PF, RF. CF, Social Functioning [SF], Fatigue [FA], Pain [PA], AP, Constipation [CO], DY, Financial Problems [FP]) subscales and 2 of 4 MY20 subscales (Disease Symptoms [MYDS], MYSE) were significantly different. Similarly, when considering IADL: 10 of 15 C30 subscales (QL, PF, RF, CF, SF, FA, PA, AP, CO and DY) and 4 of 4 MY20 subscales (MYDS, MYSE, Body Image, Future Perspective Worries) were significantly different (Figure B).

When comparing between MRP risk groups, 10 of 15 C30 subscales (QL, PF, RF, CF, SF, FA, PA, AP, CO and DY) and 2 of 4 MY20 subscales (MYDS, MYSE) were significantly different. Unlike IMWG FS, 5 subscales were nominally significantly different between low and medium risk groups (QL, PF, RF, SF, DY).


The IMWG FS is associated with several domains from EORTC QLQ-C30 and MY20 at baseline with worse function and symptomatology among frail patients. Examining FS elements show that age and comorbidities do not contribute to heterogeneity in HRQoL. However, ADL and IADL are significantly associated with HRQoL. ADL elements may identify components of frailty that are potentially modifiable through supportive care and rehabilitation and could enhance HRQOL and treatment tolerability in older patients.

The MRP risk profile is associated with baseline HRQoL as shown previously and with a number of other subscales as shown here. There is evidence that the MRP can delineate subscales, including QL better than the IMWG FS.

1. Cook G, et al, The Lancet Haematology, 6(3): E154–E166.

2. Cocks K, et al, Journal of Clinical Oncology, 29(1): 89-96.

Disclosures: Cairns: Janssen: Honoraria; Celgene BMS: Honoraria, Research Funding; Amgen: Research Funding; Sanofi: Research Funding; Takeda: Research Funding. Parrish: Sanofi: Consultancy, Speakers Bureau; BMS Celgene: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Everything Genetic: Consultancy; Janssen: Speakers Bureau; Jazz: Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Gilead: Honoraria. Pawlyn: Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; BMS/Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Abbvie: Consultancy, Honoraria; Takeda: Honoraria; iTEOS: Honoraria. Seymour: Janssen: Speakers Bureau; Kite-Gilead: Speakers Bureau; Novartis: Speakers Bureau; Takeda: Honoraria. Jenner: Janssen, BMS, Pfizer, Sanofi: Consultancy, Honoraria. Jones: Takeda: Other: Support to attend conferences; Janssen: Honoraria. Kaiser: Karyopharm: Consultancy; Pfizer: Consultancy; GSK: Consultancy; Regeneron: Consultancy; Janssen: Consultancy, Honoraria; Celgene/BMS: Consultancy, Honoraria, Research Funding; Takeda: Honoraria; Seagen: Consultancy. Jackson: Oncopeptides: Consultancy; Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; J&J: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene BMS: Consultancy, Honoraria, Speakers Bureau. Cook: Janssen: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Karyopharma: Consultancy; BMS: Consultancy, Research Funding; Amgen: Consultancy.

OffLabel Disclosure: Ixazomib, in combination with lenalidomide and dexamethasone, is used as induction and maintenance treatment for transplant-ineligible newly diagnosed patients with multiple myeloma.

*signifies non-member of ASH