-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.

4748 Dynamic Frailty Assessment in Transplant Non-Eligible Newly Diagnosed Myeloma Patients: Initial Data from UK Myeloma Research Alliance (UK-MRA) Myeloma XIV (FiTNEss): A Frailty-Adjusted Therapy StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Acquired Marrow Failure Syndromes, clinical trials, Research, elderly, Bone Marrow Failure Syndromes, Combination therapy, Clinical Research, Diseases, Therapies, Study Population, Human, Minimal Residual Disease
Monday, December 11, 2023, 6:00 PM-8:00 PM

Gordon Cook, PhD1,2*, Charlotte Pawlyn, MBBChir, PhD3, Kara-Louise Royle1*, Ethan R Senior, MMath1*, Dax Everritt1*, Jenny Bird4*, Stella J. Bowcock5*, Bryony Dawkins6*, Mark Drayson7*, Sharon Gillson, BSc8*, Catherine Olivier1*, Alan Chant9*, Matthew W. Jenner10*, John Robert Jones, MD11*, Martin F. Kaiser, MD, FRCP, FRCPath12, Bhuvan Kishore13*, David Meads, PhD6*, Neil Rabin14*, Roger Owen, MD, MRCP, FRCPath15*, Ruth M de Tute, MSc, PhD, FRCPath16*, Christopher Parrish, MBBChir, MRCP, FRCPath, MA, PhD1,17, David Allan Cairns, PhD18* and Graham Jackson19*

1Leeds Institute of Clinical Trials Research, Cancer Research UK Clinical Trials Unit, Leeds, United Kingdom
2Leeds Myeloma Research Group and NIHR Leeds Biomedical Research Centre, Leeds, United Kingdom
3Institute of Cancer Research, Sutton, United Kingdom
4Department of Haematology, University Hospitals Bristol NHS Foundation Trust, Cambridge, GBR
5Princess Royal University Hospital, King’s College Hospital NHS Foundation Trust,, London, United Kingdom
6University of Leeds, Academic Unit of Health Economics, Leeds, United Kingdom
7University of Birmingham, Institute of Immunology and Immunotherapy, Birmingham, United Kingdom
8Leeds Institute of Clinical Trials Research, Cancer Research UK Clinical Trials Unit, Leeds, GBR
9Patient and Public Contributor, NA, United Kingdom
10University Hospital Southampton, Southampton, United Kingdom
11East Sussex Healthcare NHS Trust, London, United Kingdom
12The Institute of Cancer Research, London, ENG, United Kingdom
13Heartofengland NHS FT, Birmingham, GBR
14Department of Haematology, University College London Hospitals NHS Foundation Trust, London, United Kingdom
15Leeds Teaching Hospitals NHS Trust, Haematological Malignancies Diagnostics Service, Leeds, United Kingdom
16HMDS, Leeds Cancer Centre, Leeds Teaching Hospitals NHS Trust, Leeds, United Kingdom
17Leeds Teaching Hospitals NHS Trust, Leeds Cancer Centre, Leeds, United Kingdom
18Leeds Institute of Clinical Trials Research, Cancer Research UK Clinical Trials Unit, Leeds, ENG, United Kingdom
19University of Newcastle, Department of Haematology, Newcastle, United Kingdom


Multiple myeloma (MM) is a blood cancer that predominates in the older adult with significant morbidity and mortality. Frailty is increasingly recognized as a predictor for long- and short-term outcomes, with those who are frailer at risk of greater toxicity, treatment discontinuation and poorer survival. Identifying and tailoring treatment for frail older patients with MM remains an unmet need. The International Myeloma Working Group frailty score (IMWG FS) is a prognostic biomarker for survival, but no evidence exists for its predictive biomarker potential. In addition, defining frailty at a single timepoint (baseline) by the IMWG FS may mask disease overlay and the improvements seen with therapy delivery. Understanding both improvements and deteriorations in frailty during treatment may have important implications for dynamic treatment delivery.

Study Design and Methods

The UKMRA Myeloma XIV FiTNEss trial (NCT03720041) is a phase III, multi-centre, randomised controlled trial for newly diagnosed patients with MM ineligible for a stem cell transplant. The primary objectives of the study are 1) to compare early treatment cessation (within 60 days of randomisation) between patients randomised to standard (reactive) and frailty-adjusted (adaptive, based on IMWG FS) induction therapy delivery with the triplet ixazomib, lenalidomide and dexamethasone (IRd) and 2) to compare progression-free survival for maintenance lenalidomide (R) and lenalidomide plus ixazomib (IR). Baseline revised IMWG FS (considering only those scoring >=3 frail) and UKMRA Myeloma Risk Profile (MRP) were determined. Here we report the changes in IMWG FS for the patients recruited to the standard (toxicity-reactive) arm, including demographic data and the identification of an ultra-frail group.


The FiTNEss trial opened on 04/08/2020 and at the time of data cut off (01/06/2023) recruitment is active at 84 sites, with 638 patients randomised. Baseline characteristics for the randomised patients are shown in Table 1. The median age of patients is 76 years (range 62, 93) with 34.8% aged 76-80 and 22.3% over 80. The IMWG FS at baseline for the full trial cohort was FIT 182/638 (28.5%), UNFIT 207/638 (32.4%) and FRAIL 249/638 (39.0%). Revised IMWG FS at baseline was Fit 28.5%, Unfit 56.0% and Frail 15.5% with MRP non-high risk (Fit or Unfit, nHR) in 64.3% and MRP HR (Frail) in 35.7% in patients with data available.

For descriptive analysis of FS dynamism, we assessed the impact on FS of delivery of IRD in the control arm (n=319), calculating the FS at 2, 4, 6 and 12 months. The majority of changes were seen at 2 months across the frailty categories. For Fit patients, 20.9% demonstrated a deterioration in FS score at any timepoint. For Unfit patients, 26.7% demonstrated a deterioration in FS score whilst 16.2% demonstrated an improvement in FS at any timepoint. For Frail patients, 15.4% demonstrated an improvement in FS at any timepoint (Figure 1). Of those who demonstrated a deterioration in FS, 59.1% experienced a treatment related safety event. In those who demonstrated an improvement in FS, 26.3% experienced a treatment related safety event. Of the 250 whose FS remained constant 34% experienced a treatment related safety event.

For frail patients, 119 could be stratified further and 57% were classified as Ultra-Frail (IMWG FS Frail and MRP HR).


The FiTNEss trial demonstrates the feasibility of recruiting older, less fit patients to clinical trials. The IMWG FS does demonstrate a dynamic biomarker potential both representing improved functionality in relation to disease response to therapy, as well as deterioration consequential to treatment-emergent toxicity. In addition, the concept of ultra-frail represents an exciting possibility to further stratify patients who may need additional support in order to improve their outcomes. Further work in these two areas is on-going as the trial dataset matures.

Disclosures: Cook: Amgen: Consultancy; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Sanofi: Consultancy; Karyopharma: Consultancy. Pawlyn: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: 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; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria; iTEOS: Honoraria. Jenner: Janssen, BMS, Pfizer, Sanofi: Consultancy, Honoraria. Kaiser: Seagen: Consultancy; Karyopharm: Consultancy; Takeda: Honoraria; Celgene/BMS: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Regeneron: Consultancy; GSK: Consultancy; Pfizer: Consultancy. Parrish: BMS Celgene: Consultancy, Speakers Bureau; Sanofi: 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. Cairns: Sanofi: Research Funding; Celgene BMS: Honoraria, Research Funding; Janssen: Honoraria; Amgen: Research Funding; Takeda: Research Funding. Jackson: Sanofi: Consultancy, Honoraria, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria; Oncopeptides: Consultancy; Takeda: Consultancy, Honoraria, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau; J&J: Consultancy, Honoraria, Research Funding; Celgene BMS: Consultancy, Honoraria, Speakers Bureau.

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

*signifies non-member of ASH