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2280 Isatuximab with Pomalidomide and Dexamethasone Provides Comparable Efficacy Outcomes in Frail Routine Care Myeloma Patients in a UK-Wide Cohort

Program: Oral and Poster Abstracts
Session: 905. Outcomes Research—Lymphoid Malignancies: Poster I
Hematology Disease Topics & Pathways:
Biological therapies, Antibody Therapy, Clinical Practice (Health Services and Quality), Plasma Cell Disorders, Combination therapy, Diseases, Therapies, Lymphoid Malignancies
Saturday, December 10, 2022, 5:30 PM-7:30 PM

Faouzi Djebbari1*, Alexandros Rampotas1*, Grant Vallance1*, Fotios Panitsas2*, Nanda Basker3*, Gina Sangha4*, Beena Salhan5*, Farheen Karim6*, Firas Al-Kaisi, MD7*, Amy Gudger8*, Loretta Ngu9*, Matt Poynton10*, Ho Pui Jeff Lam11*, Lowri Morgan12*, Laura Yang13*, Jennifer Young14*, Mairi Walker15*, Ismini Tsagkaraki16*, Laura Anderson17*, Saleena Rani Chauhan18*, Rebecca Maddams19*, Richard Soutar20*, Margarita Triantafillou21*, Steve Prideaux22*, Abubaker Obeidalla23*, Ceri Bygrave24*, Supratik Basu25* and Karthik Ramasamy26

1Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom
2Department of Haematology and Bone Marrow Transplantation, National and Kapodistrian University of Athens, Laikon General Hospital, Athens, Greece
3University Hospital Southampton, Southampton, United Kingdom
4Milton Keynes Hospital, Milton Keynes, United Kingdom
5Birmingham Heartlands Hospital, Birmingham, ENG, United Kingdom
6The Royal Wolverhampton NHS Turst, Wolverhampton, United Kingdom
7Royal Derby Hospital, Derby, ENG, United Kingdom
8Queen Elizabeth Hospital, Birmingham, United Kingdom
9Royal Devon & Exeter NHS Foundation Trust, Exeter, United Kingdom
10Royal Berkshire Hospital, Reading, United Kingdom
11Guy's and St Thomas NHS Foundation Trust, London, ENG, United Kingdom
12University Hospital of Wales, Cardiff, United Kingdom
13University Hospitals Sussex NHS Foundation Trust, Worthing, United Kingdom
14Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle, United Kingdom
15University Hospital Crosshouse, Crosshouse, United Kingdom
16Stoke Mandeville Hospital, Aylesbury, United Kingdom
17Royal United Hospital Bath, Bath, GBR
18Worcestershire Acute Hospitals NHS Trust, Worcester, United Kingdom
19Poole Hospital, Poole, United Kingdom
20Beatson Oncology Centre, Glasgow, United Kingdom
21Manchester Royal Infirmary, Manchester, United Kingdom
22Great Western Hospital, Swindon, United Kingdom
23Wexham Park Hospital, Slough, United Kingdom
24Department of Haematology, University Hospital of Wales, Cardiff, United Kingdom
25The Royal Wolverhampton NHS Trust and University, West Midlands Research Consortium (WMRC), Wolverhampton, United Kingdom
26Department of Clinical Haematology, Oxford University Hospitals NHS Foundation Trust, Oxford, United Kingdom

Background: The use of frailty assessments in the management of relapsed/refractory multiple myeloma (RRMM) patients is required, in order to individualise treatment decisions, which would aim to reduce the risk of under-treating fit patients or over-treating frail patients. In addition to IMWG, R-MCI and MRP myeloma prognostic frailty tools, a new simplified frailty score developed by Facon et al (2020) was predictive of outcomes in elderly newly diagnosed myeloma patients treated as part of the FIRST trial. However, there are no data to describe its utility in RRMM patients treated in the real-world. Method: We conducted a UK-wide retrospective real-world study of RRMM patients treated with isatuximab plus pomalidomide and dexamethasone (IsaPomDex). We report patient characteristics, and clinical outcomes according to frailty categories using the new frailty scoring system, including overall response rate (ORR), progression-free survival (PFS), duration of response (DOR), overall survival (OS) and adverse events (AE). Frailty scoring was based on 3 key components: age (≤75 years: 0, 76–80 years: 1, >80 years: 2), Charlson co-morbidity index (CCI) score (≤1:0, >1: 1) and ECOG performance status (PS) (0: 0, 1:1, ≥2:2). The sum of all 3 components would define patients as frail (if ≥2) or intermediate-fit (if <2). Results: In a total cohort of 106 patients evaluable for frailty, median follow-up (FU) was 12.1 months (IQR 10.1-18.6 months). Seventy-two patients (67.9%) were frail, whilst 34 patients (32.1%) had an intermediate-fit status (i.e. non-frail). Patients in the frail subgroup had a higher median age (frail: 71 vs. intermediate-fit: 57.5 years), a higher proportion of patients with PS score of ≥1 (frail: 95.9% vs. intermediate-fit: 29.4%), a higher co-morbidity burden expressed as a higher median CCI score (frail: 4 vs. intermediate-fit: 1), and poor renal function defined as GFR<60ml/min (frail: 51.4% vs. intermediate-fit: 26.5%). Median number of prior therapies was identical between subgroups (3 vs. 3). Patients in the frail subgroup received a numerically lower median number of IsaPomDex cycles during follow-up, but without a statistical significance (frail: 6 vs. intermediate-fit: 9.5, p=0.1664). There was no statistical difference in treatment discontinuation rates (frail: 51.4% vs. intermediate-fit: 50%, p=0.894). Discontinuation rate due to death was numerically higher in the frail subgroup but without statistical significance (frail:16.7% vs. intermedicate-fit:11.8%, p=0.234). ORR was comparable across frailty subgroups (frail: 65.3% vs. intermediate-fit: 67.7%, p=0.779). Median PFS was numerically higher in the non-frail group but without statistical difference (frail: 10.1 vs. intermediate-fit: 13.7 months, log-rank p=0.5259). There was no statistical difference in median DOR (frail: 10.1 vs. intermediate-fit: 10.2 months, p=0.685). There was a trend for a longer median OS in the non-frail group but without statistical difference (frail: 15 months, 95% CI 12-NE vs. intermediate-fit: not reached, 95% CI 16.7-NE, log-rank p=0.3571). Data on AEs is presented after a median number of IsaPomDex cycles (IQR) of 4 (2-8), and a median follow up (IQR) of 3.7 months (0.5-12.4). Incidence rate of any grade AEs was (frail:87.5% vs. non-frail: 88.4%, p=0.763). Incidence rate of any grade haematological AEs was (frail: 76.4% vs. non-frail: 67.6%, p=0.341). Incidence rate of ≥G3 infections was (frail: 22.2% vs. non-frail: 11.8%, p=0.199). Incidence rate of ≥G3 haematological AEs was (frail: 58.3% vs. non-frail 38.2%, p=0.053). Incidence rate of AE-related inpatient hospitalisations was (frail: 26.4% vs. non-frail: 14.7%, p=0.18). Our study is limited by its retrospective, non-randomised nature with the inherent possibility of unmeasured confounding factors, patient selection bias, the potential for medical chart misinterpretation, and under-reporting of toxicities. Conclusion: Despite the limitations of our study, we showed the high prevalence of frailty in RRMM patients in the real-world (67.9%), which is significantly higher than in the overall ICARIA-MM trial population (28%) (Schjesvold et al 2021). Our study also demonstrated comparable efficacy outcomes between frailty subgroups (ORR/PFS/DOR), but a trend for worse toxicity outcomes in frail compared to intermediate-fit patients.

Disclosures: Djebbari: Sanofi: Honoraria; BMS: Honoraria. Basu: Sanofi, Pfizer, BMS: Consultancy, Speakers Bureau; Sanofi: Honoraria, Other: advisory board. Ramasamy: Takeda, Bristol Myers Squibb, Janssen, Amgen, GlaxoSmithKline: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Research Funding, Speakers Bureau; Sanofi, Adaptive biotech, Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau.

*signifies non-member of ASH