Frailty in relapsed/ refractory multiple myeloma registration trials.

Abstract

e20017 Background: Multiple Myeloma (MM) is predominantly a disease of older adults with a median age of onset at 70 years. There is growing interest in using criterion other than chronological age, like frailty, to determine fitness for treatment and ultimately improve clinical outcomes in MM. Frailty is the accumulation of aging-associated diseases and disabilities, making patients more vulnerable to adverse outcomes when exposed to stressors like anti-cancer treatment. MM frailty measures have primarily been developed and tested in newly diagnosed patients. MM patients typically relapse, but there is limited knowledge regarding the prevalence of frailty in the relapsed/refractory (RRMM) setting. The aim of this research was to determine the prevalence of frailty in RRMM commercial clinical trials, at the time of trial enrollment, using the International Myeloma Working Group (IMWG) Frailty Index. Methods: We pooled baseline data from 6 RRMM clinical trials submitted for FDA regulatory review between 2010 and 2020. The IMWG Frailty Index was calculated for each patient based on 4 variables: age (≤75, 75–80, >80 years, score 0, 1, 2, respectively), Charlson Comorbidity Index (CCI; ≤1 or ≥2, score 0 or 1), and (Instrumental) Activities Daily Living (ADL >4 or ≤4, score 0 or 1; IADL >5 or ≤5, score 0 or 1). As ADLs and IADLs are not routinely collected in clinical trials, we substituted this information with corresponding EQ-5D items on self-care and usual activities. Fit, Intermediate-fit, and Frail patients received IMWG scores of 0, 1, and ≥2 respectively. Descriptive statistics for frailty were summarized by age. Results: 2766 RRMM patients were aggregated from six clinical trials. 1502 (54%) patients were Fit, 780 (28%) were Intermediate-fit, and 484 (18%) were Frail. The median age of patients across trials was 65 [range 30-91]. The median CCI was 0 [range 0-7] out of 37. IMWG frailty scores have been presented by age category in Table. Prevalence of frailty at baseline by age in RRMM registration trials. Conclusions: Most patients in RRMM registration trials were classified as Fit at baseline, using the IMWG Frailty Index. This was expected due to stringent trial enrollment criteria which exclude patients with severe comorbidities, as reflected in the low average CCI. The IMWG index heavily weights patient age. As such, there were no Fit patients in the 75 – 80 year old cohort and only Frail patients in the 80+ year old cohort. This is despite the fact that these older patients met stringent trial enrollment criteria and had CCI scores < 7. Chronologic age alone should not be used as an absolute exclusion for treatment, whether in the trial or real-world setting. Future research into frailty indices that do not heavily weight age is warranted.[Table: see text]