Utilizing a two-step frailty assessment strategy in older adults with multiple myeloma (MM): A decision curve analysis.
Authors: Gahagan Andrew , Pasala Monica Sai , Ubersax Clare , Tucker Abigail , Harmon Christian , Bal Susan , Godby Kelly Nicole , Ravi Gayathri , Costa Luciano J. , Williams Grant Richard , Giri Smith 
Published: June 2023

8061 Background: The International Myeloma Working Group Frailty Index (IMWG-FI) has been shown to predict risk of toxicity and mortality in older adults with MM (Palumbo et al., Blood 2015). However, IMWG-FI requires a geriatric assessment (GA) that is not routinely done in clinical practice due to time constraints. A simplified frailty index (SFI; Facon et al., Leukemia 2020) has been proposed as an alternative using ECOG PS as a proxy to functional status. We previously reported a moderate concordance between these two frailty indices (Kappa statistic 0.50; Gahagan et al., ASH 2022). Here, we examined if SFI can be utilized as a screening tool to identify patients who would benefit from a formal GA and frailty assessment. We hypothesized that a two-step approach would minimize the need for unnecessary GAs, while saving time in clinical practice. Methods: For this analysis, we included patients ≥50yo with newly diagnosed (ND) or Relapsed/Refractory (RR)-MM at a single institution initiating a new treatment regimen (1st to 6th line) who are enrolled in a prospective registry (NCT05556928). All patients underwent a GA prior to a new line of therapy. ECOG PS and comorbidities were abstracted from medical records. We calculated IMWG-FI and SFI using published methods. Sensitivity, specificity along with their 95% CI were calculated for both SFI and IMWG-FI, using published SFI cutpoints. Lastly, we used decision curve analysis (DCA) as described by Vickers et al. to calculate the benefit of frailty screening using SFI for detection of non-frail patients and avoiding unnecessary GAs. We assumed that reasonable threshold probabilities were 0.25 and 0.33 respectively indicating that missing an unfit patient was 3 and 2 times worse than exposing a fit patient to an unnecessary GA (odds of 1:3 and 1:2 respectively). We quantified the net benefit (NB) of this two-step frailty assessment versus GA-for-all in terms of net reduction in unnecessary GAs. Results: A total of 146 adults with MM (49 ND-MM, 51 pre-transplant, and 46 RR-MM) starting a new line of therapy between 8/2020-1/2022 were included in this study. The median age was 62 (IQR 57-70) with 53% males and 36% blacks. The distribution by IWMG-FI was 43% fit, 32% intermediate-fit, and 25% frail. Using SFI, 32% of patients were frail. Using a cutpoint of ≥2, SFI as a screening tool had a sensitivity of 89.2% (95% CI 75-96%) and a specificity of 65% (95% CI 56% to 73%). DCA showed that selecting candidates for GA based on a two-step strategy (SFI followed by IMWG-FI) led to an absolute 40-45% reduction in the number of unnecessary GAs without missing any frail patients. Conclusions: Our results suggest that using a two-step frailty assessment strategy of SFI as a screening tool followed by confirmation with IMWG-FI reduces the need for unnecessary GAs by 40-45% and may be more suitable for integration in busy oncology practice.