P-116: The simplified frailty index (S-FI) identifies a less vulnerable population of frail patients than patients who are defined frail using the International Myeloma working Group Frailty index (IMWG-FI)

Introduction: The International Myeloma working Group introduced a frailty index (IMWG-FI), which classifies patients as either fit, intermediate-fit or frail, based on age, comorbidities and dependency in (instrumental) activities of daily living ((I)ADL). A simplified frailty index (S-FI) has been introduced, replacing (I)ADL by the WHO performance score (WHO-PS). Even though both scores predict outcome, it is currently unknown whether the level of frailty is identical between the 2 scores.

Methods: This is a pooled analysis of the HOVON 123 and HOVON 143 studies. In the HOVON 123 study, 238 non-transplant eligible newly diagnosed multiple myeloma patients, were treated with 9 cycles of melphalan, prednisone and bortezomib. In the HOVON 143 study, 65 frail and 65 intermediate fit NTE-NDMM patients, according to the IMWG-FI, were treated with 9 cycles of ixazomib, daratumumab and low dose dexamethasone (Ixa-Dara-dex), followed by maintenance until progression with a maximum of 2 years. Patients with unknown frailty score, either according to the IMWG-FI or S-FI, were excluded from analysis. Patients were classified as fit, intermediate fit and frail, using both indexes to determine the concordance rates and to investigate patient characteristics and clinical outcome of the different frailty groups.

Results: The IMWG-FI and S-FI were missing in 19 patients. As fit patients were underrepresented (n=8) we excluded this subgroup, leaving 341 patients. Of the 67 patients who were intermediate-fit according to the S-FI, 61 patients (91%) remained intermediate-fit and 6 (9%) patients were reclassified to frail when using the IMWG-FI. Of the 272 patients who were frail based on the S-FI, 202 patients (74%) remained frail, however, 70 patients (26%) were reclassified to intermediate-fit when using the IMWG-FI.
These 70 frail patients who would be classified as intermediate-fit when using the IMWG-FI had favorable patient- and disease characteristics, compared to the 202 patients who were frail according to both scores. They were younger (>80 years: 0% versus 56%), more often ADL independent (100% vs 69%) and IADL independent (93% vs 40%), had less comorbidities (CCI ≤1: 80% vs 49%) and a more favorable ISS stage (ISS 3: 27% vs 48%). In addition, PFS2 and OS were significantly longer in these 70 reclassified patients (median PFS2 40.0 versus 29.1m, HR 0.66 (95% CI: 0.47-0.91), p=0.01 and median OS 50.6m versus 24.1m, HR 0.55 (95% CI: 0.39-0.80), p=0.0014), as compared to the 202 patients who were frail based on both scores.

Conclusions: We here show that the S-FI identifies more patients as frail, including patients that would have been classified as intermediate fit when the gold standard, the IMWG-FI, was used. These reclassified frail patients have favorable patient- and disease characteristics, translating in a superior PFS2 and OS as compared to the subgroup of frail patients who were defined frail in both classifications. This hampers comparisons between studies using the S-FI versus the IMWG-FI.