Introduction: Multiple Myeloma (MM) primarily affects elderly patients (approximately 30%, aged ≥75 years), with heterogeneity which is largely attributable to frailty. Frailty is a multidimensional syndrome characterized by decreased physiological reserve, functional abilities, comorbidities, polypharmacy, nutritional status, and cognitive impairment, with increased susceptibility to develop adverse events. The International Myeloma Working Group Frailty Index (IMWG-FI) is a widely used tool for assessing frailty. Limited studies have been conducted in the real world using Comprehensive Geriatric Assessments (CGA). This study aimed to identify frail MM patients at diagnosis based on CGA by geriatricians and evaluate its impact on outcomes.

Methods: This retrospective observational study included newly diagnosed multiple myeloma (NDMM), evaluated at a single Spanish institution between January 2017 and May 2024. All patients had symptomatic MM with the age ≥ 68 years old. At diagnosis, CGA was performed by a geriatrician, classifying patients into 4 groups based on frailty and functional reserve. (Balducci L. Eur J Cancer. 2000; 36 (14): 1741-1754. BJU Int. 2010; 106 (4): 462-469.132). Overall survival (OS) was estimated using the Kaplan-Meier method, and the groups were compared using the Log-rank test. P values <0.05 were considered statistically significant.

Results: A total of 75 patients were included with a median age of 80 years (range 68.7-93.6), 80% aged ≥ 75, and 57% over 80 years old. Females were 50.7%. Thirty percent of patients had ECOG performance status ≥ 2. High-risk cytogenetics were identified in 26/60 (43%). International Staging System (ISS)-3 was found in 18/67 (27%). Bone fracture was observed in 32 (43.8%). The median time from MM diagnosis to CGA was 18 days (IQR 7.0-34). Based on GCA, we found ADL >4 in 62/73 (85%) and IDAL >5 in 30/64 (46%) of patients. Abbreviated Charlson Comorbidity Index (ACCI) of ≥ 2 was seen in 30/72 (41.7 %).According to CGA, 14 (19%) patients were classified as robust (type I), 34 (46%) as pre-frail (type II) with potentially reversible impairments, 23 (31%) as frail (type III) with a low functional reserve, and 2 (4%) for supportive care (type IV). Among patients with an ECOG < 2, 33 (70%) were classified as type I-II (Fit or pre-frail), and 14 (30%) were frail due to the CGA. According to the IMWG-FI, patients were classified as fit in 10/73 (13.6%), intermediate in 16/73 (22%), and frail in 47/73 (64.3%). Modified VRD was the most commonly used first-line therapy (22.2%), followed by RD (20.8%) and DRD (12.5%).) Treatment adjustments due to frailty were applied to 45 (62.5%) patients, while adjustments due to comorbidities were done in only 13 (19.1%). According to IMWG-FI, 47/73 (64.3%) of the study population were frail. Among these frail patients, half, 24/47(51%), were classified as types I-II (fit/pre-frail) based on CGA. There was no significant agreement between the IMWG-FI criteria and Geriatric Assessments, as evidenced by the Kappa statistic of 0.30 with (95% Confidence Interval (CI), 0.15-0.45). The incidence of frailty was 64.3% based on IMWG-FI and 35% according to CGA (Types III-IV) (P < 0.001). The median follow-up was 30 months (Interquartile range (IQR), 12-59.6). The study revealed a significant difference in overall survival between patients with CGA types I-II and those with GA types III-IV, with a hazard ratio (HR) of 2.66, favoring OS for type I-II (95% CI: 1.12- 6.34, P < 0.001). Grade ≥ 3 hematologic toxicities were observed in 22%, non-hematologic in 50% (half due to infections), and treatment discontinuation occurred in 37.6%.

Conclusions: Managing MM in elderly patients requires a comprehensive approach. Although several scoring systems have been proposed to identify frailty, none have been widely incorporated into clinical practice. In this study, we observed a high prevalence of frailty according to IMWG-FI, primarily due to the older age of our cohort. One of the key findings was that half of the patients classified as frail by IMWG-FI were fit or pre-frail by CGA. Among patients with ECOG 0-1, 30% were frail based on CGA. Our analysis also highlighted the Impact of CGA on overall survival (OS). Integrating CGA into the treatment strategy for elderly patients with newly diagnosed MM enables more precise frailty assessment, leading to improved treatment outcomes.

Disclosures

No relevant conflicts of interest to declare.

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2024
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