Electronic FRAIL score may predict treatment outcomes in older adults with myeloma.

INTRODUCTION: Frailty is a known risk factor for older patients with myeloma. Here we present realworld data using a computer-generated frailty assessment score (FRAIL score), based on 5 clinically derived parameters, in predicting patient outcomes. METHODS: Older patients with newly diagnosed multiple myeloma who received frontline treatment with cyclophosphamide-bortezomib-dexamethasone had their FRAIL score retrospectively assessed. Treatment outcomes were assessed using standard IMWG criteria, and event free survival and overall survival determined. RESULTS: 155 patients were analysed. Compared to those who were assessed as non-frail (FRAIL score 0-1) likely-frail patients (score ≥ 2) were less likely to complete the full course of treatment (24.3% vs 53.4%, p = 0.002), and more likely to terminate treatment due to toxicities (35.1% vs 22.0%, p = 0.109), as well as having a greater number of patients stop treatment early for reasons other than toxicity or progression (27.0% vs 10.2%, p = 0.010). After a median follow up of 42.5 months, likely-frail patients were found to have a trend for shorter event-free survival (median EFS, 8.7 vs 17.9 months, p = 0.064) and statistically inferior overall survival (median OS, 30.2 vs 49.8 months, p < 0.001). After adjusting for age, stage, and Charlson comorbidity index, FRAIL score was prognostic for OS (HR = 3.47, 95% CI 1.88-6.4), but not EFS (HR = 1.28, 95%CI 0.79-2.06). CONCLUSION: The FRAIL score is independently predictive of overall survival in older patients with myeloma receiving bortezomib-based induction chemotherapy and can help identify those patients more likely to experience treatment toxicity.

Upfront lower dose lenalidomide is less toxic and does not compromise efficacy for vulnerable patients with relapsed refractory multiple myeloma: final analysis of the phase II RevLite study.

The combination of lenalidomide and dexamethasone is an established treatment for patients with multiple myeloma (MM). Increasingly, treatment attenuation is advocated for frail/elderly patients to minimize toxicity even though there have been no prospective studies to demonstrate whether lenalidomide dose attenuation impacts on response and survival outcome. This prospective multicentre phase II study assessed the efficacy and tolerability of lower dose lenalidomide (15 mg) and dexamethasone (20 mg) in 149 eligible patients with relapsed/refractory MM aged over 59 years and/or with renal impairment. The overall response rate was 71% (complete response 15%). Median (range) progression-free survival (PFS) and overall survival (OS) were 8·9 (6·9-11·5) and 30·5 (20·0-36·2) months, respectively. Upon formal statistical comparison of these endpoints to that of a matched cohort of patients from the pivotal phase III MM009/MM010 studies who received standard-dose lenalidomide (25 mg) and high-dose dexamethasone (40 mg) no difference was seen in PFS (P = 0·34) and OS (P = 0·21). Importantly, grade 3-4 toxicities were reduced with low-dose lenalidomide, mainly lower neutropenia (29% vs. 41%), infections (23% vs. 31%) and venous thromboembolism (3% vs. 13%). This study supports a strategy of lenalidomide dose reduction at the outset for at-risk patients, and prospectively confirms that such an approach reduces adverse events while not compromising patient response or survival outcomes.