Treatment of older patients with multiple myeloma: towards a frailty approach

General discussion Over the last decades, the prognosis of non-transplant eligible (NTE) patients with newly diagnosed multiple myeloma (NDMM) has improved substantially.1-3 However, this benefit is less in older patients, both when treated within clinical studies as in those patients receiving standard of care.2,4-6 There are several explanations for the inferior survival of older patients with MM. Firstly, older patients more often receive doublet therapies, instead of the generally more potent triplets. Secondly, older patients experience more pronounced treatment related toxicity hampering optimal treatment, leading to relapse or may even lead to death.7 Thirdly, older patients are less likely to receive a subsequent line of treatment, which might be due to comorbidities, persistent toxicity related to former treatment, or the patient’s wish for palliation.8 Finally, older patients may receive no treatment at all because physicians feel reluctant to treat them of fear for treatment related complications.2,9,10 This in turn may lead to under-treatment of a relatively fit subgroup of patients, causing inferior outcome.11,12 In order to improve the outcome of older patients with NDMM, it is needed: I. to identify fit versus non-fit patients, in order to personalize treatment; II. to perform clinical trials to investigate the efficacy of treatment regimens in older patients according to their frailty level; III. to obtain meticulous data on side effects and quality of life (QoL), since older non-fit patients might value side effects and the effect of treatment on QoL as more important factors that impact the choice for treatment than length of life only.13,14 This thesis aimed to fill part of these knowledge gaps in the treatment of NTE patients with NDMM. In PART I we validated the current gold standard of frailty assessment in MM, the IMWG frailty index (IMWG-FI), as well as the simplified frailty index that is more commonly used in clinical trials. We refined the IMWG-FI in order to improve the prognostic value for outcome. In PART II we investigated the value of novel treatment options that were hypothesized to be suitable for non-fit older patients with NDMM. in PART III we investigated the impact of treatment on health-related quality of life (HRQoL).