Over the last decade, the introduction of newer targeted therapies has dramatically improved survival in Multiple Myeloma (MM) [
1]. However, the identification of the “best” therapeutic approach for MM remains a major clinical challenge. Despite the efficacy of the novel agents, the occurrence of relapse or progression is inevitable for the majority of MM patients, including those who respond to first-line therapies. Therefore, the treatment of relapsed/refractory multiple myeloma (RRMM) presents unprecedented challenges due to the variety of treatment options on one side and the heterogeneity of diseases at relapse on the other, with the absence of clearly defined biological-based recommendations [
2]. The choice of salvage therapy for patients with RRMM requires a careful evaluation of possible achievable clinical benefits and potential toxicities of treatments that might negatively impact on patients’ health related quality of life (HRQOL). In this scenario, the evaluation of patient-reported well-being and symptoms becomes a critical component of patients’ care management.
Rationale and clinical significance
The choice of treatment for MM patients has been traditionally focused on chronologic age and performance status, as surrogate markers for frailty [
5]. Predicting outcomes in this population is critical and recent data has pointed out the limitations of traditional prognostic indicators, by emphasizing the role of geriatric assessment [
6]. Palumbo and colleagues [
6] demonstrated that geriatric assessment (i.e., the Katz Activity of Daily Living [ADL] [
7], the Lawton Instrumental Activity of Daily Living [IADL] [
8] and the Charlson Comorbidity Index [CCI] [
9]) adds independent prognostic information for risk of death, progression, adverse events and treatment discontinuation regardless of type of therapy and the International Staging System (ISS) in newly diagnosed MM patients. Based on this key finding, Palumbo and colleagues developed the frailty score system [
6] which combines factors such as age, comorbidities, cognitive and physical conditions of patients. Importantly, the International Myeloma Working Group (IMWG) proposed this score for the measurement of frailty in the treatment decision-making process thus widely supporting its use in routine practice (
http://imwg.myeloma.org).
Although this important evidence indicates the need to enlarge the spectrum of prognostic factors that are considered relevant in MM patients, the frailty score does not include PROs, so as defined by the US Food and Drug Administration (FDA) [
10]. A novel finding in the science of prognostication in oncology has been the evidence that PROs, such as symptoms or functional limitations, could also provide prognostic information for survival or other clinical outcomes in patients with advanced disease [
11,
12].
Therefore, based on this compelling evidence stemming from the scientific literature, we will primarily investigate the prognostic value of baseline PROs for overall survival, beyond the frailty score [
6], to possibly devise a patient-centric frailty score for RRMM patients. Although the frailty score was developed in newly diagnosed (elderly) patients enrolled in RCTs, and we are aware of the differences with the population that we will be enrolled in our study, it is possible that the prognostic value of this score might also hold true in a population that, per se, is even more frail than the study in which this score was developed [
6]. The identification of PROs with independent prognostic value in RRMM has the potential to provide a strong rationale for a more patient-centric approach in routine practice. For example, it would greatly support the inclusion of a standard PRO assessment at the time of deciding type of salvage therapy. Based on previous findings in MM patients [
13,
14] and in patients with other advanced hematologic malignancies [
15], self-reported fatigue will be regarded as the primary outcome for prognostic factor analyses in this study. Furthermore, in a second instance, other PROs will also be investigated to determine whether they provide more accurate prognostic information than fatigue.
Another broad objective of CLARITY is that of generating data that may facilitate physicians to more effectively communicate with their patients and to better respond to individual needs and preferences. In situations for which several different treatment options are available, as it is the case for salvage therapies, and the choice of strategy depends on individual patient characteristics and preferences, shared decision making has been advocated [
16,
17]. Shared decision making between patients and physicians may result in a variety of benefits, including increased patient satisfaction and improved clinical outcomes [
18‐
20]. Ideally, patients should be encouraged to participate in decision-making with accurate knowledge about the risks and benefits of all the potential treatment options [
21]. However, empirical work suggests that a collaborative treatment strategy might not be ideal for all patients [
22,
23], for example, in older patients with more advanced diseases and reduced health conditions [
24,
25]. Therefore, physicians should empathetically invite patients to engage to the maximum extent they desire in making treatment decisions [
26]. Understanding the extent to which RRMM desire to be involved in making treatment decisions and how this perception is concordant with the understanding of their physicians is important to lay the groundwork for the development of more effective communication strategies. The majority of studies in this area have focused on breast cancer patients [
27,
28] and other cancer populations [
22] and there is a dearth of information on this topic for patients with MM. The very few studies that have examined this issue in MM patients have been limited by small sample size [
29] hampering definitive conclusions.
In addition, previous studies have shown that patient with advanced hematologic malignancies highly value HRQOL issues and pointed out the importance of investigating how patient’s HRQOL relate to treatment choices [
21]. The emphasis placed by physicians on HRQOL considerations, when considering various alternatives, is unknown as is whether it is different from the emphasis placed on this issue by their patients. Do RRMM patients value HRQOL issues more than their treating physicians when considering alternative treatments? Although it has been hypothesized that older adults with MM may prioritize HRQOL issues over other traditional clinical endpoints [
30], there is currently little evidence-based information and research efforts are needed in this area.
The challenge of conveying prognostic information on survival is another challenge often addressed in this setting. Physicians often face difficulties in prognostic discussions with their patients and this is particularly true in the setting of advanced cancer populations with poor prognosis [
31]. Therefore, another objective of this study is to assess the proportion of RRMM patients who seeks this information and try to identify socio-demographic and clinical factors associated with desire for prognostic information.
Finally, satisfaction with information provision will also be examined in this project, as an important component of the clinical decision-making process. Patients should be offered high-quality information about their disease and possible treatments options, including the short-term and long-term consequences of treatment.
Patient information is a crucial component of cancer care and rehabilitation [
32]. For example, there is some evidence that patients who are well-informed about their cancer report reduced level of psychological burden, improved HRQOL outcomes and satisfaction with care [
33]. Information can reduce anxiety, help develop coping skills and enhance recovery [
34]. Satisfaction with information provision has been shown to be associated with improved HRQOL outcomes in some cancer populations [
35], but this relationship has not been investigated in RRMM patients receiving modern therapies.