The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: A prospective observational study

doi:10.21203/rs.3.rs-1025129/v1

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The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: A prospective observational study

https://doi.org/10.21203/rs.3.rs-1025129/v1

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Background

Multiple myeloma (MM) is the third most common hematologic malignancy with increasing importance due to improving treatment strategies and long-term outcomes in an aging population. This study aims to analyse influencing factors on health-related quality of life (HRQoL), such as treatment strategies, participation in a clinical trial and patient characteristics like anxiety, depression, gender, and age. A better understanding of the individual factors in context with HRQoL could provide a helpful instrument for clinical decisions.

Methods

In this prospective observational study, the HRQoL of MM patients with different therapies (first-line and relapse) was quantified by standardized questionnaires (EORTC QLQ-C30 and -MY20) in the context of sociodemographic data, individual anxiety and depressiveness (PHQ-4), and a selected number of clinical parameters and symptoms at defined time-points before, during, and after therapy.

Results

In total, 70 patients were included in the study. The median age of the study cohort was 62 years. 44% were female and 56% were male patients. More than half of the patients were fully active with an ECOG 0. Global health status was significantly higher in patients with first-line treatment and even increased after start of therapy, while the pain level decreased. In contrast, patients with relapsed MM reported a decreasing global health status and increasing pain. Additionally, there was a higher global health status in less anxious/depressive patients. HRQoL decreased significantly after start of chemotherapy in the parameters body image, side effects of treatment, and cognitive functioning. Tandem stem-cell transplantation was not found to be a risk factor for higher impairment of HRQoL. Participation in a clinical study led to an improvement of most aspects of HRQoL. Among others, increased anxiety and depression, female gender, older age, impaired performance status, and recurrent disease can be early indicators for a reduced HRQoL.

Conclusion

This study showed the importance of regular longitudinal assessments of patient reported outcomes (PROs) in routine clinical care. For the first time, to our knowledge, we were able to demonstrate a potential impact between participation in clinical trials and HRQoL. However, due to frequently restrictive inclusion criteria for clinical trials, these MM patients might not be directly comparable with patients treated within standard therapy concepts. Further studies are needed to clarify the relevance of this preliminary data in order to further an individualized, patient-centred, therapy concept.

multiple myeloma

quality of life

participation in clinical trials

depression

observational

After leukaemia and Non-Hodgkin lymphoma, MM is the third most common haematological malignancy worldwide and the probability of occurrence is age-dependent (1). As a consequence of the aging population, the importance and number of cases are rising (1). Symptoms of MM are multiform and often non-specific, such as anemia, ostealgia, fatigue, weight loss, impairment of renal function, and predisposition for infections (2). MM patients often experience multiple combinations of these symptoms. For example, a study in Denmark showed that myeloma patients experience more symptoms and problems such as pain, fatigue and constipation, problems with physical, role, and social function, than patients with other haematological cancers (3). Due to new diagnostic possibilities, the introduction of novel agents and the widespread use of high-dose melphalan with autologous stem cell transplantation (SCT) as first-line treatment, there is a higher survival rate than in the past few decades (4–6). However, MM remains an almost incurable disease and the aim of therapy is to obtain the best possible remission with prompt control of symptoms and normalization of myeloma-associated complications. In this regard considering the individual lifestyle- and disease situation and avoiding short- and long-term adverse effects of the therapy is very important. Nevertheless, as a cross-sectional postal survey of 650 patients at different disease stages showed, recovery to full functioning and symptom levels after therapy is frequently not possible (7). Another longitudinal study with 94 patients receiving high-dose melphalan and autologous SCT also confirmed that myeloma patients suffer from many severe symptoms like fatigue, pain, anxiety and depression at the beginning of the therapy. Following transplant, most symptoms disappear, but depression and overall quality of life (QoL) remained (8). Hence, despite the new therapies, myeloma remains a chronic disease where patients intermittently suffer from symptoms of the disease and treatment-related toxicity (and often facing disease progression) but can also experience intervals of disease stability throughout maintenance or even the absence of treatment for many years. Consequently, the HRQoL of patients with MM becomes more important for clinical decision making. Despite an increasing scientific focus on the topic, the results of current studies of MM and HRQoL are unclear and heterogeneous (9).

The aim of this study is to identify the most affected aspects of QoL before, during and after the different therapies of MM, and to detect influencing factors that can be taken into account when creating patient specific therapies, to enable the highest rate of QoL and to provide a basis for the consideration of those results in clinical decision making.

Study design and participants

For this prospective observational study, 70 patients with MM were recruited continuously, from April 2013 until January 2015, prior to the start of treatment at the University Hospital Wuerzburg, regardless of the individual time point of primary diagnosis. The patients were either newly diagnosed or had previously received treatment. Inclusion criteria were age ≥ 18 years, histologically proven MM, and an informed written consent. Exclusion criteria was a prior diagnosis of a second malignancy, with the exception of basalioma. The study was approved by the Medical Faculty Local Ethics Committee of the University of Wuerzburg (vote-no 301/12).

The QoL data was collected longitudinally by using the European Organization for Research and Treatment of Cancer (EORTC), Quality of Life Questionnaire-Core 30 (QLQ-C30), and the Multiple Myeloma Module (QLQ-MY20). In addition to the EORTC QLQ-C30 and QLQ-MY20, the Ultra-Brief Screening Scale for Anxiety and Depression (4-Item Patient Health Questionnaire, PHQ-4) and a sociodemographic questionnaire were employed at the first assessment to gather information about suspected influencing factors of QoL, such as mood and sociodemographic situation. Subsequently, a database was developed, which contained several clinical parameters including laboratory values, comorbidities, symptoms, used chemotherapeutic drugs, and stage of MM at the time of assessment. Furthermore, participation in a clinical trial was documented; however, there was no stratification of outcomes with respect to treatment within a trial.

The patient population (n = 70) was divided into subgroups depending on the following: first- or subsequent treatment and patients unsuitable for transplantation/high-dose chemotherapy versus patients undergoing an autologous/allogeneic SCT (single or tandem), which is shown in Table 1 in the result section.

The first assessment was conducted before the start of the therapy for all subgroups. Patients without SCT were interviewed for the second time four weeks after the end of therapy. In the case of patients with SCT, the second assessment was conducted four weeks after the end of induction but before (first) SCT. For the whole study population, the last assessment was made three months after the end of therapy.

Procedures

Each patient with an indication of first-line or relapse treatment of MM during the inclusion interval was asked for participation in this study. If interested, patients were informed that participation was voluntary and would not affect their treatment in any way, and the study design and procedures were explained. After that, written informed consent was obtained for those patients who wanted to proceed with the study.

Before the start of therapy, the sociodemographic, PHQ-4, QLQ-C30 and -MY20 questionnaires were explained to patients and completed by patients in paper format either during their clinic visits or at home. In the following assessments only QLQ-C30 and MY20 questionnaires were performed. In case of completion at home, patients received a pre-paid envelope for sending back the questionnaires to the institute. At the first assessment, clinical parameters and information on the patients’ medical history was collected from the medical notes.

Data collection and measures

With regard to HRQoL, the EORTC QLQ-C30 was used for the generic QoL and the QLQ-MY20 module for the myeloma specific aspects including disease-specific symptoms and concerns (10).

The presence of clinically relevant anxiety or depression was measured using the PHQ-4 questionnaire. This is an ultra-brief, self-report questionnaire that consisted of a 2-item depression scale (PHQ-2) and a 2-item anxiety scale (GAD-2). It was chosen because of its reliability, validity, and short response time (less than 4min). The two depression items were “little interest or pleasure in doing things” and “feeling down, depressed”. The two anxiety items were “feeling nervous, anxious or on edge” and “not being able to stop or control worrying or hopeless”. Each item was scored from 0 to 3. Therefore, the composite PHQ-4 total score ranged from 0 to 12 (11).

Sociodemographic data was assessed by a standardized questionnaire. It included information on nationality, age, gender, marital status, educational level, occupation status, sick leave, occupational disability and income.

Disease and treatment details and clinical information were extracted from medical records. These details included information at the time of primary diagnosis on staging (ISS, Salmon und Durie), time since diagnosis, previous treatments, comorbidities, CRAB criteria, cytogenetics, the immunoglobulin type, light chains, β2-microglobulin, Bence-Jones-proteinuria, M-gradient, LDH, creatinine, calcium, albumin and haemoglobin levels.

Additionally, at the respective time of assessment (3 or 4 times), details of current treatment, weight, ECOG performance status therapy with bisphosphonates or radiation were noted. The performance status was assessed by applying the ECOG scale with 0 ‘Fully active’ to 4 ‘Completely disabled’. Relevant treatment details included the type of treatment (first-line vs. treatment of a recurrent disease, suitability for transplantation/high-dose chemotherapy: no transplantation or autologous/allogeneic/tandem-SCT), the drugs used (including dose and number of cycles), and the last response to treatment. Due to frequent use of combination therapies with Bortezomib and Lenalidomide, the former standard therapy with alkylating agents, and for better comparability with other studies; current treatment was subdivided in Bortezomib-containing, Lenalidomide-containing and alkylating agent-containing.

Statistical analysis

Sample size calculation was carried out by the G*Power Program. Data were analysed using SPSS Statistics software Version 25. First, for the descriptive analysis, quantitative variables (like haemoglobin level) were characterized by using means and standard deviations, medians, first and third quartiles, minimums and maximus. Qualitative variables (like sex, symptoms and academics) were analysed using a contingency table. For all variables, missing data was reported.

In the case of small size of subgroups, the procedure was descriptive. For all other subgroups, Chi-square test, t test, Mann-Whitney U test or Fisher’s-exact-test were used to check the influence of supposed risk factors for anxiety and depression and differences in patient characteristics in the different subgroups (patients with primary diagnosis or relapse etc.).

For the analysis of EORTC QLQ-C30 and MY20 normality was tested by q-q-plots and control variables were identified by the Mann-Whitney U test. Multilevel models (also known as linear mixed-effect models) were used for testing significance.

In the case of normal distribution, the t-test was used to investigate the influence of participating in clinical trials, of anxiety/depression and of gender on HRQoL. For other distributions, the Mann-Whitney U test was performed. In the case of normal distribution, mixed ANOVA analysis was performed to explore the change of HRQoL of this clinical-trial-group over the time. Without normal distribution, a group comparison was carried out by calculating differences between the last and the first assessment and checking those difference values by the Mann-Whitney U test. In the case of normal distribution, ANOVA analysis was used to investigate the influence of age (three groups ≤ 59, 60–69 and ≥ 70 years) on HRQoL, otherwise the Kruskal–Wallis test was perfomed.

Due to the small sample size, testing normality was abandoned and the Mann-Whitney U test was used directly for the analysis of the influence of anxiety and depression on HRQoL (for the whole study population and the subgroup with tandem-SCT over the assessment time).

The significance level for the whole statistical analysis was p = 0.05.

Baseline patient and disease characteristics

The patient population (n=70) was divided into subgroups depending on first- or higher-treatment-line and suitability for autologous/allogeneic/tandem-SCT (Table 1).

Table 1: Subgroups dependent on type of treatment

24 of the 65 patients were participants of a clinical trial: 13 patients were treated within the DSMMXIV (NCT01685814), 5 within the DSMMXIII (NCT01090089), 6 within the ENDEAVOR (NCT01568866) and 1 within the PAT-SM6 antibody study (NCT01727778). 18 patients were excluded during the assessment.

The mean age was 62.6 years with a higher proportion of men taking part (55.7%). At the time of diagnosis, half of the patients had more than one comorbidity and at the beginning of the assessment almost three quarters of patients suffered from 3 or more symptoms. Nevertheless, more than half of them were fully active with an ECOG performance status of 0 points in 52.9 %.

A detailed review of patient sociodemographic data, clinical data on comorbidities, and treatment history can be found in Supplemental material Table 1. Regarding the sociodemographic and clinical characteristics, there was mostly no significant difference between the patients with first-line and relapse therapy and the subgroups with or without transplantation. As expected, the age was significantly younger in case of transplantation as first-line therapy (58.1 years) versus unsuitability for transplantation/high-dose chemotherapy (first-line 74.7 (p=0.001) and relapsed 67.4 years (p=0.010)). Additionally, patients with transplantation as therapy of relapsed MM (60.9 years) were significantly younger than patients with novel agent-based therapy without transplantation as first-line treatment (p=0.019). It was also noted that there was a significantly higher education level in patients with relapsed disease (p=0.020).

MM treatment

Consistent with the current therapy guidelines, most patients with newly diagnosed MM in this study were treated with a tandem-SCT (58,3% of patients with first-line treatment) and most patients with relapsed MM were treated with a novel agent-based therapy without SCT (52.9% of patients with treatment of a relapse). Overall, bortezomib-containing treatment was the most common therapy (67.1% of all), followed by Lenalidomide-containing protocols (55.7% of all). Before start of therapy, 10% of all patients received radiotherapy with a decreasing number in the systemic treatment process. Meanwhile, treatment with bisphosphonates increased after the start of chemotherapy (from 24.3% to 40.6%).

Most patients with relapsed MM had previously received an intensive therapy: 20.6% had more than one prior transplant, 52.9% one autologous SCT and 26.5% only conventional chemotherapy or novel agent-based therapy without SCT. In average they had received 3.2 therapies (range 1-9) before the recent treatment.

Anxiety and depression (PHQ-4)

The 4-item Patient Health Questionnaire-4 (PHQ-4) is an ultra-brief self-report questionnaire that consists of a 2-item depression scale (PHQ-2) (12, 13) and a 2-item anxiety scale (GAD-2) (14). The composite PHQ-4 score ranges from 0 to 12. Scale scores of ≥6 indicate moderate, scores ≥ 9 indicate severe psychological distress and an increased risk for a depressive or an anxiety disorder, respectively (11).

The screening for anxiety and depression by using the PHQ-4 questionnaire as part of the first assessment, showed an average value of the 70 interviewed persons of 3.27 (minimum 0.00 and maximum 12.00), which corresponds to a low-grade risk increase compared to a reference population without MM (15).

There was no significant difference in anxiety and depression of patients with first-line or relapse treatment regarding severe (p=0.358) or moderate psychological distress (p=0.768). Moreover, if considering only those patients with a score ≥ 6, there was no significant difference in age, gender, marital status, intellect, stage at diagnosis (ISS), number of symptoms and clinical findings or time since diagnosis for all patient subgroups.

HRQoL by treatment and over the course of time

All results regarding HRQoL are represented schematically in detail in Supplementary Table 2 and in summary in Supplementary Table 3. On average, patients with first-line treatment reported a significantly lower pain level and a better global health status before start of treatment, while role functioning was significantly better for patients before relapse treatment. Although there was no significant difference, most of the other parameters of HRQoL were perceived more favourable by patients with first-line treatment in comparison to patients with recurrent MM. Remarkably, in contrast to relapsed MM patients, there was an additional increase of the global health status and a decrease of pain after the start of therapy for patients with first-line treatment. However, after start of therapy, body image and cognitive functioning of all interviewed patients decreased significantly. Concurrently, except for constipation, side effects of treatment and symptom burden increased.

There was no additional significant impairment of HRQoL before, during and after therapy of patients with tandem transplantation in comparison to the other patients (patients unsuitable for transplantation/high-dose chemotherapy and patients with single autologous or allogenic SCT).

In addition, in all patient subgroups participation in clinical trials was correlated to a better HRQoL in numerous parameters at all time points compared to non-study patients. Before the start of treatment, there was a significantly better future perspective, lower side effects of treatment, higher emotional functioning, and lower fatigue of patients included in clinical trials (Fig. 1a)). Interestingly, three months after the end of treatment, there was a consistently better future perspective, significantly less constipation and less financial difficulties in patients treated in clinical trials (Fig. 1b)). Over time, the majority of these observations were most pronounced in the subgroup of patients with first-line treatment in clinical trials. Moreover, all interviewees treated in the clinical trials reported a significantly and continuously rising role functioning, compared to the other patients, who indicated a persisting decrease.

HRQoL by patient characteristics - gender

Male patients indicated a better HRQoL in most parameters than women before start of treatment. As such, they reported a better future perspective, physical, role and emotional functioning, body image, less nausea/vomiting and loss of appetite (Fig. 2a)).

HRQoL by patient characteristics - age

Although better scores in younger patients (<70 years) with MM suggest a better HRQoL before start of treatment, most parameters did not reach a significance level. None the less, these patients reported significantly less fatigue and constipation than elderly patients (Fig. 2b)).

HRQoL by anxiety and depression (PHQ-4)

Another important influence factor of HRQoL of patients with MM was anxiety and depression, measured by the PHQ-4. Patients with less anxiety/depression (especially PHQ<6) indicated a better HRQoL in almost all parameters, at all assessment times, and regardless of patient subgroups (Fig. 3a), b) and c)). Before the start of treatment, those patients with PHQ<6 reported less side effects of treatment, a better future perspective, physical, role, emotional, cognitive and social functioning, less fatigue, a better body image, less nausea/vomiting, less insomnia, less appetite loss, less financial difficulties and an overall better global health status than anxious/depressive patients (Fig. 3a)) (p-values range from <0.001 up to 0.021).

In the following section, we want to particularly address the differences between patients in first-line therapy and relapsed MM patients, which could prove beneficial for clinical routine (Fig. 3b) and 3c)). Only in the group of patients who underwent a first-line treatment, a PHQ<6, was correlated with significantly less side effects of treatment before and up to 4 weeks after treatment. Moreover, these patients perceived a better physical and role function, and less nausea and vomiting before start of the treatment than interviewees with PHQ≥6 (Fig. 3b)). Three months after therapy, only in this subgroup was insomnia persistently less common.

In contrast, only relapsed patients with a PHQ<6 reported a better body image over the entire course of treatment and less financial difficulties up to 3 month after the end of treatment than anxious/depressive patients in this subgroup. Interestingly, there was no significant difference between patients with a PHQ<6 and ≥6 with regard to appetite loss before the start of treatment (Fig. 3c)).

Considering the subgroup of the 46 patients who underwent transplant-based concepts in particular, a PHQ<6 was as well associated with better HRQoL scores over time. With the exception of appetite loss, patients with single SCT and PHQ<6, the same parameters as in all patients with PHQ<6, were performing statistically significantly superior compared to patients with a PHQ≥6 before start of treatment. Patients with mono SCT and PHQ<6 reported a better future perspective, a higher emotional/cognitive/social functioning, less fatigue, less insomnia, less side effects and a better global health status than anxious/depressive patients of this subgroup at t1 (p-values range from <0.001 up to 0.004). Moreover, they reported a higher physical and role functioning, a better body image, less nausea and vomiting and less financial difficulties compared to the patients with a PHQ≥6 in this subgroup (p-values range from p=0.001 to 0.030). In contrast to the whole study collective, this subgroup in general suffered significantly less from disease symptoms (p=0.005) and less from pain (0.012) compared to patients with a PHQ≥6 who underwent a single SCT. Many of these positive effects such as a better body image, less side effects/less disease symptoms, a better emotional/cognitive/social functioning, or fatigue, persisted until the end of treatment and for up to 3 month compared to single-transplant-patients with a PHQ≥6.

Among the 25 patients with tandem-SCT a significantly better emotional functioning was detected as well as less side effects of treatment in less anxious/depressive patients (PHQ<6) 4 weeks after induction chemotherapy. Without reaching the significance level, most of the remaining HRQoL parameters showed a trend to a better HRQoL in patients with PHQ<6.

Measuring HRQoL associated with different therapies of MM has become more important in the last years due to improvements in overall survival achieved with newer agents (5). As a consequence of these therapies, myeloma becomes a chronic disease, so the role of HRQoL increases for informed clinical decision making. With regards to available data from other studies, it seems that the new treatment approaches lead to an improvement in HRQoL scores (16). However, weaknesses and inconsistencies in the analysis and presentation of HRQoL data were observed, often complicating the interpretation of the impact of treatment on HRQoL in MM (9, 17). Further evaluation of HRQoL in MM patients under treatment is required. Therefore, this single centre study intended to contribute to a better understanding of the most affected aspects of QoL before, during and after the different types of therapy of MM. The objective was to detect important HRQoL determinants that would allow targeted improvement of individualized supportive patient care.

A central aspect of this study was to identify a suitable screening for anxiety and depression in patients with MM under the presumption that this could be an important and common risk factor for reduced HRQoL in this situation (18-20). The PHQ-4 was especially chosen because of its short response time and it was well accepted by the study collective. With an average value of 3.27, it showed an elevated risk for anxiety and depression in patients with MM, while data from a large sample of primary-care patients (without MM) showed a mean PHQ-4 score of 2.5 (11). Remarkably, patients with less anxiety and depression (especially PHQ<6) indicated a better HRQoL in almost all parameters, at all assessment times, and regardless of patient subgroups. In particular, within the subgroup of first-line patients, fewer side effects were reported, including, for example, less insomnia up to 3 months after the end of treatment. Patients with relapsed myeloma and PHQ<6 were significantly less concerned about financial aspects compared to the patients with elevated scores for anxiety and depression in this subgroup. Screening with a focus on anxiety and depression should therefore be performed early and repeatedly since an increased level of anxiety and depressiveness can have far-reaching effects on the further course of HRQoL. In particular, patients with PHQ≥6 should be offered intensive psycho-oncological support at an early stage.

Matching the HRQoL data from the randomized phase III ALCYONE trial, showed an increasing global health status and decreasing pain under therapy in patients with newly diagnosed multiple myeloma ineligible for SCT (16). This study was able to demonstrate the same effects for the subgroup of first-line patients. In contrast, we could detect opposing results in the relapse group. Most patients reported an impairment in the majority of the HRQoL parameters, especially more side effects over time with a slow recovery as the distance from therapy increased. This is consistent with the results that Dhir et al. presented at the last ASH Annual Meeting regarding SCT patients as well as the large population-based Canadian trial from Ebraheem et al. (21, 22). However, in contrast to the Ebraheem study, which included only first-line patients eligible for SCT, we tried to also focus on the differences between patients in first-line therapy and relapsed MM patients. Although results did not reach a significance level, we determined a trend towards better performance in almost all aspects of HRQoL in patients under first-line treatment. This trend could be caused by the long time from diagnosis and associated multiple pre-therapies, which reference data largely supports (23, 24). Even though we were able to include only 25 patients treated with tandem-SCT, these first results seem to be in line with the results of other research groups. Uyl‐de Groot et al. could demonstrate, that in a group of 51 patients, tandem-SCT was being subjectively well tolerated by the majority of patients with a relatively short duration of declined quality of live (25). Therefore, especially for patients who worry about their QoL regarding to this intensive therapy, this could be an informative decision support for therapy modality.

In addition, this study identified age and gender as possible influence factors for multiple aspects of HRQoL in patients with MM. These results are largely consistent with the reference data (26-28). Women seem to suffer more from physical restrictions, impaired emotional functioning, and reduced QoL before start of treatment. Elderly patients in our study reported significantly more fatigue and constipation. Mian et al. reported data from a cohort of 40 elderly patients (>65 years), who underwent stem-cell transplantation and remained stable with regards to function and overall QoL whereas the mental health of the study participants had actually improved 6 months after the end of therapy (29). If these observations were to be confirmed in larger studies, female and elderly patients might benefit from intensive and more specific supportive care in order to be able to better withstand intensive therapy concepts.

To the best of our knowledge, this is the first study, which aims to compare the HRQoL of participants of clinical trials with patients treated outside such trials. The observed improvement of many HRQoL parameters in the group of the 24 clinical trial participants compared to those treated outside a clinical trial could be due to good information given about the disease and treatment and possibly a closer connectivity to the therapeutic team. Future perspective, side effects of treatment, emotional functioning and fatigue were reported significantly better before the start of a treatment and persisted throughout the treatment timeframe. However, clinical trials have inclusion criteria, which could have led to differences in patient characteristics. Therefore, it is difficult to make a comparison of MM patients treated in clinical trials with patients treated within standard therapy concepts. Moreover, there was no explicit stratification of outcomes with respect to treatment within a trial. Nevertheless, these results should be taken into consideration in the therapy setting of patients with chronic diseases, who don’t meet inclusion criteria of clinical trials or don’t want to take part in clinical trials. In addition, these patients should also get intensive support from the help of artificial intelligence or special coaching programs, for example. There is starting to be documented evidence for the effectiveness of these forms of intensive support (30, 31).

As noted in the following section, this study has some limitations. The context of the investigation as a pilot study, at this stage, must be considered when interpreting the results. Due to the heterogeneous therapy groups, each cohort is very small and therefore the consequences are limited. Due to the small number of participants treated without novel agents (Supplementary Table 4 and 5), follow up studies are needed as a final position to HRQoL under the treatment by novel agents in comparison to conventional chemotherapy could not be taken. Additionally, we could not draw a comparison between autologous/autologous or autologous/allogenic tandem transplantation concepts. Furthermore, the median age of patients treated with autologous SCT was younger compared to other treatment groups. Therefore, any consequences taken from these results should be interpreted carefully. Finally, we only performed a single screening by PHQ-4 before the start of treatment. Instead of a single screening, patients with MM should be screened regularly for anxiety and depression to be able to provide early psycho-oncological support to improve physical and emotional functioning as well as general QoL.

This study showed the importance of regular longitudinal assessments of PROs like anxiety and depression and QoL in routine clinical care of patients with MM before, during and after systemic therapy. In our opinion, the PHQ-4 and EORTC QLQ-C30/-MY20 are suitable instruments. The early integration of psycho-oncological care and other supportive offerings, especially for anxious or depressed patients, might improve not only the QoL sustainable but also the therapeutic success during the therapy of MM.

In addition, patients under treatment of relapsed myeloma were more often confronted with reduced QoL in different dimensions, which should be taken into consideration in the choice of treatment intensity with regard to potential toxicities. On the other hand, there is an encouraging chance of improvement of global health status and pain during the systemic MM therapy for first-line patients compared to patients with relapsed MM. Even though there were limited patients in this subgroup, treatment by tandem-SCT was well tolerated in terms of QoL by the majority of the patients.

The gender and age of patients could be important aspects to consider on the way to an individualized, patient-centred therapy concept.

Irrespective of these afore mentioned limitations, we demonstrated a possible impact of participation in clinical trials on HRQoL for the first time. While further studies are needed to clarify the relevance of this preliminary data, these results are promising and more robust treatments, such as artificial intelligence and coaching programs, may accompany patient treatment programs in the future.

ANOVA, analysis of variance, CRAB, calcium level, renal dysfunction, anaemia and destructive bone lesions, DSMM, Deutsche Studiengruppe Multiples Myelom, ECOG, Eastern Cooperative Oncology Group; EORTC QLQ-C30, European Organization for Research and Treatment of Cancer (EORTC) quality of life questionnaire C30; EORTC QLQ-MY20, European Organization for Research and Treatment of Cancer (EORTC) myeloma-specific quality of life questionnaire MY20; GAD-2, Generalized Anxiety Disorder-2; HRQoL, health-related quality of life; ISS, International Staging System; LDH, lactate dehydrogenase; MM, Multiple Myeloma; PHQ-4, Patient Health Questionnaire-4; PRO, patient reported outcome; QoL, quality of life; SCT, stem cell transplantation

Ethics approval and consent to participate

This study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki. The study protocol, informed consent forms, and other study-related documents were reviewed and approved by the local ethics committee of the Medical Faculty of University of Wuerzburg (votum-no 301/12). Written informed consent was obtained from all patients. All methods were carried out in accordance with relevant guidelines and regulations.

Consent for publication

Not applicable.

Availability of data and materials

The datasets generated, used and analysed during the current study are available from the corresponding author on reasonable request.

Competing interests

The authors declare that they have no competing interests.

Funding

This publication was supported by the Open Access Publication Fund of the University of Wuerzburg. No Funding other than that.

Authors' contributions

CL, JF, SD and SK contributed to the study conception and design. Data collection, assembly of Data and Data interpretation were performed by JF. Data analysis was carried out by DK. The first draft of the manuscript was written by JF and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Acknowledgements

We thank the patients who participated in this study. Support in sample size estimation and choice of suitable measuring instruments/questionnaires was provided by Prof. Dr. med. Dr. phil. Faller, department of medical psychology and psychotherapy, medical sociology and rehabilitation sciences, institute of epidemiology and biometrics, Julius Maximilian University of Wuerzburg. Statistical support was provided by Dr. Malzahn/Mrs. Haas, chair of clinical epidemiology and biometrics, Wuerzburg; Mrs. Keller, statistics and consultation, Kürnach.

Author details

¹ Department of Pediatrics, Wuerzburg University Medical

Center, Josef-Schneider-Straße 2, 97080 Wuerzburg, Germany.

² Department of Haematology and Oncology, Wuerzburg University Medical

Center, Oberdürrbacher Straße 6, 97080 Wuerzburg, Germany.

³ “Daniela Keller – Statistik und Beratung“, Prosselsheimer Straße 4, 97273 Kuernach, Germany.

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No competing interests reported.

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The influence of baseline characteristics, treatment and depression on health-related quality of life in patients with multiple myeloma: A prospective observational study

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Background

Methods

Study design and participants

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Statistical analysis

Results

Baseline patient and disease characteristics

MM treatment

Anxiety and depression (PHQ-4)

HRQoL by treatment and over the course of time

HRQoL by patient characteristics - gender

HRQoL by patient characteristics - age

HRQoL by anxiety and depression (PHQ-4)

Discussion

Conclusions

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