Quality of life assessment & out-of-pocket expenditure in multiple myeloma: An observational study

Multiple myeloma (MM) is a disease of malignant plasma cell and is the second most common haematological malignancy after non-Hodgkin’s lymphoma. Incidence of myeloma is higher in industrialized nations1 (2-4 per 100,000 population) and lower in Asia (1.7 per 100,000)2. In India, the incidence is 1.2 per 100,000 with males being affected more [1.36, 95% confidence interval (CI) 1.29-1.45] compared to women (0.99, 95% CI 0.93-1.07)3. There is heterogeneity in the incidence of MM across India. A study of 1916 cases from 27 population-based cancer registries revealed highest incidence in Southern zone (44.9%), followed by Northern zone (20.5%), West zone (19.4%), Northeast zone (9.6%), East zone (3.5%) and 2.1 per cent in Central zone4.

There has been significant improvement in the survival of myeloma patients aged ≤65 yr in the past two decades, attributed to the introduction of novel agents (immunomodulators such as thalidomide, lenalidomide; proteasome inhibitor such as bortezomib), high-dose chemotherapy, followed by autologous stem cell transplantation (ASCT), and use of maintenance therapy4. Currently, standard treatment approach for a newly diagnosed patients of myeloma (who do not have major comorbidity and are <65-70 yr of age) includes initial induction therapy with three drugs (typically bortezomib plus lenalidomide or thalidomide and dexamethasone for 4-6 cycles). Those having good response (complete/very good partial/partial response) are counselled for ASCT followed by maintenance therapy – usually lenalidomide in low doses for three years. Those who are elderly or have major comorbidities are given induction with two drug combinations (e.g. bortezomib+dexamethasone or lenalidomide+dexamethasone) for 8-12 cycles followed by maintenance therapy. Despite initial good responses in most patients relapses are frequent, with progression-free survival of 32-36 months, for those who undergo ASCT compared to less than two years for others5. The factors such as International Staging System (ISS) stage (stage III), high-risk cytogenetics, more than one line of induction therapy and presence of extramedullary disease are considered to be predictors of relapse4.Thus, in a typical case of MM, the disease course is characterized by remissions and relapses5.With each relapse, there is a reduction in the response rate as well as in the duration of response with increase in therapy-related adverse effects with impaired quality of life (QoL). Therefore, controlling symptoms and improving QoL are important considerations in the management of MM patients.

In addition to QoL, out-of-pocket expenditure (OOPE) is another important aspect in MM. The National Sample Survey Organisation (NSSO) 75^th Round Annual Report has shown that the average medical expenditure per hospitalization is different in different types of hospital with average expenditure being ₹61,216 (being lower in public hospitals ₹22,520 compared to ₹93,305 in private hospitals6. As per multicentric study on the treatment cost among cancer patients in public hospitals from five different States (Kerala, Maharashtra, Rajasthan, West Bengal and Mizoram), 75 per cent patients had financial problem and 44 per cent had to travel long distances to reach to the hospitals7. Free diagnosis and financial help towards travel expenses were suggested to improve compliance to therapy for patients belonging to economically weaker sections7.

The present study was thus conducted to assess the QoL and economic burden among MM patients being treated in a tertiary care hospital in north India. The factors affecting health-related QoL also were explored. The OOPE incurred on the treatment to understand financial difficulties faced by these patients and their families was also evaluated.

Material & Methods

This was an observational, cross-sectional study conducted in the outpatient department (OPD)setup of the department of Medical Oncology, BR Ambedkar Institute Rotary Cancer Hospital, All India Institute of Medical Sciences, New Delhi, India, between November 15, 2019 and January 30, 2020. Consecutive patients of MM attending myeloma clinic were screened for inclusion criteria. Those with definitive diagnosis of MM (based upon serum and/or urine electrophoresis, skeletal survey and bone marrow plasmacytosis), age >18 yr, patient undergoing active treatment with novel agents-based induction with or without radiotherapy or those who have undergone ASCT and currently on salvage therapy due to relapse or on maintenance therapy or patients with relapse and currently on salvage treatment were included. Those with major psychiatric disorder (patients with bipolar disorder, major depressive disorder and schizophrenia) were excluded. Severely ill patients (those who were bed ridden or unable to communicate to the interviewer due to progressive disease) were also excluded.

The study was approved by Institutional Ethics Committee (IEC-675/6.09.2019, RP-41/2019). Before taking consent, the participants were explained the purpose of the study and implications in detail. The participation was voluntary, and participant could exit from the study at any point of time. Patient signed an informed consent form before data collection which was done in private and confidentiality was maintained.

The study outcomes QoL and cost of treatment were quantitative. After review of literature in the Indian context89, the standard deviation (SD) was taken as 21, alpha error as five per cent and taking precision at four per cent and after adjusting for 10 per cent non-response rate, the sample size was calculated to be 116.

Results

A total of 116 patients were eligible for analysis. Patients’ baseline characteristics are given in Table I. The median age of the patients was 59 yr, ranging from 21 to 78 yr and 24 per cent were females; 64.7 per cent of patients had ISS stage III. Myeloma subtypes included IgG (kappa and lambda) 51.7 per cent, IgA (kappa and lambda) 8.6 per cent, and light chains (kappa and lambda type) in 25 per cent of patients. The median time from onset of symptoms to diagnosis was 30 months, ranging from two to 219 months and 20.7 per cent had two or more comorbidities; most common were hypertension (30.2%), diabetes mellitus (18.1%) and hypothyroidism (11.2%).

Income details: Ninety one (78.4%) patients were from outside Delhi; this included patients from neighbouring States of Uttar Pradesh (29.3%), Bihar (20.7%) and Haryana (12.9%). The median household expenditure was ₹20,000 (IQR, ₹2000-70,000); for those from urban area, it was ₹25,000 (IQR, ₹3000-70,000), while for patients from rural areas, median household expenditure was ₹20,000 (IQR, ₹2000-60,000).

Discussion

In the present study, the QoL and OOPE in myeloma patients were assessed during the various phases of treatment. The QoL scores in our study were higher than the respective reference values. The functioning scores were high suggesting better functioning of myeloma patients and bone pain being the most common symptom. The study also analysed OOPE and financial difficulties (part of QoL).

Patients’ characteristics were similar to those described in earlier studies. However, a few differences were observed, median age in our patients’ population was 59 yr, this was lower than those reported from North America (67-71 yr) and Europe. This possibly reflects population structure in India as almost 65 per cent of population is below 35 yr4. Chang et al15 have shown median comparable age from different countries; median age of 55 yr in India is comparable to 65 yr in the USA.

A higher proportion of patients had ISS stage III disease (61.3%) in the present study similar to earlier studies from India (45%)9 but was higher than those reported in studies from Europe (42%) and North America (17%)1617. Compared to women, men were more affected, a finding similar to earlier studies171819.

In the present study, QoL mean score was 59.6, slightly higher compared to reference value of 55.7 in EORTC QLQ C-30 global health status/QoL score11. This was similar to a study from south India (mean scores 55.3)9. Three European studies- one from France17 (mean score 57.8), Greece16 (mean score 62.6), and Denmark (mean score 61)20 have also reported similar results. A population-based study of Eindhoven Cancer Registry from Southern Netherland reported mean QoL score of 5521, while mean score was 63.3 in a patients’ self-reported study from Ireland19. Difference in score in above studies could possibly be due to inclusion of patients in different phases of treatment. A significant proportion of patients in the present study were on maintenance phase after completing primary treatment and were likely to be symptom free or have minimal symptoms.

The present study showed higher mean score for emotional functioning (81.9) indicating that the patient was less tense, depressed, irritable and worried followed by cognitive functioning (78.9) which refers to patient having less difficulty in concentrating and remembering things. Similar findings were reported in studies from Denmark20 and the Netherlands21. Other studies have shown higher cognitive functioning score followed by emotional functioning91722.

In the present study, the most common symptoms (score) were pain (39.8), fatigue (38.6) and dyspnoea (26.1). In a French study also, fatigue (49.3) was the most common symptom followed by pain (39.4) and dyspnoea (31.8)17. Similar observations have been reported in other studies1119.

Financial difficulties regarding treatment may vary from one healthcare system to another depending upon facilities and type of insurance available. While in most developed nations, health care is free or insurance covered, in low- and mid-income countries, health care is partially funded, some patients may get re-imbursement from the government or their employers, but largely patients and their families have to pool funds for the treatment. Thus, there is higher mean score in the present study for financial difficulties (29.3), compared to EORTC reference value of 16.6 which was expected. This was similar to a study from south India (28.6)9. In our study, 63.8 per cent of patients had financial difficulties, higher than that reported from Ireland (42%)19.

The disease-specific scoring by QLQ MY 20 data revealed disease symptom score of 27.87±25.1 and future perspective score of 78.2±25.7, indicating that patients were worried about dying and their health in the future. These observations were comparable to those reported in a study from south India (20.7±18.7 and 81±23, respectively)9. Unlike the present study, a multicentric study from the UK23 reported higher disease symptoms burden and lower future perspective (mean score 64.6) than our study; this study had included both newly diagnosed and relapsed/refractory cases of myeloma23.

We also evaluated correlation between QLQ C 30 global health score and four domains of QLQ MY 20; there was a negative correlation between global health score and side effects (−0.53) and a positive correlation was seen in global health and future perspective which is 0.41, which was similar to result from a French study 0.4617.

An effort was made to determine factors associated with global health status/QoL score. Myeloma stage (ISS III) and adverse effect of treatment were important predictors. These results were similar to a French study17 which showed adverse effect occurred in early phase of treatment and declined as treatment continued. Similar observations were made in a study by Robinson et al24, showing QoL association with staging and performance status. Ramsenthaler et al23 did not find correlation between survival, ISS staging and treatment related variables with QoL.

In the present study, medicine cost comprised 61 per cent of total cost and expenditure towards investigations and transport was 12 and 19 per cent, respectively. These results were similar to a study among cancer patients where drug cost was 73.9 per cent and cost towards investigation and transport was 13.2 and 10.3 per cent, respectively8. Another study from India conducted among cancer patients in few selected tertiary care hospitals of five different States showed that more than three-fourth of patients experienced financial burden which delayed their decision to treatment, 39 per cent borrowed money, while in our study, the contribution made by own family and relatives was 57.7 per cent2.

The major limitation of our study was that cost estimate made here was applicable to a public hospital, and these figures were likely to be different for patients being treated in corporate hospitals and those having insurance. There was a possibility of recall bias as details on cost were for the last 30 days and the medicines cost also included cost of medicine for comorbidities. The study did not consider caregiver perspective and their wage loss while accompanying patients.

In conclusion, our study suggests that measurement of QoL of MM patients on treatment should be done on a regular basis. It is a critical guide for a chronic disease such as MM management by treating physician and to create support system by family and friends. To deal with the problem of financial concern of poor families, there should be good referral system as well as provision of free diagnosis, low medicines cost and treatment cost and support of travel and lodging of poor patients.