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Letters to the Editor
Symptom burden in transplant-ineligible patients with newly diagnosed multiple myeloma: a popula- tion-based cohort study
Multiple myeloma (MM), a neoplasm characterized by the clonal proliferation of malignant plasma cells, is asso- ciated with major morbidity and mortality. The median age at diagnosis is 70 years, making MM a disease of older adults. While much progress has been made in the therapeutics for newly-diagnosed multiple myeloma (NDMM) patients, including transplant-ineligible patients, MM remains an incurable malignancy. Both the disease of MM itself, as well as the treatments initiated, likely impact patients’ quality of life and their burden of symptoms. To date, there has been no large population study conducted in adults with NDMM, specifically transplant-ineligible patients, examining the effect of symptom burden over time and associated factors.
In 2007, as part of an initiative to improve symptom management, routine prospective collection of a patient- reported outcome, the Edmonton Symptom Assessment System (ESAS) score, during all outpatient cancer clinic visits was started in Ontario, Canada. The ESAS is a val- idated and reliable patient-reported outcome tool that is used to assess common cancer-associated symptoms.1 It consists of nine symptoms, namely tiredness, impaired well-being, pain, drowsiness, loss of appetite, anxiety, shortness of breath, depression and nausea, which are scored by the patients on a numerical rating scale from 0 (no symptoms) to 10 (worst possible symptoms). We conducted a longitudinal study of ESAS data in order to examine symptom trajectory and determine factors asso- ciated with moderate to severe symptoms in the first year following diagnosis among transplant-ineligible adults with NDMM receiving treatment between 2007-2018.
Table 1. Characteristics of multiple myeloma patients who reported at least one Edmonton Symptom Assessment System score in the first 12 months following diagnosis.
Characteristics
Age, years; median (IQR)
Male; n (%)
Geographic region; n (%) Urban
Rural
Socioeconomic status, poor; n (%)
Charlson Co-morbidity Index; n (%) ≤1
(N=2876)
74 (70-80)
1,649 (57.3)
2,473 (86.0) 403 (14.0)
464 (16.1)
2,478 (86.2) 398 (13.8)
953 (33.1)
1,923 (66.9)
911 (31.7) 130 (4.5) 304 (10.6) 752 (26.2)
39 (20-87)
35 (14-79)
676 (23.5)
2,200 (76.5)
2,146 (74.6) 688 (23.9)
2,349 (81.7)
≥2
Multiple administrative healthcare databases in the universal, single-payer, publicly funded system in Ontario, Canada were linked using a unique encrypted patient identifier and analyzed at ICES (formerly known as the Institute for Clinical Evaluative Sciences). ICES is an independent, non-profit research institute whose legal status allows it to collect and analyze healthcare and demographic data without consent for health system evaluation and improvement. The study was approved by the ethics committee of McMaster University and fol- lowed data confidentiality and privacy guidelines of ICES.
Year of diagnosis; n (%) 2007-2012
2013-2018
Myeloma end-organ damage*; n (%) Anemia
Hypercalcemia
Bone disease
Renal failure
Time from diagnosis to treatment, days; median (IQR)
Time from diagnosis to first recorded ESAS score; median (IQR)
Hospital type; n (%)
Teaching
Non-teaching
Novel agents; n (%) Proteasome inhibitor Immunomodulatory agent
Patients alive at 1 year; n (%)
All adults (age ≥18 years) with a new diagnosis of MM (International Classification of Diseases for Oncology, 3rd Edition, histology code 9732) between January 2007 and December 2018 were identified. Patients’ demographics (age, sex) were extracted. Baseline co-morbidities were recorded using the modified Charlson-Deyo Comorbidity Index (CCI) within 1 year prior to the date of diagnosis.2 Socioeconomic status was determined using a validated modified Ontario Marginalization Index.3 Myeloma- related end-organ damage was defined as previously described by Fiala et al.4 Treatment center (non-teaching vs. teaching) was defined as the center in which the patient first received MM treatment. Treatment receipt was defined as not having received a transplant but hav- ing received therapy with one or more of the following agents: oral cyclophosphamide/melphalan (often used in combination with steroids) or novel agents (thalidomide, lenalidomide or bortezomib often used in combination as thalidomide/melphalan/prednisone, lenalidomide/dex- amethasone, bortezomib/melphalan/prednisone or cyclophosphamide/bortezomib/dexamethasone) within
*Patients could have more than one ‘CRAB’ feature. IQR: interquartile range; ESAS: Edmonton Symptom Assessment System.
1 year of diagnosis; the above anti-myeloma drugs encompass all funded cancer drugs available to patients during the study period.
Symptoms were assessed using the ESAS score which consists of the nine symptoms described previously. We considered ESAS scores of ≥4 (moderate or severe) as being clinically relevant because they have been previ- ously shown to identify a clinically significant burden.5 For the final cohort creation, only transplant-ineligible patients who received MM treatment as defined above and reported at least one ESAS assessment in the 12 months following the date of diagnosis were included. All analyses were conducted using the Statistical Analysis System (SAS version 9.4).
A total of 4,610 transplant-ineligible patients who received treatment for NDMM were identified, of whom 2,876 (62.3%) completed at least one ESAS assessment following diagnosis and were included in the final cohort. In this final cohort, a total of 27,701 unique ESAS assess- ments were captured. Patients recorded a median of 15 ESAS assessments in the first year (interquartile range [IQR] 9-29). The baseline characteristics of the cohort are detailed in Table 1.
The trajectory of moderate to severe symptoms in each month following diagnosis is shown in Figure 1. For most symptoms, a high proportion of the cohort reported moderate to severe symptoms at diagnosis, with tired- ness (64%) and impaired well-being (60%) being among
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