Purpose
The quality of patient-reported outcome (PRO) data can be compromised by non-response (NR) to scheduled questionnaires, particularly if reasons for NR are related to health problems, which ...may lead to unintended bias. The aim was to investigate whether electronic reminders and real-time monitoring improve PRO completion rate.
Methods
The population-based study “Quality of life in Danish multiple myeloma patients” is a longitudinal, multicentre study with consecutive inclusion of treatment-demanding newly diagnosed or relapsed patients with multiple myeloma. Education of study nurses in the avoidance of NR, electronic reminders, 7-day response windows and real-time monitoring of NR were integrated in the study. Patients complete PRO assessments at study entry and at 12 follow-up time points using electronic or paper questionnaires. The effect of the electronic reminders and real-time monitoring were investigated by comparison of proportions of completed questionnaires before and after each intervention.
Results
The first 271 included patients were analysed; of those, 249 (85%) chose electronic questionnaires. Eighty-four percent of the 1441 scheduled PRO assessments were completed within the 7-day response window and 11% after real-time monitoring, achieving a final PRO completion rate of 95%. A significant higher proportion of uncompleted questionnaires were completed after the patients had received the electronic reminder and after real-time monitoring.
Conclusions
Electronic reminders and real-time monitoring contributed to a very high completion rate in the study. To increase the quality of PRO data, we propose integrating these strategies in PRO studies, however highlighting that an increase in staff resources is required for implementation.
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BFBNIB, CEKLJ, DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, INZLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NMLJ, NUK, OBVAL, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK, VKSCE, VSZLJ, ZAGLJ, ZRSKP
Immunoparesis (hypogammaglobulinemia) is associated to an unfavorable prognosis in newly diagnosed Multiple myeloma (MM) patients. However, this finding has not been validated in an unselected ...population-based cohort. We analyzed 2558 newly diagnosed MM patients in the Danish Multiple Myeloma Registry representing the entire MM population in Denmark from 2005-2013. Two-thousand two hundred and fifty three patients (90%) presented with reduction below lower normal levels of at least one uninvolved immunoglobulin. Using multivariable Cox regression we found that high age, high ISS score, high LDH and IgA MM were associated to both shorter overall survival and progression free survival. Furthermore, bone marrow plasma cell % was associated to short progression free survival. Immunoparesis had no independent significant effect on OS (HR 0.9 (95%CI: 0.7;1.0; p = 0.12)). Likewise, the number of suppressed immunoglobulins or the relative degree of suppressed uninvolved immunoglobulins from lower normal level (quantitative immunoparesis) was not associated to OS in the multivariable analysis. However, quantitative immunoparesis with at least 25% reduction (from lower normal level) of uninvolved immunoglobulins was associated to shorter PFS for the entire population. The impact of quantitative immunoparesis on PFS was present irrespective of calendar periods 2005-2008 and 2009-2013. Our population-based study does not confirm that immunoparesis at diagnosis is an independent prognostic factor regarding OS. However, quantitative immunoparesis is associated to a shorter PFS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Standard therapies for patients with newly diagnosed multiple myeloma (NDMM) who are ineligible for autologous stem cell transplantation (ASCT) have been lenalidomide-dexamethasone (Rd), ...bortezomib-lenalidomide-dexamethasone (VRd) or bortezomib-melphalan-prednisone (VMP). The benefit of adding an anti-CD38 monoclonal antibody (mAb) to the standard treatments of VMP and Rd has been demonstrated in two large phase 3 studies, achieving overall response rates (ORR) of 90.9% and 92.9% in the daratumumab-VMP arm and the daratumumab-Rd arm, respectively (Facon, 2019, Mateos, 2018). Isatuximab is an anti-CD38 mAb approved in combination with pomalidomide-dexamethasone and carfilzomib-dexamethasone to treat relapsed/refractory MM. The drug has also shown clinical responses as combination therapy to treat NDMM (Trudel, 2019). Corticosteroids have been the backbone of most myeloma-targeted therapies since the discovery of their effectiveness. Due to the continuous treatment paradigm, the cumulative dose of corticosteroids in patients is substantial. Steroids inflict reduction in both short- and long-term quality of life and increase patients' receptiveness to infections. Infections are one of the main reasons for complications and death during active first line treatment and the rate rises with age (Mothy, 2019). Instead of reducing or removing corticosteroids, isatuximab will replace corticosteroids to evaluate the effectiveness and safety of the novel regime of isatuximab-bortezomib-lenalidomide. Aim: The study will evaluate isatuximab (Isa) in combination with bortezomib (V) and lenalidomide (R) with minimal dexamethasone (d) as first-line treatment in transplant-ineligible patients. The primary endpoint is the number of patients who achieve measurable residual disease negative (Euroflow NGF 10 -5) complete response during and/or after 18 cycles of study treatment. Secondary endpoints include progression free survival, overall survival, overall response rate, safety evaluations and patient-reported outcome. Methods: The REST study is an academic, single arm, open-label, phase 2 study of NDMM patients ineligible for ASCT. 51 patients are included and receive Isa-VRd (Isa: 10 mg/kg IV Days 1, 8, 15, 22 during cycle 1, Q2W cycle 2-18; V: 1, 3 mg/m 2 SC Days 1, 8, 15 during cycle 1-8; R: 25 mg PO Days 1-21 during all cycles; d: 20 mg PO Days 1, 8, 15, 22 only for the first 2 cycles), all 28-day cycles. Results: Recruitment was completed in January 2023. Baseline characteristics, safety summary and preliminary results can be found in Table 1. The median age is 77 years, range 70-88 years. Twenty-nine patients developed 60 grade >3 non-hematological adverse events (AE), including infections (n=26), syncope (n=5), diarrhea (n=4), skeletal pain (n=4), arrhythmias (n=3), acute renal failure (n=3), increased transaminases (n=3), venous thromboembolism (n=2), arthritis (n=2), gastrointestinal hemorrhage (n=2), peripheral sensory neuropathy (n=2), edema (n=1), hyperglycemia (n=1), rash (n=1) and opiate intoxication (n=1). At a median follow up of 12 months, the ORR was 100% (51/51) with very good partial response or better at80.3% (41/51). Forty-four patients are still on study. One patient died from septicemia with staphylococcus aureus, four patients discontinued due to disease progression, one patient due to poor compliance and one patients for safety reasons judged by the investigator. Conclusions: Isa-VRd in the transplant ineligible population with a median age of 77 years has a tolerable safety profile. Isa-VRd is showing encouraging preliminary efficacy in NDMM ineligible for transplant. Follow-up is ongoing. Acknowledgements: Sanofi funded this research.
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IJS, IMTLJ, KILJ, NLZOH, NUK, SAZU, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: The severe, acute respiratory syndrome, coronavirus 2 (SARS-CoV-2), leading to coronavirus-19 (COVID-19), was detected for the first time in Wuhan, China in December 2019. In general, ...governments and health authorities have taken precautions during the COVID-19 pandemic to reduce viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have an increased risk of being infected with COVID-19 and developing a fatal course due to the MM-related immunodeficiency (Glenthøj, A et al. PMID: 32939853). To some extent, the COVID-19 pandemic has changed standard of care towards extended use of oral regimens and limiting hospital visits (Terpos E et al.PMID: 32444866).
We aimed to investigate the quality of life (QoL) of Danish patients with MM during the COVID-19 pandemic. We hypothesized that patients living alone and those under the age of 65 years, as a consequence of the pandemic, would experience impaired QoL due to social isolation and fear of infection with SARS-CoV-2.
Methods: The Danish prospective, nation-wide, observational survey “Quality of life in Danish patients with multiple myeloma” (QoL-MM) (Nielsen LK et al. PMID: 30656677) framed our study. In QoL-MM, survey data are obtained at enrolment and subsequently at 12 follow-up time points over a two-year period. The following PRO questionnaires are used; the cancer-generic instrument of European Organisation for Research and Treatment of Cancer Quality of life (EORTC) QLQ-C30 (EORTC QLQ-C30), the Multiple Myeloma module QLQ-MY20 (EORTC QLQ-MY20), the Chemotherapy-Induced Peripheral Neuropathy module (EORTC QLQ-CIPN20) and the Short-form health survey version 2 (SF12v2).
In the present study, a subpopulation of the QoL-MM cohort was constructed, based on the response time of the questionnaires. QoL was compared using patient-reported outcome (PRO) data obtained before and during the COVID-19 pandemic at group level.
In a Danish context, first wave was defined as April to June 2020 and the second wave as November 2020 to January 2021. The QoL data were analyzed using mixed effects linear regression, with a year-period-interaction. Pre-COVID versus COVID mean domain score difference was considered evident, if the difference was both statistically significant (p-value <0.05) and clinically relevant, using minimal important difference (MID) defined as 0.3 standard deviation of the mean score.
Results: The study included 616 patients (63% newly diagnosed and 37% relapsed) with a mean age of 68.2 years (standard deviation, 9.2); 40% were females; 76% were married/cohabiting, and 24% single. Questionnaire completion rates during the investigated periods were between 96% and 97%. In total, 1,685 completed sets of questionnaires were included in the analyses. The patients reported no statistically significant and clinically relevant difference in QoL during the first and second waves of the COVID-19 pandemic, compared to one year earlier, see table 1.
When analyzing the subpopulations, we found that patients below 65 years reported improved physical health summaries (p-value 0.016), decreased fatigue (p-value < 0.001), less insomnia (p-value 0.002) and improved role functioning (p-value <0.001) during the first wave, reaching both statistical significance and the threshold of MID. The group of patients living alone reported improved role functioning during the first wave, reaching both statistical significance (p-value <0.001) and the threshold of MID. These findings were not evident during the second wave, see table 1.
Conclusion: As a group, Danish patients with MM did not report impaired QoL during the COVID-19 pandemic. In contrary, we observed improvements in some domains in patients below 65 years. Our observations indicate that the patients with MM have felt cared for and in good hands during the first and second waves of the COVID-19 pandemic. However, part of the reason for our finding of no negative impact on QoL by the pandemic could be that the questionnaires used were not developed to capture the impact of the pandemic on QoL.
Importantly, our results suggest that QoL data collected in clinical trials during the pandemic allow interpretation without adjusting for the impact of the pandemic.
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Redder: Janssen-Ciliag: Research Funding. Frederiksen: Alexion: Research Funding; Gilead: Research Funding; Abbvie: Research Funding; Janssen Pharmaceuticals: Research Funding; Novartis: Research Funding.
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IJS, IMTLJ, KILJ, NLZOH, NUK, SAZU, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
The aetiology of multiple myeloma (MM) is unknown but various environmental exposures are suspected as risk factors. We present the first paper analysing the geographical distribution of ...MM in Denmark at the municipal level to investigate variations that could be explained by environmental exposures.
Methods
Patients diagnosed with MM in Denmark during 2005–2020 were identified from nationwide registries and grouped into the 98 Danish municipalities based on residence. The age‐ and sex‐standardised incidence rate (SIR) of each municipality was compared to the national incidence in a funnel plot with 95% control limits. Differences in SIRs of rural, suburban, and urban areas were evaluated with incidence rate ratios.
Results
In total, 5243 MM patients were included. Overall, we found a heterogeneous geographical distribution of MM and a potential hotspot in southern Denmark. This hotspot contains three municipalities with SIRs above the 95% control limit assuming considerably higher rate of MM compared to the national incidence rate. A significant higher SIR was found in rural areas compared to urban areas.
Conclusion
The geographical distribution of MM in Denmark indicates that the risk of developing MM depends on place of residence probably due to environmental factors.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, SIK, UILJ, UKNU, UL, UM, UPUK
In general, governments and health authorities have taken precautions during the COVID-19 pandemic to reduce the viral spread and protect vulnerable citizens. Patients with multiple myeloma (MM) have ...an increased risk of being infected with COVID-19 and developing a fatal course due to the related immunodeficiency. We investigated how Danish patients with MM reported their quality of life (QoL) pre-COVID and during COVID, in an ongoing longitudinal QoL survey. The responses given during the first and second wave of the COVID-19 pandemic were pooled, analyzed and compared to the same period the year before. We hypothesized that locking down the society would have caused deteriorated QoL and that patients living alone and those under the age of 65 would be particularly affected by the situation. Surprisingly, our study showed the opposite. Statistically significant and clinically relevant differences were primarily found during the first lock down and represented reduced fatigue, improved role functioning, decreased insomnia and improved physical health summaries in patients below 65 years of age. These results indicate that Danish patients with MM might have felt protected and safe by COVID restrictions. Otherwise, the questionaries used in QoL-MM survey may not have been able to capture the impact of the COVID-19 pandemic. Importantly, this indicates that QoL survey data obtained in clinical studies, in countries with highly developed health-care systems using standard questionnaires during the pandemic, allow room for interpretation without being adjusted for the impacts of the pandemic.
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