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1.
J Cancer Surviv ; 18(1): 196-206, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36964294

RESUMO

PURPOSE: Our purpose was to examine the associations between the pillars of psychological flexibility (valued action, behavioural awareness, openness to experience) and aspects of quality of working life after a cancer. We examined how the pillars of psychological flexibility mediated the relationships between quality of working life and anxiety, depression, and overall life satisfaction. Examining psychological flexibility allows interventions to be targeted for cancer survivors and account for unique, individual needs. METHODS: In this cross-sectional study, 230 cancer survivors who were currently employed completed a questionnaire package that included demographic information and measures of physical health problems, satisfaction with life, quality of working life in cancer survivors, psychological flexibility, anxiety, and depression. RESULTS: The mediational analyses illustrated how specific pillars of psychological flexibility mediated the relationships between quality of working life and anxiety, depression, and overall satisfaction with life. Overall, psychological flexibility mediated the relationships between physical health and health-related work problems, quality of working life, and satisfaction with life. Further, the valued action pillar of psychological flexibility fully mediated the relationship between quality of working life and reported symptoms of depression and anxiety. CONCLUSIONS: Higher psychological flexibility was related to higher satisfaction with working life. Physical and psychological challenges during employment may be improved through interventions that improve psychological flexibility. Active engagement with activities aligned with personal values is related to more positive outcomes. IMPLICATIONS FOR CANCER SURVIVORS: The value of examining the pillars of psychological flexibility is that interventions can be targeted for this population, considering this population's unique needs.


Assuntos
Sobreviventes de Câncer , Neoplasias , Humanos , Estudos Transversais , Qualidade de Vida/psicologia , Sobreviventes/psicologia , Neoplasias/psicologia , Ansiedade/psicologia , Depressão/epidemiologia , Depressão/psicologia
2.
Health Psychol Behav Med ; 11(1): 2266220, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37849745

RESUMO

Background: The impact of cancer extends beyond treatment and evaluating the adverse psychological effects in survivors is important. We examined: (1) the relationship between diagnosis, relapse, and subjective well-being using a short and a holistic measure of well-being, including comparisons between our sample and established norms; (2) if reported physical symptoms were related to components of subjective well-being; and (3) if increased psychological flexibility predicted overall subjective well-being. Methods: In total, 316 survivors completed online questionnaires to assess cancer, physical health (Edmonton Symptom Assessment Scale-R; ESAS-R), subjective well-being (Comprehensive Inventory of Thriving; CIT; Satisfaction with Life Scale; SWLS) and psychological flexibility (Comprehensive Assessment of Acceptance and Commitment Therapy). Results: Relative to ESAS-R cut-points (Oldenmenger et al., 2013), participants reported only moderate levels of tiredness and slightly elevated drowsiness, depression, and anxiety; participants reported more problems with psychological health. SWLS scores were lower than published norms (M = 18.23, SD = 8.23) and a relapse was associated with the lowest SWLS scores (M = 16.95, SD = 7.72). There were differences in thriving between participants and age-matched norms (Su et al., 2014). Participants reported lower community involvement, respect, engagement with activities, skill mastery, sense of accomplishment, self-worth, self-efficacy, autonomy, purpose, optimism, subjective well-being, and positive emotions coupled with higher loneliness and negative emotions. In regression analysis, two components of psychological flexibility, Openness to Experience, t = 2.50, p < 0.13, ß = -0.18, and Valued Action, t = 7.08, p < 0.001, ß = -0.47, predicted 28.8% of the variability in total CIT scores, beyond the effects of demographic and disease characteristics and reported physical symptoms. Conclusion: Cancer is an isolating experience, with the adverse psychological effects that impact subjective well-being continuing after the cessation of physical symptoms. Specific components of psychological flexibility may explain some variability in thriving beyond disease characteristics and may inform psychological intervention after diagnosis.

3.
Blood Cancer J ; 13(1): 137, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37669949

RESUMO

Autologous stem cell transplant (ASCT) remains an important option for eligible multiple myeloma (MM) patients as part of initial therapy. Using the Canadian Myeloma Research Group (CMRG) national database, we examined the details and outcomes of ASCT performed as first-line therapy in eligible Canadian MM patients between 2007 to 2021. We included 3821 patients with 72% receiving CyBorD induction and 2061 patients receiving maintenance, consisting of lenalidomide +/- steroids in 78.3%. The median PFS and OS for patients given a single ASCT were 35.4 and 126 months. Those receiving a second induction regimen had significantly inferior outcomes, although when maintenance was used, results were comparable regardless of the number of induction regimens administered (median PFS 55.3 vs 51.1 months [p = 0.11]; median OS 158.6 vs not yet reached [p = 0.13]). Consolidation patients had a longer median PFS (55.3 vs 34.4 months [p = 0.001]), but no significant gain in median OS (p = 0.065). Patients who received lenalidomide-based maintenance experienced a median PFS of 53.7 months and OS of 159 months. In the multivariable analysis, use of any type of maintenance therapy vs no maintenance was associated with a lower risk of progression (HR 0.52 (95% CI 0.47-0.57)) and death (HR 0.58 (95% CI 0.51-0.67)). This real-world study demonstrates that, overall, first-line treatment sequence in transplant-eligible patients produces a median OS of ≥10 years. It also highlights the contribution of post-ASCT maintenance, particularly lenalidomide given until progression.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Transplante Autólogo , Lenalidomida , Canadá , Transplante de Células-Tronco
5.
Res Involv Engagem ; 9(1): 60, 2023 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-37516883

RESUMO

BACKGROUND: Over the last decade there has been considerable research into the treatment, management, and quality of life of people living with multiple myeloma. However, there has been limited investigation into topics deemed important to patients and caregivers within this community. We conducted a James Lind Alliance Priority Setting Partnership to establish the 'Top 10 Priorities for Myeloma Research', informed by patient and public partners. METHODS: A research team and steering group were established in 2019 to conduct the myeloma priority setting partnership. Steering group members included patients, caregivers, and healthcare providers who advised the research team and oversaw the scope of the project, grounded on their lived experience. Following the James Lind Alliance guidelines for identification and ranking of research questions, we used surveys and a virtual workshop to collect and prioritize questions posed by myeloma patients, caregivers, and healthcare providers across Canada. RESULTS: The Top 10 list of priorities for myeloma research was finalized at the consensus-building workshop and encompassed questions related to diagnosis, treatment, management, and living well with myeloma. A final participant evaluation survey elicited a positive response. INTERPRETATION: The myeloma priority setting partnership identified the research priorities of people living with myeloma, caregivers, and healthcare providers to inform clinical research on this disease going forward. This project underscores the importance of patient and public engagement in the identification of research questions, highlighting the concerns of people affected by myeloma to ultimately improve the lives of people living with this disease.


Research on multiple myeloma, a rare blood cancer, rarely focuses on topics that are personally important to people living with myeloma, their caregivers, and their healthcare providers. The purpose of this study was to complete a priority setting partnership, following guidelines from the James Lind Alliance, to identify unanswered research questions from people directly affected by myeloma. The project was guided by a steering group of people living with myeloma, their caregivers, and healthcare providers who informed all stages of this process including two questionnaires to collect and rank questions and a priority setting workshop. The workshop brought together representatives from each group to form the final 'Top 10 Priorities for Myeloma Research', which included questions related to diagnosis, treatment, management, and living well with myeloma. This process allowed us to identify the research priorities of the myeloma community and highlighted the importance of including patients and the public as team members in the research process. We encourage other myeloma researchers to do the same to ensure research is meaningful and relevant to the communities who rely on it.

6.
Blood Cancer J ; 13(1): 111, 2023 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-37474492

RESUMO

While most patients diagnosed with multiple myeloma (MM) receive initial therapy, reported attrition rates are high. Understanding attrition rates and characteristics of patients not receiving subsequent therapy is useful for MM stakeholders. We performed an analysis of attrition rates in a large disease-specific database of patients with newly diagnosed MM who received at least one line of therapy between Jan 1/10-Dec 31/20. Attrition was defined as failure to receive a subsequent line of therapy despite progression of MM or due to death. A total of 5548 patients were identified, 3111 autologous stem cell transplant (ASCT) patients and 2437 non-ASCT. In the ASCT cohort, the attrition rate was 7% after line 1, 12% after line 2, and 23% after line 3. In non-ASCT patients, the attrition rate was 19% after line 1, 26% after line 2, and 40% after line 3. Death was the dominant contributor to attrition across all cohorts, with a minority of patients alive with progressive disease in the absence of further therapy at each line. Multivariable analysis identified older age, shorter time to progression, and inferior response as independent risk factors for attrition. Our data show that attrition rates increase with each line of therapy and are higher in non-ASCT patients but are appreciably lower than previously reported. This study supports a revision of the previous definition of attrition, demonstrating that most patients who do not receive subsequent therapy are either continuing their current therapy and/or are in remission off-treatment rather than being irreversibly lost to attrition.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/epidemiologia , Mieloma Múltiplo/terapia , Canadá , Transplante de Células-Tronco , Transplante Autólogo , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
7.
Cancer Med ; 12(4): 4357-4362, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36161712

RESUMO

Using the Canadian Myeloma Research Group Database, a retrospective study of 167 newly diagnosed, transplant-ineligible patients with multiple myeloma (MM) that received lenalidomide-dexamethasone as front-line treatment was conducted to understand the impact of lenalidomide dosing. Starting dose modifications were common, 42% of patients started on lenalidomide <25 mg with normal renal function. During treatment course, 35% of patients required further dose reduction. Dose reductions in the first year did not have an impact on progression free survival or overall survival. Further studies need to be conducted to understand the impact of dosing strategies of anti-MM agents in the real world.


Assuntos
Mieloma Múltiplo , Humanos , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Lenalidomida , Estudos Retrospectivos , Bortezomib , Dexametasona , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Canadá/epidemiologia , Resultado do Tratamento
8.
EJHaem ; 3(4): 1252-1261, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36467802

RESUMO

Carfilzomib is an active and commonly used treatment in patients with multiple myeloma (MM). Using the Canadian Myeloma Research Group Database, we performed a retrospective observational study of patients treated with carfilzomib for relapse of MM in a real-world setting in Canada between years 2007 and 2020. A total of 445 patients were included in this study: the doublet (Kd/p, n = 218) and triplets (KCd, n = 88; KRd, n = 99; KPd/p, n = 40). One hundred and twenty-two (27%) received carfilzomib-based treatment in line 2, 133 (30%) in line 3, 90 (20%) in line 4, and 100 (23%) in line 5 or higher. Carfilzomib was dosed weekly in 40% of patients and twice weekly in 60%. The overall response rate of the entire cohort was 57.7%, with 33.6% of patients achieving very good partial response or better. Median progression-free survival for the overall cohort was 6.3 months with overall survival 19.7 months. This study provides a benchmark for carfilzomib-based regimens in the real world, demonstrating that these regimens are effective in treating patients with relapsed MM.

9.
Blood Cancer J ; 12(6): 98, 2022 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-35768410

RESUMO

A wide variety of new therapeutic options for Multiple Myeloma (MM) have recently become available, extending progression-free and overall survival for patients in meaningful ways. However, these treatments are not curative, and patients eventually relapse, necessitating decisions on the appropriate choice of treatment(s) for the next phase of the disease. Additionally, an important subset of MM patients will prove to be refractory to the majority of the available treatments, requiring selection of effective therapies from the remaining options. Immunomodulatory agents (IMiDs), proteasome inhibitors, monoclonal antibodies, and alkylating agents are the major classes of MM therapies, with several options in each class. Patients who are refractory to one agent in a class may be responsive to a related compound or to a drug from a different class. However, rules for selection of alternative treatments in these situations are somewhat empirical and later phase clinical trials to inform those choices are ongoing. To address these issues the NCI Multiple Myeloma Steering Committee formed a relapsed/refractory working group to review optimal treatment choices, timing, and sequencing and provide recommendations. Additional issues considered include the role of salvage autologous stem cell transplantation, risk stratification, targeted approaches for genetic subsets of MM, appropriate clinical trial endpoints, and promising investigational agents. This report summarizes the deliberations of the working group and suggests potential avenues of research to improve the precision, timing, and durability of treatments for Myeloma.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Consenso , Humanos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia , Transplante Autólogo
10.
JACC CardioOncol ; 4(1): 85-94, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35492824

RESUMO

Background: Patients with cancer and cancer survivors are at increased risk for incident heart failure, but there are conflicting data on the long-term risk for other cardiovascular events and how such risk may vary by cancer site. Objectives: The aim of this study was to determine the impact of a new cancer diagnosis on the risk for fatal and nonfatal cardiovascular events. Methods: Using administrative health care databases, a population-based retrospective cohort study was conducted among 4,519,243 adults residing in Alberta, Canada, from April 2007 to December 2018. Participants with new cancer diagnoses during the study period were compared with those without cancer with respect to risk for subsequent cardiovascular events (cardiovascular mortality, myocardial infarction, stroke, heart failure, and pulmonary embolism) using time-to-event survival models after adjusting for sociodemographic data and comorbidities. Results: A total of 224,016 participants with new cancer diagnoses were identified, as well as 73,360 cardiovascular deaths and 470,481 nonfatal cardiovascular events during a median follow-up period of 11.8 years. After adjustment, participants with cancer had HRs of 1.33 (95% CI: 1.29-1.37) for cardiovascular mortality, 1.01 (95% CI: 0.97-1.05) for myocardial infarction, 1.44 (95% CI: 1.41-1.47) for stroke, 1.62 (95% CI: 1.59-1.65) for heart failure, and 3.43 (95% CI: 3.37-3.50) for pulmonary embolism, compared with participants without cancer. Cardiovascular risk was highest for patients with genitourinary, gastrointestinal, thoracic, nervous system and hematologic malignancies. Conclusions: A new cancer diagnosis is independently associated with a significantly increased risk for cardiovascular death and nonfatal morbidity regardless of cancer site. These findings highlight the need for a collaborative approach to health care for patients with cancer and cancer survivors.

11.
Clin Lymphoma Myeloma Leuk ; 22(8): 608-617, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35379589

RESUMO

BACKGROUND: Considerable progress has been made in therapeutic options for multiple myeloma (MM). Understanding the current landscape of MM treatment options and associated outcomes in the real world is important in providing key insights into clinical and knowledge gaps which could be targeted for further optimization. METHODS: The Canadian Myeloma Research Group Database (CMRG-DB) is a prospectively maintained disease-specific database with >7000 patients. The objective of this study was to describe the trends in the treatment landscape and outcomes including early mortality, time to next treatment, and overall survival (OS) in each line of treatment stratified by autologous stem cell transplant (ASCT) receipt among newly-diagnosed MM patients in Canada between 2007 and 2018. RESULTS: A total of 5154 patients were identified among which 3030 patients (58.8%) received an upfront ASCT and 2124 (41.2%) did not. At diagnosis, the median age was 64 years and 58.6% were males. Bortezomib and lenalidomide were most frequently used (>50%) in first and second-line treatment respectively among both the ASCT and non-ASCT cohort. The median OS was 122.0 months (95% Cl 115.0-135.0 months) and 54.3 months (95% CI 50.8-58.8 months) for the ASCT and non-ASCT cohort respectively with an incremental decrease in OS in each subsequent line of treatment. CONCLUSION: We present the largest study to date in the Canadian landscape showing the characteristics, therapy usage, and outcomes among MM patients. This information will be critical in benchmarking current outcomes and provide key insight into areas of unmet needs and gaps for improvement of MM patients nationally.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bortezomib , Canadá/epidemiologia , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lenalidomida/uso terapêutico , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/terapia , Estudos Retrospectivos , Transplante Autólogo
12.
Br J Haematol ; 198(1): 93-102, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35383886

RESUMO

Daratumumab (dara) has significantly altered the therapeutic landscape of multiple myeloma (MM), especially in the relapsed setting. This study aimed to evaluate the outcomes of dara-containing regimens in the Canadian real-world setting among relapsed and refractory MM available within the national Canadian Myeloma Research Group Database (CMRG-DB). A total of 583 MM patients who received dara-based therapy in second-line or later treatment were included. After a median follow-up of 17.5 months, the median progression-free survival (PFS) and overall survival (OS) for the entire cohort were 13.1 and 32.9 months, respectively. The median PFS and OS were 23.5 and 49.1 months in second-line treatment and decreased to 12.8 and 43.0 months in third-line and 7.0 and 20.5 months in fourth-line treatment respectively. Dara in monotherapy with or without corticosteroids after a median of four prior lines of therapy resulted in a median PFS of 3.9 months and a median OS of 17.1 months. The addition of bortezomib, lenalidomide or pomalidomide to dara resulted in an improved median PFS and OS of 8.3 and 26.2 months; 26.8 and 43.0 months; and 9.7 and 31.4 months respectively. These retrospective data from the CMRG-DB suggest that outcomes are superior when dara is used in combination and in earlier lines of treatment.


Assuntos
Mieloma Múltiplo , Anticorpos Monoclonais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Canadá/epidemiologia , Estudos de Coortes , Dexametasona , Humanos , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos
13.
Front Oncol ; 12: 826342, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35251992

RESUMO

BACKGROUND: Daratumumab, a monoclonal antibody directed against CD38 is a recent class of drugs introduced into the multiple myeloma therapeutic landscape. While clinical trial data have shown a remarkable impact on outcomes, the efficacy of daratumumab combination therapies in specific clinically relevant subgroups including among patients refractory to lenalidomide maintenance remains unknown. METHODS: In this study, retrospective data were reviewed from the Canadian Myeloma Research Group and the German Munster Myeloma databases to identify patients that received daratumumab in combination with pomalidomide (DPd), lenalidomide (DRd), and bortezomib (DVd) in a population that had relapsed on lenalidomide maintenance postautologous stem cell transplant. The primary aim of the study was to look at outcomes of these patients in different daratumumab combinations. RESULTS: A total of 73 patients were identified. The median age of the patients at the time of daratumumab initiation was 60 (38-72) and 64.4% (n = 47) were men. In the selected cohort, 43.8% (n = 32) were treated with DRd, 31.5% (n = 23) with DVd, and 24.7% (n = 18) with DPd regimen. The median progression-free survival (PFS) of the entire cohort was 15.8 months (95% CI, 12.9-37.1 months). The median PFS of the individual regimens was as follows: DPd 18.9 months (95% CI, 13.7-not reached), DRd 21.7 months (95% CI, 11.6-not reached), and DVd 12.9 months (95% CI, 3.1-not reached). CONCLUSIONS: Daratumumab-containing therapies are effective regimens in patients progressing on lenalidomide maintenance. Additional studies are required to decide the optimal regimen post-lenalidomide maintenance.

14.
Mol Ther Oncolytics ; 24: 695-706, 2022 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-35284625

RESUMO

Cancer cell energy metabolism plays an important role in dictating the efficacy of oncolysis by oncolytic viruses. To understand the role of multiple myeloma metabolism in reovirus oncolysis, we performed semi-targeted mass spectrometry-based metabolomics on 12 multiple myeloma cell lines and revealed a negative correlation between NAD+ levels and susceptibility to oncolysis. Likewise, a negative correlation was observed between the activity of the rate-limiting NAD+ synthesis enzyme NAMPT and oncolysis. Indeed, depletion of NAD+ levels by pharmacological inhibition of NAMPT using FK866 sensitized several myeloma cell lines to reovirus-induced killing. The myelomas that were most sensitive to this combination therapy expressed a functional p53 and had a metabolic and transcriptomic profile favoring mitochondrial metabolism over glycolysis, with the highest synergistic effect in KMS12 cells. Mechanistically, U-13C-labeled glucose flux, extracellular flux analysis, multiplex proteomics, and cell death assays revealed that the reovirus + FK866 combination caused mitochondrial dysfunction and energy depletion, leading to enhanced autophagic cell death in KMS12 cells. Finally, the combination of reovirus and NAD+ depletion achieved greater antitumor effects in KMS12 tumors in vivo and patient-derived CD138+ multiple myeloma cells. These findings identify NAD+ depletion as a potential combinatorial strategy to enhance the efficacy of oncolytic virus-based therapies in multiple myeloma.

15.
Curr Oncol ; 29(3): 1575-1582, 2022 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-35323332

RESUMO

The treatment of multiple myeloma has dramatically improved due to the availability of novel therapies that are highly effective and are quickly moving into first-line therapy. The Canadian Agency for Drugs and Technologies in Health (CADTH) recently recommended that patients who receive daratumumab should only be eligible to receive either carfilzomib or pomalidomide but not both, for relapsed MM. In order to assess the efficacy of these two agents in the relapsed setting, we utilized our national myeloma database. A total of 121 patients were reviewed, 49 patients received CAR- before POM-based (CAR-POM), and 73 patients received POM- before CAR-based (POM-CAR) therapy. In the groups selected, the median PFS was 4.93 months (95% CI, 2.76-7.07) and 5.36 months (95% CI, 3.75-6.94) for CAR-POM and POM-CAR, respectively. The median OS for patients treated with CAR-POM was 11.01 months (95% CI, 4.50-19.13), and for patients treated with POM-CAR the median OS was 10.98 months (95% CI, 8.98-19.17). In this real-world observational study, we demonstrated that both CAR- and POM-based therapies, irrespective of the order in which they were used, were effective treatment options for patients with advanced relapsed MM.


Assuntos
Mieloma Múltiplo , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Canadá , Dexametasona/uso terapêutico , Humanos , Mieloma Múltiplo/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Oligopeptídeos , Talidomida/análogos & derivados
16.
Lancet Haematol ; 9(2): e143-e161, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35114152

RESUMO

Infection remains the leading cause of morbidity and mortality in patients with multiple myeloma because of the cumulative effect of disease, treatment, and host-related factors. Given that infectious risk is cumulative through the course of the disease, preventing infections is paramount. Optimal preventive strategies include vaccination against common pathogens, antimicrobial prophylaxis, infection control measures, and immunoglobulin replacement in a small subset of patients; however, there are no universally accepted guidelines for infection prevention. This Review provides a consensus statement from a panel of 36 experts with global representation, which was convened by The International Myeloma Society to review existing literature and current guidelines, address issues associated with the risk of infection and prevention of infectious complications in multiple myeloma in the context of emerging therapies, and offer recommendations for preventing these complications.


Assuntos
Infecções , Mieloma Múltiplo , Consenso , Humanos , Infecções/complicações , Mieloma Múltiplo/complicações , Mieloma Múltiplo/tratamento farmacológico
18.
Curr Oncol ; 28(5): 4174-4183, 2021 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-34677272

RESUMO

The Canadian Real-world Evidence for Value in Cancer Drugs (CanREValue) Collaboration was established to develop a framework for generating and using real-world evidence (RWE) to inform the reassessment of cancer drugs following initial health technology assessment (HTA). The Reassessment and Uptake Working Group (RWG) is one of the five established CanREValue Working Groups. The RWG aims to develop considerations for incorporating RWE for HTA reassessment and strategies for using RWE to reassess drug funding decisions. Between February 2018 and December 2019, the RWG attended four teleconferences (with follow-up surveys) and two in-person meetings to discuss recommendations for the development of a reassessment process and potential barriers and facilitators. Modified Delphi methods were used to gather input. A draft report of recommendations (to December 2018) was shared for public consultation (December 2019 to January 2020). Initial considerations for developing a reassessment process were proposed. Specifically, reassessment can be initiated by diverse stakeholders, including decision makers from public drug plans or industry stakeholders. The reassessment process should be modelled after existing deliberation and recommendation frameworks used by HTA agencies. Proposed reassessment outcome categories include maintaining status quo, revisiting funding criteria, renegotiating price, or disinvesting. Overall, these initial considerations will serve as the basis for future advancements by the Collaboration.


Assuntos
Antineoplásicos , Neoplasias , Canadá , Humanos , Neoplasias/tratamento farmacológico , Inquéritos e Questionários , Avaliação da Tecnologia Biomédica
19.
Eur J Haematol ; 107(4): 416-427, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34129703

RESUMO

Lenalidomide is an important component of initial therapy in newly diagnosed multiple myeloma, either as maintenance therapy post-autologous stem cell transplantation (ASCT) or as first-line therapy with dexamethasone for patients' ineligible for ASCT (non-ASCT). This retrospective study investigated treatment patterns and outcomes for ASCT-eligible and -ineligible patients who relapsed after lenalidomide as part of first-line therapy, based on data from the Canadian Myeloma Research Group Database for patients treated between January 2007 and April 2019. Among 256 patients who progressed on lenalidomide maintenance therapy, 28.5% received further immunomodulatory derivative-based (IMiD-based) therapy (lenalidomide/pomalidomide) without a proteasome inhibitor (PI) (bortezomib/carfilzomib/ixazomib), 26.2% received PI-based therapy without an IMiD, 19.5% received both an IMiD plus PI, 13.5% received daratumumab-based regimens, and 12.1% underwent salvage ASCT. Median progression-free survival (PFS) was longest for daratumumab-based therapy (22.7 months) and salvage ASCT (23.4 months) and ranged from 6.6 to 7.3 months for the other treatments (P < .0001). Median overall survival (OS) was also longest for daratumumab and salvage ASCT. A total of 87 non-ASCT patients received subsequent therapy, with 66.7% receiving bortezomib-based therapy and 13.8% receiving other PI-based therapy. Median PFS was 15.4 and 24.8 months for bortezomib-based and other PI-based therapy, respectively (P = .404). During most of the study period, daratumumab was not funded; in this setting, switching to a different therapeutic class following relapse on lenalidomide produced the longest remissions for non-ASCT patients. Further prospective studies are warranted to determine optimum treatment following relapse on lenalidomide, especially in the light of increased access to daratumumab.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Transplante de Células-Tronco Hematopoéticas , Lenalidomida/uso terapêutico , Mieloma Múltiplo/terapia , Adulto , Idoso , Anticorpos Monoclonais/uso terapêutico , Compostos de Boro/uso terapêutico , Bortezomib/uso terapêutico , Canadá , Dexametasona/uso terapêutico , Feminino , Glicina/análogos & derivados , Glicina/uso terapêutico , Humanos , Quimioterapia de Manutenção , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/mortalidade , Mieloma Múltiplo/patologia , Oligopeptídeos/uso terapêutico , Recidiva , Estudos Retrospectivos , Terapia de Salvação , Análise de Sobrevida , Talidomida/análogos & derivados , Talidomida/uso terapêutico , Transplante Autólogo
20.
Eur J Haematol ; 106(5): 673-681, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33539037

RESUMO

OBJECTIVES: To understand the impact of therapy sequencing on progression-free (PFS) and overall survival (OS) for the treatment of multiple myeloma (MM). The use of daily, low-dose, lenalidomide maintenance (LM) has raised concern for fostering resistance, preventing its use in the relapsed setting. METHODS: We conducted a retrospective analysis of survival outcomes from the Canadian Myeloma Research Group Database. Patients were grouped based on receipt of LM after autologous stem cell transplant and receipt of lenalidomide in second-line therapy, 575 patients were included. RESULTS: Patients treated with LM had statistically similar 2nd PFS when re-exposed to lenalidomide in second-line therapy compared to those receiving non-lenalidomide-containing regimens (10.2 vs 14.0 months, P =.53). This cohort also had the longest 2nd OS, 18 months longer than patients treated with LM who did not receive lenalidomide at relapse (55.3 vs 37 months, P =.004). Patients treated with LM also demonstrated deeper responses to second-line therapy than their non-LM counterparts. CONCLUSION: Our data suggest that patients progressing on LM who receive lenalidomide-containing therapy at first relapse have comparable 2nd PFS and better 2nd OS compared to non-lenalidomide-containing second-line regimens. Identification of patients mostly likely to benefit from further lenalidomide-containing therapy is paramount.


Assuntos
Lenalidomida/uso terapêutico , Mieloma Múltiplo/terapia , Cuidados Pré-Operatórios , Canadá , Gerenciamento Clínico , Transplante de Células-Tronco Hematopoéticas , Humanos , Lenalidomida/administração & dosagem , Quimioterapia de Manutenção , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/mortalidade , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
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