Original StudyThe Myeloma Landscape in Australia and New Zealand: The First 8 Years of the Myeloma and Related Diseases Registry (MRDR)
Introduction
Multiple myeloma (MM) is an incurable hematologic condition, the incidence of which increases with age.1 Despite this, real-world epidemiologic and survival data are scarce, with most available outcome data originating from highly selected patients in the context of a clinical trial—a population that may not be representative of the MM population encountered in routine clinical practice.2, 3, 4
Major changes have occurred in both the diagnosis and treatment of MM over the past 2 decades as a result of the introduction and increasing utilization of more sophisticated and informative diagnostic procedures, including cytogenetics/fluorescence in-situ hybridization (FISH), multiparameter flow cytometry, next-generation sequencing, and newer imaging modalities, and the development and availability of more effective treatment options. The introduction of high-dose melphalan conditioned autologous stem-cell transplantation (ASCT) in the 1990s in combination with newer pharmacotherapeutic options has resulted in reports of improved survival in MM—both progression-free survival (PFS) and overall survival (OS)—from a large number of prospective randomized trials.5 However, whether comparable outcomes are achievable in patients treated in different jurisdictions outside the context of clinical trials has yet to be determined.
Two highly effective classes of anti-MM therapeutics have been available for a number of years. First were protease inhibitors (initially bortezomib, followed by second-generation protease inhibitors including carfilzomib and ixazomib) and immunomodulatory agents (thalidomide, lenalidomide, and pomalidomide).6,7 More recently, therapeutics with alternative mechanisms of action, including monoclonal antibodies (daratumumab, isatuximab, elotuzumab), histone deacetylase inhibitors (panobinostat/vorinostat), and nuclear transport inhibitors (selinexor), have been evaluated and approved for use in MM.6,8 A diverse range of novel therapeutics, including immuno-oncologic agents such as antibody drug conjugates, bispecific T-cell engagers (and variations thereof), and genetically modified T cells, along with BH3 mimetics and CELMods (cereblon E3 ligase modulator), are being evaluated in clinical trials.9, 10, 11, 12 The efficacy of newer agents, as demonstrated in clinical trials, continues to inform frequently updated local and international clinical practice guidelines.13, 14, 15, 16, 17, 18, 19, 20, 21 However, evidence for the relevance and implementation of these guidelines and their outcomes in real-world clinical practice are scarce. Although real-world cancer survival data are available from cancer registries, significant inaccuracies are inherent. These registries are reliant on histologic diagnostic sample reporting, and consequently they have no link to clinical and radiologic findings that inform the clinicopathologic diagnosis of MM and its differentiation from other plasma cell disorders (PCD). Cancer registries also lack information about treatment, including supportive care, and the duration and tolerability/deliverability of treatment in a real-world context.
To date, studies of real-world populations have predominantly described small sample sets, particularly single-center experiences, resulting in limited data in relation to therapeutic efficacy and tolerability in routine practice without the significant resources often associated with clinical trial participation.22 In addition, critical differences between health systems—such as user-payer versus universal healthcare and lack of assessment of therapy combinations, including lenalidomide in the first line and many triplet therapy combinations—may mean that available data are not readily extrapolated across jurisdictions.23 This paucity of data provides a compelling rationale for large-scale clinical registries to provide data of real-world clinical practice.
The Myeloma and Related Diseases Registry (MRDR) is a large clinical registry that provides data for populations in Australia and New Zealand (ANZ), allowing detailed analysis of a wide range of clinical variables as well as specific research hypotheses. To our knowledge, this is the first time such a large data set has been available for the ANZ population. Establishing clinical practice patterns and outcome data for patients with MM as well as understanding contributors to variation in practice will enable physicians to offer the best standard of care to their patients and support the planning and provision of healthcare services.
Section snippets
Methods
The MRDR is a prospectively maintained clinical registry from ANZ. As of April 2020, a total of 44 sites (38 in Australia and 6 in New Zealand) had received ethics approval, with 38 active sites contributing patient data. The design, development, and implementation of the MRDR has been previously described.24
We reviewed all patients with diagnostic information registered on the MRDR between June 2012 and April 2020. Baseline characteristics, therapy, and outcome data were reviewed. Categorical
Results
From June 2012 to April 2020, a total of 3430 patients were registered onto the MRDR, including 2405 patients (70.1%) with a diagnosis of MM, 632 (18.4%) with monoclonal gammopathy of undetermined significance (MGUS), and 341 (9.9%) with smoldering MM (SMM). The remaining patients included solitary bone plasmacytoma (26, 0.8%), solitary extramedullary plasmacytoma (13, 0.4%), and plasma cell (PC) leukanemia (13, 0.4%) (Table 1).
Discussion
In this study, we report demographics, disease characteristics, patterns of treatment, and outcome data for patients with newly diagnosed (ND) MM registered on the MRDR. Of the 70.1% enrolled onto the MRDR with MM, the median age at diagnosis was 67 years. This is similar to several other reported real-world populations but younger than the historically accepted median diagnostic age for MM of 70 years.27, 28, 29, 30, 31, 32 Because the MRDR is yet to experience full binational population-based
Conclusion
To our knowledge, this is the first published literature from ANZ investigating real-world practice in relation to PCD, and in particular all NDMM. In a landscape where diagnostic, therapeutic, and outcome data almost exclusively originate from clinical trials, clinical registries provide a powerful tool to confirm the validity of implementing these trial-directed approaches into everyday clinical practice. Clinical registries such as the MRDR also provide insight into the uptake and adherence
Disclosure
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors; however, the ANZ MRDR has received funding from Amgen, Bristol-Myers Squibb, Celgene, Gilead, Janssen, Novartis, Sanofi, and Takeda. The authors have stated that they have no conflict of interest.
Acknowledgments
The authors thank the patients, hospitals, clinicians, and research staff at participating institutions for their support of the MRDR.
References (58)
- et al.
Proteasome inhibitors in multiple myeloma: 10 years later
Blood
(2012) - et al.
Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group
Blood
(2016) - et al.
International Myeloma Working Group updated criteria for the diagnosis of multiple myeloma
Lancet Oncol
(2014) - et al.
International Myeloma Working Group consensus approach to the treatment of multiple myeloma patients who are candidates for autologous stem cell transplantation
Blood
(2011) - et al.
Review of 1027 patients with newly diagnosed multiple myeloma
Mayo Clin Proc
(2003) - et al.
International Myeloma Working Group consensus recommendations on imaging in monoclonal plasma cell disorders
Lancet Oncol
(2019) - et al.
An international field study of the reliability and validity of a disease-specific questionnaire module (the QLQ-MY20) in assessing the quality of life of patients with multiple myeloma
Eur J Cancer
(2007) - et al.
Role of autologous stem-cell transplantation in multiple myeloma
Best Pract Res Clin Haematol
(2007) - et al.
Real-world outcomes of multiple myeloma: retrospective analysis of the Czech registry of monoclonal gammopathies
Clin Lymphoma Myeloma Leuk
(2018) - et al.
Recent trends in multiple myeloma incidence and survival by age, race, and ethnicity in the United States
Blood Adv
(2017)
Final analysis of survival outcomes in the phase 3 FIRST trial of up-front treatment for multiple myeloma
Blood
Cancer in Australia: An Overview in 2014
Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting
Blood Cancer J
Differences between unselected patients and participants in multiple myeloma clinical trials in US: a threat to external validity
Leuk Lymphoma
Analysis of common eligibility criteria of randomized controlled trials in newly diagnosed multiple myeloma patients and extrapolating outcomes
Clin Lymphoma Myeloma Leuk
Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients
Leukemia
Novel agents in the treatment of multiple myeloma: a review about the future
J Hematol Oncol
New insights into therapeutic targets in myeloma
Hematol Am Soc Hematol Educ Program
Investigational agents in immunotherapy: a new horizon for the treatment of multiple myeloma
Br J Haematol
A novel BCMA/CD3 bispecific T-cell engager for the treatment of multiple myeloma induces selective lysis in vitro and in vivo
Leukemia
Immunotherapy based on bispecific T-cell engager with hIgG1 Fc sequence as a new therapeutic strategy in multiple myeloma
Cancer Sci
Novel immunotherapies for multiple myeloma
Curr Hematol Malig Rep
Patient-centered practice in elderly myeloma patients: an overview and consensus from the European Myeloma Network (EMN)
Leukemia
European Myeloma Network recommendations on the evaluation and treatment of newly diagnosed patients with multiple myeloma
Haematologica
Prevention and management of adverse events of novel agents in multiple myeloma: a consensus of the European Myeloma Network
Leukemia
International Myeloma Working Group recommendations for global myeloma care
Leukemia
International Myeloma Working Group consensus statement for the management, treatment, and supportive care of patients with myeloma not eligible for standard autologous stem-cell transplantation
J Clin Oncol
Treatment of patients with multiple myeloma who are not eligible for stem cell transplantation: position statement of the Myeloma Foundation of Australia Medical and Scientific Advisory Group
Intern Med J
Treatment of patients with multiple myeloma who are eligible for stem cell transplantation: position statement of the Myeloma Foundation of Australia Medical and Scientific Advisory Group
Intern Med J
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Māori and Pacific Peoples With Multiple Myeloma in New Zealand are Younger and Have Inferior Survival Compared to Other Ethnicities: A Study From the Australian and New Zealand Myeloma and Related Diseases Registry (MRDR)
2022, Clinical Lymphoma, Myeloma and LeukemiaCitation Excerpt :This is a prospective cohort study of patients with newly diagnosed MM (NDMM) from 6 New Zealand hospital sites from the North and South Islands participating in the MRDR, recruited from September 2012 to April 2021. The MRDR, a prospective clinical quality registry of incident cases of MM, monoclonal gammopathy of undetermined significance (MGUS), and related diseases, has been previously described.8,9 Patients ≥ 18 years with NDMM, recruited from New Zealand sites on the MRDR, were included.
Multiple myeloma in general practice A guide to diagnosis and management
2023, Medicine Today