Original Study
The Myeloma Landscape in Australia and New Zealand: The First 8 Years of the Myeloma and Related Diseases Registry (MRDR)

https://doi.org/10.1016/j.clml.2021.01.016Get rights and content

Abstract

Background

Real-world multiple myeloma (MM) data are scarce, with most data originating from clinical trials. The Myeloma and Related Diseases Registry (MRDR) is a prospective clinical-quality registry of newly diagnosed cases of plasma cell disorders established in 2012 and operating at 44 sites in Australia and New Zealand as of April 2020.

Methods

We reviewed all patients enrolled onto the MRDR between June 2012 and April 2020. Baseline characteristics, treatment, and outcome data were reviewed for MM patients with comparisons made by chi-square tests (categorical variables) and rank sum tests (continuous variables). Kaplan-Meier analysis was used to estimate progression-free survival and overall survival (OS).

Results

As of April 2020, a total of 2405 MM patients were enrolled (median age, 67 years, with 40% aged > 70 years). High-risk features were present in 13% to 31% of patients: fluorescence in-situ hybridization (FISH) ≥ 1 of t(4;14), t(14;16), or del(17p) 18%, International Staging System (ISS)-3 31%, and Revised ISS (R-ISS)-3 13%. Cytogenetic/FISH analyses were performed in 50% and 68% of patients, respectively, with an abnormal karyotype result in 34%. Bortezomib-containing therapy was the most common first-line therapy (79.3%, n = 1706). Patients not receiving bortezomib were older (median age, 76 vs 65 years, P < .001) with inferior performance status (Eastern Cooperative Oncology Group performance status ≥ 2, 41% vs 18%, P < .001). Median progression-free survival and OS were 30.8 and 65.8 months, respectively. Younger patients had superior OS (76.3 vs 46.7 months, P < .001, < 70 and ≥ 70 years, respectively). R-ISS score was available in 50.7% (n = 1220) of patients, and higher R-ISS was associated with inferior OS (R-ISS-1 vs R-ISS-2 vs R-ISS-3: not reached vs 68.1 months vs 33.2 months, respectively, P < .001).

Conclusion

Clinical registries provide a more complete picture of MM diagnosis and treatment, and highlight the challenges of adhering to best practices in a real-world context.

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.

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