A peek behind the paper – Caitlin Costello on INSIGHT MM and real-world evidence

Take a look behind the scenes of a recent Future Oncology article, entitled ‘INSIGHT MM: a large, global, prospective, non interventional, real-world study of patients with multiple myeloma’ as we ask lead author Caitlin Costello from the University of California San Diego (CA, USA) about the importance of incorporating real-world evidence (RWE) into research as well as key findings from the INSIGHT MM study and how these findings could effect routine clinical practice.

In your opinion, how could real-world evidence (RWE) be used to help advance how we define the optimal therapeutic algorithm for different cancer types?

The patients I typically see in the real world can be very different from those treated in pivotal Phase III trials – they can be sicker, in a poorer physical condition and with more comorbidities, for example. The gold standard for determining the efficacy of a treatment or intervention is a randomized controlled trial, in which the treatment or intervention is studied under ideal circumstances, and while this is critical for demonstrating the efficacy of a new therapy, as we note in the paper, INSIGHT MM and other registry studies have shown that up to 40% of real-world patients aren’t eligible for clinical trials. These patients have poorer outcomes than patients who would be eligible for clinical trials. So, real-world evidence studies such as INSIGHT MM are really important for understanding the effectiveness of treatments, and whether they are tolerable in the broader population – not just in the selected population and controlled setting of clinical trials.

Real-world studies are also important for understanding what treatments patients are actually receiving and how these differ between countries and regions. Real-world data show us how clinicians in different regions are using the complex array of different treatment options to treat their patients and how these practices are affected by regional variations in guidelines and the treatments that are available. Another important piece of information that can be obtained from real-world studies is the practical burden associated with treatment administration and how this affects patients’ quality of life – this is not necessarily something that we capture in our clinical trials.

Please introduce our readers to the INSIGHT MM study.

The INSIGHT MM study ultimately aims to bridge the gap in the understanding of the efficacy of anti‑myeloma agents in clinical trials and their effectiveness in real-world settings.

 INSIGHT MM is including patients receiving anything from first -line to fourth-line therapy in order to understand patient and disease characteristics of real-world myeloma patients as they progress through the different stages of their disease.

We’re also investigating which regimens are most commonly prescribed for each line of therapy in different regions – and the most common sequences of treatments used by physicians. These data will help us gain an understanding of contemporary, real-world treatment patterns. In fact, the steering committee have already reported some interesting preliminary data from the study along these lines, including at ASH 2018 (Usmani et al) and EHA 2019 (Chari et al), showing how treatment can vary according to patient and disease characteristics as well as by region.

Among our other important aims are to increase our understanding of treatment feasibility and tolerability in the real world as well as patient outcomes. This will allow us to see how different agents and regimens benefit patients in various disease and treatment settings, see how the use of these treatments affects patients’ quality of life and healthcare resource utilization, and further our understanding of how real-world outcomes can differ from clinical trial findings.

What geographic differences in treatment options for MM has the INSIGHT MM study uncovered?

We’ve been looking at common treatment options across the 15 participating countries, as shown in Figure 2 in the paper, and analyzing the data within four geographic regions, namely North America (USA), Latin America, Europe, and Asia. We’ve seen some interesting findings already in our preliminary analyses, with very commonly used regimens in one region being hardly used in others (Boccadoro et al, EHA 2018; Usmani et al, ASH 2018; Chari et al, EHA 2019). There may be a number of explanations for these differences, including differences in drug availability, treatment guidelines, and prescribing practices around the world – our data to date clearly show that there isn’t a global uniform standard of care for newly diagnosed or relapsed/refractory multiple myeloma!

How do you hope INSIGHT MM might affect routine clinical practice?

We currently primarily use data from randomized clinical trials to guide our treatment decision-making for newly diagnosed and relapsed/refractory myeloma patients – and this will remain the ‘gold standard’. However, real-world data are becoming increasingly important to us, as they provide insight into how treatments perform outside the restricted clinical trial population. So, we hope that the findings from INSIGHT MM will ultimately contribute to improving patients’ care and outcomes by increasing clinicians’ understanding of treatment effectiveness and toxicity in the broader, real-world patient population. Our data from this study may help in the treatment decision-making process, with the goal of providing optimal treatment and outcomes for each patient.

Do you envisage the results of INSIGHT MM being able to help determine global standard-of-care treatment for patients with MM?

A recent analysis from INSIGHT MM (Chari et al, EHA 2019) has shown that no single global standard-of-care treatment for patients with MM currently exists and one is unlikely to evolve, given the complexity of the disease and the differences in treatment practices and availability around the world. However, we hope that our extensive dataset will help highlight optimal treatment options and sequences in different patient populations – and this will thereby potentially contribute to developments in regional standards of care, with the aim of improving patient outcomes. Additionally, real-world evidence is very important in decisions about reimbursement and approval of therapies in some countries, highlighting another valuable use for our dataset.

What are the next steps for the INSIGHT MM study?

Enrollment to INSIGHT MM is now complete – we’ve achieved our target enrollment of approximately 4200 patients, although we are yet to report data from the full population. The study still has a long time to run, as we’re following all patients prospectively for a minimum of 5 years. This duration of follow-up will provide a more mature dataset than we have at present, including long-term outcomes data. We plan to continue reporting interim data summaries and formal interim analyses as the study progresses, in order to disseminate the wealth of data that we are collecting. We are also planning and conducting collaborative, pooled data analyses with country-specific MM registries and other observational studies in order to explore a wide range of clinically relevant questions.

Which of the current ongoing non-interventional, observational, registry studies are you most interested in seeing the results of?

All of them! We’re seeing a number reports from various observational and registry studies in myeloma being published and presented – for example, other than the INSIGHT MM study, we’ve seen various data from Connect MM, CoMMpass, and PREAMBLE, and the Multiple Myeloma Research Foundation recently announced that it is incorporating the CoMMpass data into its new CureCloud™ initiative, which is aiming to collate huge amounts of genomic, immune and clinical data. There are also a number of individual country or region-based registries of patients.

All of these sources of real-world data will be valuable – because with a highly complex, heterogeneous disease like myeloma, the greater the volume of data, the better. This is the rationale of the collaborative approach that we are taking with INSIGHT MM – it is why we are planning to share our data and, more importantly, collate and conduct collaborative analyses with other observational study datasets and registries. We mention in the paper about collaborating with the Czech Registry of Monoclonal Gammopathies (Hajek et al, ASH 2018) and the Australian and New Zealand Myeloma and Related Diseases Registry, for example. We hope that such collaborations will allow us to explore a wide range of clinical questions in an even larger dataset – which should give our findings greater accuracy and make them more applicable and generalizable to the whole myeloma patient population.