Analyzing First-line Therapy for Multiple Myeloma: Real-World Data Differs From Trials

This Q&A was originally featured in First Report Managed Care. For the full interview, please visit the First Report Managed Care.

A combination of bortezomib, lenalidomide, and dexamethasone (VRd) has been used as a first-line regimen for patients with multiple myeloma for years. However, the respective outcomes of a given regimen may not measure up in the clinic as compared with a clinical trial, says Dr Joshua Richter of Mount Sinai.

In this interview with First Report Managed Care, Dr Richter shares findings recently presented at the SOHO 2022 Annual Meeting. He discusses the effectiveness of VRd in a population of Medicare beneficiaries, as well as the impact of real-world evidence on clinical expectations.

What inspired you to conduct your research into patients receiving first-line VRd?

VRd has been a standard upfront therapy for myeloma for quite some time now—well over a decade. Interestingly enough, a lot of its utilization was based on phase 2 data.

Even though VRd has been used a very long time, the phase 3 SWOG S0777 study was published in 2017 initially, and then a more finalized version was published in 2020. That data was impressive, but there is a difference between what happens in clinical trials—when things are extremely well controlled and monitored and patients are properly selected—vs real-world data. I think the oncologic world is starting to embrace the impact of real-world data, not necessarily for defining how we treat but perhaps refining or optimizing how we treat.

We decided to look at patients who have been receiving VRd vs other regimens in the first-line setting. What does real-world data for VRd look like compared to clinical trials and other treatment options?

Can you walk us through the study, including your methods and any findings that stood out to you?

This was a retrospective study where we used Medicare research identifiable files from a CMS-like database. We looked at patients over the age of 18 and the first-line treatments they received between 2012 and 2018. Then we evaluated a number of clinical trial endpoints, including duration of therapy, time to next therapy, progression-free survival, and overall survival. Our study was subject to all the limitations of retrospective data analysis.

In total, our sample included 13,573 patients. That is quite a lot of patients. Unfortunately, there are a lot of people with myeloma—in the United States, the prevalence is probably around 32,000 to 33,000 new cases per year.

We found two main things. The first is if you received VRd, with or without transplant, you did better compared to pretty much any other induction regimen during that time, including bortezomib/dexamethasone and cyclophosphamide/bortezomib/dexamethasone (CyBorD). Second, interestingly, both in terms of progression-free survival and overall survival, the data are not quite as good as compared to studies that were more well controlled.

We need to be a little careful about quoting the data to our patients because there are some differences between the clinical trial cohort and non-trial cohort patients.

Thank you. How can clinicians or payers use these findings?

Our dataset ended in 2018. That provided us enough follow-up to study, because if we look at patients who received frontline therapy in 2022, we have no follow-up for them. We may know patients responded in 2022, but we have no data about how long that response lasts.

I think this establishes, especially for payers and clinicians, that VRd is still a standard. VRd is still associated with the best data we have, whether we choose to do or not do transplant. If you start off with another line of therapy, such as CyBorD, and you are concerned or want a better outcome, switching to VRd is certainly an option.

The difficulty here is upfront therapy has shifted a little bit. Now, anti-CD38 monoclonal antibodies are a major part of induction therapy, both with daratumumab/bortezomib/dexamethasone for patients who do not receive a transplant and daratumumab/VRd for those who do.

All these data are great, including the MAIA data with daratumumab/bortezomib/dexamethasone and GRIFFIN data with daratumumab/VRd. But I think our findings may force us to temper our expectations in the clinic because if the VRd data is not quite as good as that of the SWOG trial, the daratumumab/bortezomib/dexamethasone and daratumumab/VRd data in the clinic is probably not quite as good as that of MAIA and GRIFFIN.

Patients are doing better, the outcomes are amazing, but this gives us some pause to temper our expectations.

About Dr Richter

Joshua Richter, MD, is an associate professor of medicine, hematology, and oncology at the Tisch Cancer Institute, Icahn School of Medicine, at Mount Sinai. Dr Richter is also the director of myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai.