Role of Real-World Evidence in the Evolving Treatment Landscape of Multiple Myeloma - Episode 2

A Multiple Myeloma Overview

Muhamed Baljević, MD, FACP, provides a background of multiple myeloma (MM) within the past five years and the main treatment options.

Ryan Haumschild, PharmD, MS, MBA: Hello, and welcome to this AJMC® Peer Exchange program titled “The Role of Real-world Evidence in the Evolving Treatment Landscape of Multiple Myeloma.” I’m Dr Ryan Haumschild, the director of pharmacy services at Emory Healthcare and the Winship Cancer Institute [in Atlanta, Georgia]. Joining me for this discussion are my esteemed colleagues Dr Muhamed Baljević, the director of plasma cell disorders research and amyloidosis programs at Vanderbilt University Medical Center [in Nashville, Tennessee]; Dr Roy Beveridge, a senior strategic adviser at Avalere Health [in Louisville, Kentucky]; Dr Joshua Richter, an associate professor of medicine at the Tisch Cancer Institute Division of Hematology and Medical Oncology, and the director of multiple myeloma at the Blavatnik Family Chelsea Medical Center at Mount Sinai [in New York, New York]; and Dr Jay Weaver, the chief pharmacy officer at Blue Cross Blue Shield of Kansas City [in Kansas City, Missouri]. Our panel of experts will explore the evolving multiple myeloma treatment landscape and discuss the current and future uses of real-world evidence in the treatment and management of multiple myeloma. Thank you for joining us. Let’s begin.

Let’s talk about the evolving multiple myeloma treatment landscape. There’s been a lot of development over the past 5 years in the way we treated multiple myeloma. Different agents, different combinations. The treatment landscape has evolved in its complexity, and I’d like us to provide a brief history and overview of some of the key treatment classes utilized in the management of multiple myeloma. Dr Baljević, let’s start with you. Can you break down some of those agents that are utilized and how they’re changing the landscape of treatment?

Muhamed Baljević, MD, FACP: Myeloma is an exciting area of hematologic malignancies. Several years ago, when I looked at the status of new regulatory approvals in oncology, myeloma trailed in only 1 cancer field in terms of the number of regulatory approvals by mechanism of action. It seems that the pace at which myeloma is continuing is following the rapid developments in immuno-oncology, especially immune-based treatments. What you alluded to is important. Proteasome inhibitors, immunomodulatory drugs or immunomodulatory agents, anti-CD38 targeting antibodies, and more recently the introduction of specialized immune-based therapies, such as CAR [chimeric antigen receptor] T cells and bispecific T-cell engagers or antibodies. It’s challenging to reshape how we think about myeloma and, more important, how we treat it at the beginning and also subsequently.

Proteasome inhibitors together with IMiDs [immunomodulatory imide drugs] and CD38 antibodies for a number of years have been the cornerstone of agents we use in the treatment of newly diagnosed multiple myeloma. We’ve known from several phase 2 studies that combining PIs [proteasome inhibitors] and IMiDs is beneficial and gives us deeper responses compared with PI or IMiD combinations with other agents—for example, alkylating agents. With the introduction of monoclonal antibodies such as daratumumab, and more recently with introduction of isatuximab, we’ve started moving the needle forward. Particularly over there, we have to point out the number of studies in newly diagnosed myeloma looking at the so-called quad combinations, where we combine PI, IMiD, and CD38 antibody with glucocorticoid vs a triplet, usually a PI, an IMiD, and a glucocorticoid.

We already have 2 quad regimens that are both FDA and EMA [European Medicines Agency] labeled: daratumumab, Velcade [bortezomib], thalidomide, and dexamethasone, as well as daratumumab, Velcade, melphalan, and prednisone. Both quads are available for use. They’re not as frequent in North America. Perhaps they’re more reflective of European practice patterns and some in Asia. But daratumumab–VTd [bortezomib, thalidomide, dexamethasone] is approved in newly diagnosed transplant-eligible patients, and daratumumab–VMP [bortezomib, melphalan, prednisolone] is approved in newly diagnosed transplant-ineligible patients. We already have some regimens available for clinical use in practice.

We’re awaiting results of some of the phase 3 trials to mature so we can learn whether we’re going to have labelings and approvals for some of the more modern combinations, such as Decadron [dexamethasone] in combination with daratumumab. Excitingly enough, in the last ASH [American Society of Hematology Annual Meeting], we saw powerful data from another quad combination, which was VRd [lenalidomide, bortezomib, dexamethasone] in combination within another CD38 monoclonal antibody, isatuximab. We saw a staggering rate of MRD [minimal residual disease]–negative responses even before the use of autologous transplant. It’s clear that these agents are cornerstones of effective approaches initially, and that very soon we’re going to learn if it’s better to start incorporating them earlier rather than later.

Finally, CAR T-cell therapies have revolutionized the way we look at relapsed/refractory myeloma. Many of us have a habit of saying that the 60% or 80% is the new 30%. I’m referring to is the overall response rate in highly relapsed/refractory patients. For example, looking historically at when bortezomib was developed and other proteasome inhibitors or daratumumab and CD38 monoclonal antibody activity was high 20% to low 30% in terms of how active they were in highly relapsed/refractory patients.

For CAR T cells, we already have 1 that’s FDA approved. It’s been about a year in March last year. bb2121, otherwise known as ABECMA [idecabtagene vicleucel], has been approved for the treatment of highly relapsed/refractory myeloma patients after at least 4 prior treatment lines and exposures to PI, IMiD, and a CD38 antibody. The overall response rate of this agent was about 80%. We’re also seeing the increasing amount of data on bispecifics showing staggering response rates. We have nearly 100% overall response rates from another CAR T-cell agent that’s scheduled to be reviewed by the FDA [very soon]. It’s truly unprecedented. The needle has been advancing our capability of managing these highly relapsed/refractory patients.

It’s important to note is that these agents are going to be studied earlier and earlier in the lines of treatment. Several studies are incorporating these agents as part of the first treatment or first line in patients with multiple myeloma. It’s fair to say that how we think of myeloma right now is not going to be how we’re going to be thinking about it within the next 5 years. How we thought about it 5 years ago is not the same as how we’re thinking about it right now.

Ryan Haumschild, PharmD, MS, MBA:Muhamed, you bring up some great points, and I like how you tied it together. I always think of this plasma cell disorder because it was 1 without a cure in mind, but now we want to treat as a chronic disease. We’re getting better in the way that we’re mismatching. Do we potentially use KRd [carfilzomib, lenalidomide, dexamethasone] in a more high-risk patient population? Are we using a quadruplet therapy in the standard-risk with transplant? Why do we look at translocation 11;14 difference? We’re seeing the research sometimes pace ahead of even guideline recommendations, and that’s what’s exciting. As you start to use combination therapy, you give patients that better opportunity especially if you move it closer in therapy.

This transcript has been edited for clarity.