Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Overview

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, Saad Z. Usmani, MD, MBA, FACP, FASCO, of Memorial Sloan Kettering Cancer Center, and Tarun Wasil, MBBS, FACP, of Northwell Medicine, discuss bispecific T-cell engagers, highlighting their effectiveness in treating hematologic malignancies like multiple myeloma, their potential use in solid tumors, and the importance of managing unique adverse effects [AEs], such as cytokine release syndrome and infection risks.

Usmani: Hello, everyone. My name is Saad Z. Usmani, MD, MBA, FACP, FASCO. I’m a myeloma physician at the Memorial Sloan Kettering Cancer Center and serve as the chief of the service. It’s a pleasure to be here, and I am joined by my wonderful colleague, Tarun Wasil, MD, who will introduce himself.

Wasil: Yes, I’m Tarun Wasil, MD, and I’m a community oncologist. I take care of [patients with] all sorts of malignancies, but largely hematological malignancies, including multiple myeloma, diffuse large B-cell lymphoma, chronic leukemias, and myeloproliferative disorders. Today, it’s my pleasure to join my esteemed colleague and helper, Dr Usmani, who’s going to educate us on the very [exciting] topic of T-cell engagers. More and more patients are going to receive these medications, and we need to know how to get used to some of the AEs [associated with them,] as they are unique.

Usmani: Thank you so much, Tarun, for being here. I can start with some just general comments about bispecific T-cell engagers. Even though most of these therapies are currently in use for hematologic malignancies, there are many such therapies also being studied in clinical trials in solid tumors. I think, from a community practice perspective, it’s going to be very important to learn more about the data and just day-to-day management of these patients [who receive these agents].

The real concept [with] bispecific antibodies is to harness the patient’s T cells—or any immune cell can honestly be utilized or harnessed—to go after the tumor cells. One part of the bispecific antibody or the T-cell engager structure identifies the surface marker on the cancer cell and the other part recognizes a surface marker on the immune cell. Commonly, right now, we have T cells, so it’s CD3 on the T cells, and then, if it’s myeloma, we have BCMA, which has been utilized as the surface marker that bispecific [agents] can recognize. We also have GPRC5D, which is, another more selective marker for plasma cells. Then, we also have CD19-targeting bispecific antibodies for B-cell malignancies, and others are in development as well—even for leukemia and solid tumors.

Whenever we ask the T cells or immune cells to become more active or get engaged, they are going to secrete a lot of cytokines and give the body a similar kind of feeling as if the patient has an infection. So, [this may translate to] severe sepsis-like symptoms; or, I should say, SIRS-like symptoms can happen. Fevers, hypotension, [and] hypoxemia can occur in patients. So, it’s kind of that whole phenomenon encompassed in what we call cytokine release syndrome [CRS]. Unlike [what is seen with] CAR T-cell therapies, [with] bispecific antibody treatment, [CRS] is typically low grade; it’s typically grade 1 or 2 and can be very effectively managed with supportive care. We always have to check those patients for infections, etc., but the use of steroids, sometimes tocilizumab [Actemra], and fluids can help mitigate and manage that adverse effect [AE] for the most part—especially for the [patients with] myeloma. The other important AE that we always pay attention to is infection risk when it comes to BCMA-related treatments. I think whenever you ask these T cells to do their job, they’re going to get exhausted, and so, patients’ immune systems will be at a higher risk for infection.

I think those are some of the main things [to be aware of with these agents]. I’m happy to provide more details or feedback, but [I’ll start by saying] these are highly effective treatments for patients with myeloma, specifically in those who are triple-class refractory who have had 4 or more prior lines of treatment. [These patients] are seeing responses of 60% and 70%, which is quite remarkable, and these responses are long-lasting. The durability of response is 1.5 years, sometimes [over] 2 years for some of the products. [As such,] I think these bispecifics are likely going to impact not just the landscape of treatment for hematologic malignancies, but also solid [tumors].