In this final episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, Drs Usmani and Wasil, discuss plans for developing guidelines and policies to enhance management of bispecific T-cell engagers across various centers.

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Guidance and Future Plans

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 plans for developing guidelines and policies to enhance the management of bispecific T-cell engagers across various centers.

In terms of other guidance that you have for community physicians, is there anything you can add to what you have already mentioned?

 I think this is an evolving area, and having good two-way communication between the tertiary care centers and the community is extremely important. It’s quite possible that some of these therapies will move into early lines of treatment. As such, anything that we can do to help facilitate and improve the comfort level [regarding their use] is going to be very important. The majority of oncology care occurs in the community setting, so this is a critical learning phase period. The International Myeloma Working Group has come out with certain guidelines about how to manage these patients, but I think there is a follow-up paper or primer being developed that will be more community focused. And so, I’m sure there are going to be similar efforts as more solid oncology indications come about. That’s all I have to add, Tarun. This has been a really good discussion.

I also just wanted to let you know that this afternoon, we had our own discussion, and we were planning to form a group of 4 or 5 people to come up with some policies, procedures, and guidelines for our centers because we are spread all across Long Island, the Bronx, Brooklyn, Staten Island, and New York City. We want to come up with some group guidelines. Certainly, I will contact you because we’ll need your input, as well.

 Happy to do it, and it’s always a pleasure speaking with you.

Videos

In this final episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, experts discuss plans for developing guidelines and policies to enhance management of bispecific T-cell engagers across various centers.

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, Drs Usmani and Wasil discuss the need for continued evaluation of prophylactic treatments like tocilizumab (Actemra) and antimicrobial measures for bispecific T-cell engagers, noting logistical and financial challenges and the importance of collaboration with community centers.

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Prophylactic Measures

, Saad Z. Usmani, MD, MBA, FACP, FASCO, of Memorial Sloan Kettering Cancer Center, and Tarun Wasil, MBBS, FACP, of Northwell Medicine, discuss the need for continued evaluation of prophylactic treatments like tocilizumab (Actemra) and antimicrobial measures for bispecific T-cell engagers, noting logistical and financial challenges and the importance of collaboration with community centers.

That’s absolutely appropriate and I appreciate the fact that there are practices that actually have started to do outpatient treatments; that’s excellent, actually. There are even some data about prophylactic tocilizumab, and I think we’ll just have to see how those data emerge and how we can logistically do this because I think that there will be some insurance coverage concerns [that we will be met with] along the way, as well. The only other thing that I would add is that antimicrobial prophylaxis, or VZV prophylaxis with acyclovir or valacyclovir, is something that we do across the board for patients. Unless a patient has consistently low neutrophil counts and/or a history of bacterial infections, typically we don’t give fluoroquinolones but that is a consideration. Then, for people who become hypergammaglobulinemic, along with having respiratory infections, we would think about giving IVIG every 4 or 6 weeks or so.

Well said. I think we need to start with the prophylactic antibiotics and make a good connection with the community centers. Also, prophylactic use of tocilizumab, as you mentioned, is being studied. In one trial, which is in multiple myeloma with cevostamab, they did show that there was a marked decrease in the CRS rate after prophylactic tocilizumab. But again, it comes at the cost of financial toxicity, so we really need more guidance on that. Hopefully, we’ll get some data, maybe by ASH this year.

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, experts discuss the need for continued evaluation of prophylactic treatments like tocilizumab and antimicrobial measures for bispecific T-cell engagers.

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, Drs Usmani and Wasil emphasize the need for comprehensive patient education, effective communication, and specific safety protocols to manage patients receiving bispecific T-cell engagers.

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Management Strategies

, Saad Z. Usmani, MD, MBA, FACP, FASCO, of Memorial Sloan Kettering Cancer Center, and Tarun Wasil, MBBS, FACP, of Northwell Medicine, emphasize the need for comprehensive patient education, effective communication, and specific safety protocols to manage patients receiving bispecific T-cell engagers.

[Management] requires education of the patient, their family members, and the physician teams—not only in the community center but also in the hospital setting, as you said. Patients should be provided with a diary, with the blood pressure monitoring machine and pulse oximeter preferably, because they need to know when to call. They also should be provided with some specific [phone] numbers—not the general numbers for the services of various hospitals and centers—because there could be delays in getting help for those patients. In our practice, we do provide cell phone numbers to our patients [although] I understand that this is not possible for every physician. We also do some video calls on the weekdays. We can do video calls every couple of hours to make sure that patients are safe.

We have some study protocols now for myeloma as well as lymphoma, where we are starting some of these bispecific T-cell engagers [in the] outpatient [setting] and making sure that patients do well. In order to ascertain that, I think we need to educate a number of teams, as well as patients and their family members. If the patient is unable to really participate in this type of engagement, I think they must be admitted—especially the elderly patients—because safety is of the utmost concern, and we want to make sure that the patients stay safe.

 I completely agree with you. In our setup, we have a phone number that patients can call specifically for the bispecific therapies, and we actually have an outpatient physician beeper so that we can receive those calls and triage the patients. I think having that kind of a mechanism, especially as we get more patients who are receiving bispecific agents, is something that can be employed by community colleagues, as well—especially with a large group like yours, Tarun. I think that’s something that can be a shared responsibility.

Yeah, I think that’s important, and also giving them a dose of dexamethasone to keep at home. In case they actually have a fever and a slight decrease in blood pressure, they can at least take the dexamethasone while they are waiting for other help to arrive, or while they are on their way to the hospital. [In this way,] they can start treatment to some extent. 

I was talking to one of our practices in Tennessee, and they have some protocols. It seems like they have treated more than a few dozen patients [in the] outpatient [setting], and they give dexamethasone for a 3-day period in a [twice-daily] dosing, and aggressive hydration, which can help some of these patients avoid the hospitalizations to some extent. 

The other thing that we tried in a prior practice setting is doing the ramp-up dosing on a weekday, starting with Monday rather than on a Friday, because the weekend is always tricky. If the patients get sick, it is sometimes very hard for them to get help on a weekend. So those are some of the things that I think about when I start a patient on any bispecific on a protocol.

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, experts emphasize the need for comprehensive patient education, effective communication, and specific safety protocols to manage patients receiving bispecific T-cell engagers.

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, Drs Usmani and Wasil discuss the challenges and strategies in managing bispecific T-cell engagers in the realm of cancer, emphasizing the importance of community and tertiary care collaboration to handle unique toxicities like cytokine release syndrome (CRS) and the need for well-defined protocols to ensure patient safety and effective treatment.

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Awareness of AEs 

, Saad Z. Usmani, MD, MBA, FACP, FASCO, of Memorial Sloan Kettering Cancer Center, and Tarun Wasil, MBBS, FACP, of Northwell Medicine, discuss the challenges and strategies in managing bispecific T-cell engagers in the realm of cancer, emphasizing the importance of community and tertiary care collaboration to handle unique toxicities like cytokine release syndrome (CRS) and the need for well-defined protocols to ensure patient safety and effective treatment.

I think there’s one T-cell engager that’s already approved for small cell lung cancer and a lot more are being studied in prostate cancer, bladder cancer, and many others. As you said, [we need to be mindful of] the unique toxicity of CRS, immune effector cell–associated neurotoxicity syndrome, and [other] infections. Community physicians, and even the patients, get a little bit [nervous] about safety. Safety is the main concern here, and that’s why I think that collaboration between the tertiary care center and the community centers is of the utmost importance.

we are sending patients to you, at Memorial Sloan Kettering Cancer Center, or other tertiary care centers, to give the ramp-up dosing, which is the most important time when patients can develop CRS. It’s quite predictable; usually, most of the CRS happens after the first or second ramp-up dose, and sometimes, the third ramp-up dose. As such, that is the crucial period when patients get admitted. [Those at] tertiary care centers have a lot more experience and are the ones that can manage these effects. 

But I will ask you, what kind of policies and procedures can we put into place in the community setting so that we can take some of the workload [off of you and still] keep the patients safe? I think this is one of the areas that is going to expand very fast and by a lot. So, we need guidance in this field.

 I agree with you. I think this initial ramp-up period is very important; this is where one can see CRS, and many times, this is just a fever, and that fever can be managed with acetaminophen. If the fever occurs again, we have to think about how the patient needs to be brought in, managed closely, and be given tocilizumab [Actemra]. 

The initial approvals [of these agents] came with in-patient monitoring but what we are realizing now is that not every patient needs that. If you have patients who have good performance status; who live reasonably close by, so within half an hour; and have good social support, you can start them in the outpatient setting and provide them with guidance to call and come into the hospital so that they can receive tocilizumab [if they experience CRS]. This is where I think [it’s important to have] a good collaboration with the health care system that you are engaged with and making sure that their emergency room has the algorithm in place so that when these patients come in, they know exactly what to do. They can give them dexamethasone, they can give them tocilizumab, and monitor those patients. For the most part, [patients would undergo] observation for maybe only 23 hours, and then go home after that.

Once CRS happens, it typically doesn’t happen again. Recurrent CRS is very rare, and so, having those kinds of mechanisms in place will help. The patients you have to admit are the ones who are really sick, who have a high burden of disease; it’s better to monitor those patients on the in-person service side, and there, too, you have to apply the same algorithms. I think [this becomes] more of an education of the emergency room physicians and staff and making sure they have those algorithms in place, as well as the in-patient team that’s going to be taking care of patients. This can be created in a very nice manner, [by] looking at [and leveraging] bispecific SOPs. 

As we get more bispecifics, the patterns of CRS and infection risk will be different for different [agents]. But at least for the CRS management part, I think it will be straightforward; it can be applied to any product. When it comes to prophylactic antimicrobial coverage, so use of intravenous immunoglobulin potentially or the use of growth factors, it will depend on the product.

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, experts discuss the challenges and strategies in managing bispecific T-cell engagers in the realm of cancer, emphasizing the importance of community and tertiary care collaboration to handle unique AEs like CRS and the need for well-defined protocols.

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Awareness of AEs

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, Drs Usmani and Wasil 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, such as cytokine release syndrome and infection risks.

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

, 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.

 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.

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.

 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].

In this episode of OncChats: Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond, experts 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 toxicities.

Tarun Wasil, MBBS, FACP

Articles

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Guidance and Future Plans

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Prophylactic Measures

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Management Strategies

Optimizing the Use of Bispecific Antibodies in Myeloma and Beyond: Awareness of AEs

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