Bridging the Access Gap for Bispecific Antibodies in Community Oncology

As T-cell–engaging therapies redefine the treatment landscape for hematologic malignancies and increasingly move into solid tumor indications, community oncology practices face a critical choice: adapt to the operational complexities of these agents or risk limiting patient access to life-saving care. While bispecific antibodies offer remarkable efficacy, slow uptake in the community has often been driven by concerns regarding cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and the logistical demands of step-up dosing.

Ralph V. Boccia, MD, FACP, the founder of The Center for Cancer and Blood Disorders, clinical associate professor at MedStar Georgetown University Hospital, and medical director of the International Oncology Network Clinical Research Program, explained the mission of The Bispecifics Network. This new program launched on CancerNetwork® aims to educate clinicians on safe implementation and share the specific protocols—from patient kits to virtual oversight—that allow his clinic to manage these therapies in an outpatient setting. By addressing the barriers imposed by geographic distance and hospital reimbursement models, Boccia highlighted a path forward for making bispecifics a standard, accessible tool for oncologists nationwide.

CancerNetwork: What is the aim of The Bispecifics Network?

Boccia: Currently, the area of bispecifics, or T-cell–engaging therapy, is a very hot topic. It is one of the newest therapeutics that we can use today to treat patients with hematologic malignancies, and in the not-too-distant future, a lot of solid tumors as well. That said, bispecifics are used in small cell lung cancer. We do have some overlap with the hematologic malignancies, but there has been a slow uptake of these treatments because of the potential [adverse] effects that patients can get from them. There’s been a little bit of reluctance, especially out in the community, to begin treating patients with bispecifics, so it is our goal in The [Bispecifics] Network to help guide and teach the community how to implement these in a safe and effective fashion.

You are going to be working with a couple of different multidisciplinary leaders across the space for The Bispecifics Network. Why is it important to have this collaboration across those disciplines when speaking about the topic of bispecific antibodies?

The adverse event profile of bispecifics is a complicated one that involves not only cardiovascular-like [adverse] effects, but also neurologic [adverse] effects. If these adverse events become problematic and can’t be managed by just the treating physician, then you need this multidisciplinary team to help you through some of the toxic effects that can be seen.

The roundtable discussion is coming up. What do you hope your colleagues take away from the discussion and maybe subsequent in-depth interviews about the bispecific antibody space?

At the roundtable, we hope to be able to interact and understand why the implementation of bispecifics has been so slow. They are so incredibly effective; we are very interested in making sure that patients have access to these drugs. Access is more than just having it available; it’s having it available in a convenient way. Many physicians right now are prescribing them by sending them to academic centers and letting them at least do what’s called the step-up [dosing], which is the riskier period as you take the drug from the smallest dose and then ramp it up to the full therapeutic dose.

There are access problems because the label suggests that these patients at least be treated during the ramp-up in the hospitals. Most hospitals, because of DRGs [Diagnosis-Related Groups], will not admit patients for observation because all we admit them for is to observe them. Should they develop CRS? Should they develop ICANS? They’re there for us on watch. These are expensive drugs, so the hospitals, because of DRGs, are not interested in supplying the drug. Rather than treating the patient at the hospital, we’re merely admitting the patient for observation, and most hospitals will not allow that. If you can’t admit the patient and are uncomfortable doing it in clinic, then the patient just doesn’t get treated or has to be sent to some distant site, which is often problematic for the patients and their families. We hope at this roundtable to share experiences, look at what the impediments are, and hopefully work through those impediments.

What are some of the biggest operational hurdles in moving bispecific antibody administration from an inpatient setting to an outpatient community clinic?

There has to be an understanding of how to administer these drugs, how to pick appropriate patients for the drugs, and how to bill for the drugs. The system itself is somewhat complicated because once a patient is identified, you have to have a team that is prepared to deal with the potential [adverse] effects. Patients have to have a caregiver; you have to make sure that there is someone with them 24 hours a day during the first ramp-up period, which is often several weeks. You have to provide them with the tools and the understanding of how to monitor the patients, and you have to be able to provide oversight during the ramp-up that monitors these patients very closely.

In our clinic, the patient is administered the first dose of drug. The patient is on steroids to try to prevent some of the [adverse] effects. They’re in the clinic for about 6 hours on the first day. They come back the next day, where they’re seen and examined. They’re then seen at the end of the day virtually, and that occurs for the first week of each step-up dose. The patient is essentially seen twice a day. They have our cell phone numbers. We’re in contact with them so that we can visualize them in person or speak with their caregiver to make sure that all of the parameters that we are observing them for—blood pressure, oxygen level, mentation—are understood. If anything occurs, the treatment is implemented immediately.

With the current step-up dosing that is required for many bispecifics to mitigate CRS, how is your team managing the logistics of patient observation?

What we do is we provide them with a kit. The kit includes a blood pressure cuff, an oxygen sensor, and a thermometer. We provide them with a checklist of things to record so that we can discuss that checklist, either live if they come to the clinic, or during the virtual visits. We’re able to look for fever, hypoxia, blood pressure changes, and mental status changes, and therefore be prepared to intervene.

We give them prophylactic dexamethasone, and at the first sign of CRS, we then give them tocilizumab [Actemra], which is an IL-6 inhibitor. This immediately often corrects the fever, the hypoxia, and the hypotension. We’re prepared in the clinic to administer these medications if needed. We send them home with dexamethasone, and at the first sign of a fever, we have them take an additional dose. Often, that’s all it takes. If that isn’t sufficient and we were going to be administering the tocilizumab within a couple of hours, we could do that in the clinic, and we can often avoid the patient needing to go to the hospital.

For patients living far from major centers, how can you and your team help solve the rural or suburban access gap for these T-cell–redirecting therapies?

That can be a problem for some people. We insist that the patients be within an hour of our facility and the hospital. If it’s more than that, they’re not good candidates for bispecific or CAR T-cell therapy. Any of the T-cell–directing therapies would have to have those geographical issues solved. For some of these treatments, all it requires is a brief stay, sometimes close by, but truly, the patient should be within an hour of the facility. It usually isn’t so catastrophic that patients can’t be an hour away, but they probably shouldn’t be any further than an hour away because of the potential risks of CRS or ICANS.

Do you see a role for AI-driven risk stratification in your clinical trials, or even your practice, to help identify patients at a higher risk for severe neurotoxicity?

All those things are important. AI is here to stay, and AI is learning, so we’re beginning to use it more. We also do our own risk stratification for patients. Probably, the most important factor, whether it is bispecifics or the CAR Ts, is that the disease burden matters. You can look at disease burden in a variety of ways—physical exam, scans, blood work—depending on whether it’s a lymphoproliferative disorder like lymphoma or a plasma cell dyscrasia like multiple myeloma. There are different tools that you use to assess disease burden. Age, comorbidities, LDH, and scan results all help us risk stratify. AI can look and quickly pick out [patients] at the highest risk, and those probably should be treated at the hospital. The question is, how do you get them into the hospital?

Where is the future of bispecific antibody research headed?

It is probably to improve the efficacy, and we’re now going to be seeing tri-specific antibodies in a variety of different targets for different types of tumors. An enormous amount of research is going on now in solid tumors because we're now trying to bring more of them in. As I mentioned earlier, we do have a bispecific for small cell lung cancer, and we’ll soon have bispecifics for other solid tumors as well.