Integrating CAR T-Cell Therapy and Bispecific Antibodies Into Hematologic Malignancy Care: Anita D’Souza, MD

At a recent Institute for Value-Based Medicine® event, Anita D’Souza, MD, discussed the evolving role of chimeric antigen receptor (CAR) T-cell therapy and bispecific antibodies in hematologic malignancies, particularly multiple myeloma. D’Souza, associate chief of research in the Division of Hematology/Oncology and professor of medicine at Froedtert and the Medical College of Wisconsin Cancer Center in Milwaukee, noted that these therapies, initially reserved for later-line treatment, have demonstrated deep, durable responses even in heavily pretreated patients and are now being used earlier in the disease course, including in second- and third-line settings and in combination with established regimens.

D’Souza emphasized the need to optimize safety, expand access, and improve care delivery models. While CAR T remains largely confined to tertiary academic centers, bispecifics are increasingly administered in community settings, enhancing access for patients unable to travel or lacking caregiver support. Collaborative strategies between academic and community centers—such as shared-care models, telemedicine, and decentralized follow-up—are essential to broaden reach.

Innovations in care delivery, including outpatient administration of both CAR T and bispecifics, can improve cost-effectiveness by reducing hospitalization and resource utilization, provided adequate infrastructure exists for managing cytokine release syndrome (CRS) and other acute toxicities, according to D’Souza. Long-term supportive care focuses on preventing and managing cytopenias and infections through growth factors, antimicrobial prophylaxis, vaccination, and revaccination protocols.

Further, D’Souza explained that addressing disparities in access requires a multipronged approach, including ensuring every patient is evaluated at a tertiary center, leveraging telehealth for trial discussions, and decentralizing clinical trial participation. These steps, D’Souza concluded, are critical for realizing the full value of these transformative therapies in real-world practice.

This transcript was lightly edited; captions were auto-generated.

Transcript

What are the long-term value and cost-effectiveness considerations for integrating bispecific therapies and CAR T-cell therapy into the treatment landscape for hematologic malignancies?

That's a great question. Both bispecific and CAR T therapies have really become the mainstay for several hematologic malignancies. As a myeloma physician, I've seen how, in the last 5 years, these drugs have literally revolutionized how we treat patients. We have seen really excellent responses in patients who have relapsed up to multiple lines of treatment and who have been refractory to all our existing medications and still see a long-standing and deep response. We have seen how these drugs initially came on for use in the fourth, fifth, and beyond lines of treatment. But as we have seen how well they work, we are now learning how to use them earlier.

For example, CAR T therapies in multiple myeloma are now approved for use in the second line and third line, and with bispecifics, we are learning how to use them even in newly diagnosed patients. We are learning how to use them in combination with existing myeloma therapies. I think what we have learned right now is that these drugs have become a cornerstone of therapies for patients with myeloma, and now the challenge is, how do we use them earlier? How do we incorporate them in combinations with other drugs? And then, most importantly, how do we make these therapies even safer?

How can relationships between academic and community centers be optimized for patients undergoing CAR T-cell therapy or bispecific treatment to ensure continuity of care while improving the care delivery model?

Currently, these treatments are given at tertiary care centers. CAR T in particular is typically given at large academic centers. These are the typical transplant cancer centers where these clinical trials were done. But we also know that only a subset of myeloma patients have access to these centers. Similarly, the bispecifics also initially, we were using them in these larger centers, but now we have learned how to give these more safely in the community setting, and this has expanded access to patients who are not able to travel far to these academic sites, who might have other restrictions, and might not have caregiver support. The ability to give some of these treatments at community centers, I think, expands access to these therapies.

Then for CAR T, if you can't do them in these smaller programs, how do we collaborate with the larger centers? How do we implement strategies like telemedicine? How do we implement strategies where some of the care is done at the tertiary site, but we then do some of the follow-up, doing lab work, and doing the supportive care from the community side? So, I think those are all part of strategies of how we can work together with the community side.

What innovative care delivery models can be implemented to improve the cost-effectiveness of using CAR T-cell therapy and bispecific antibodies?

We do these treatments as outpatients now. The way these therapies have been approved by the FDA is that they have to be done in the inpatient setting, and that adds on days in hospital, it adds to the cost, [and] it adds to health care resource utilization. One of the strategies we have used to try to overcome this is by being able to do both CAR T as well as bispecifics in the outpatient setting.

Now, to do that, we have to have a strong infrastructure. We have to have the ability to manage CRS as an outpatient and the ability to give the chemotherapy and cell infusion as outpatient. But when these systems are in place, it certainly allows patients to be able to stay at home more and only be admitted to the hospital when the outpatient management fails or you need to up the level of care for patients.

What best practices can you share regarding supportive care after CAR T or bispecific therapy, and which toxicities—such as oral toxicities, infections, or cytopenias—should be prioritized in the community setting during follow-up?

With both CAR T and bispecifics, the initial toxicity is with [CRS and] ICANS. For those, we have algorithms and protocols in place [for] how to manage and at what grade we start treatment, and we have really good strategies in place such that we can manage most of that very rapidly.

What happens next, typically with both CAR T and bispecifics, is you'll often see cytopenia. And so, how do we manage the cytopenia? Use of growth factors when it's safe and the CRS as result, use of appropriate antimicrobials [as a prophylaxis to prevent] patients from getting infection. I think that is key, knowing that when there are cytopenias, you can hold the drug, and you can reduce the dose. Once patients have had a good response, you can increase the frequency of administering the bispecific, and I think all these strategies play a role.

I think infection mitigation is key, and this has to be implemented at the practice level so that all patients get that same level of care. Whether it is using [intravenous immunoglobulin] as primary prophylaxis [or] making sure you're vaccinating patients before you start giving bispecifics or CAR T. Often with CAR T, we revaccinate patients after several months, similar to what we do with stem cell transplants. I think those are very important.

[Also,] screening patients for hepatitis B and C before you administer these drugs, and then using anti-[blastomycosis] prophylaxis, [and] anti-[pneumocystis jirovecii pneumonia] prophylaxis. I think when you do all of these strategies, we see that we're able to control severe infections from happening, and we have seen in studies that it has led to survival benefits.

What steps can be taken to reduce disparities in access to CAR T and bispecifics, particularly among underserved populations or patients in rural settings?

In myeloma, we see several different types of disparities. It's a cancer of older adults, so the elderly patients sometimes are not able to travel far, and there's a disparity there. There are racial disparities in the sense that disease is more prevalent among certain racial groups, and we know that certain treatments have not been accessible at the same rate across racial groups.

Then finally, as you pointed out, rurality is also a disparity in the sense that distance and being able to get to academic programs and get to the centers where clinical trials are open might be an issue. I think this is where we have to be able to have every patient with myeloma be seen at least once at a tertiary care site, because I think once they are seen at a bigger center, once they know what the options out there are—whether transplant, CAR T, clinical trials—even if they don't do it at that time, they know that that's an option in the future.

How do we use telehealth to be able to discuss the option of trials with patients? I think that is something we need to learn. We need to learn and do better. [We need to] be able to decentralize clinical trials. I think all of these—there's not one solution that will fix disparities. I think we all have to work collaboratively, and it's a multi-pronged solution.