Impact of COVID-19 on CAR T-Cell Therapy for R/R DLBCL

Matthew J. Frigault, MD: For better or for worse, COVID-19 [coronavirus disease 2019] is here to stay. It will likely be here for the foreseeable future, regardless of our access to a vaccine. The difficulty with COVID-19 has been multifaceted. That includes patient access, patient referral, and patients’ concern for their own safety in coming into the hospital. There are concerns about bringing patients into the hospital safely, treating them, and having enough capacity within hospitals. It’s been multifold. We strive to continue prescribing these products and doing life-saving clinical trials, even through COVID-19, especially given that many of these patients don’t have other options.

Although COVID-19 has complicated things, we have to find newer and more creative ways of dealing with patients, helping them, and getting them to treatment. We’ve adapted more of a virtual approach, so we’re doing a lot of virtual screening from home and trying to limit patient contact with the health care system. We are doing multiple COVID-19 screenings prior to starting chemotherapy and cell infusion, and with fevers following cell infusion. We’re trying to do as much as we can in an outpatient setting to keep patients out of the hospital and avoid capacity issues. Simultaneously, we are balancing the follow-up requirements so they’re not having to come back and forth to a high-risk area multiple times.

Overall, our resources have been stretched thinner. But these are life-saving therapies, so we’re going to find a way to do them. As we look toward a second surge, we’ll hopefully learn from what we went through the first time. Boston was hit pretty hard. Despite that, having over 90% of our hospital at capacity with COVID-19, we were still actively treating patients with CAR [chimeric antigen receptor] T-cell therapy. That was in an isolated unit, and we were able to do so successfully without any complications related to COVID-19 in that population.

It requires a lot of infrastructure, thinking, and commitment. I have to commend the staff for the work they did during that time. I’ll also point out that CAR T cells may, in some ways, help us understand the mechanisms of toxicity related to COVID-19. There are ongoing clinical trials using multiple agents targeting the cytokine storm phenomenon. It is similar to CRS [cytokine release syndrome], although not entirely the same. There is a potential marker, IL-6, that may be associated with COVID-19–related mortality. Altogether, CAR T cells continue to benefit patients. It’s putting stress on the system, but we’re finding ways to deliver care. Hopefully, we can learn something to help in the pandemic from the work we’re doing with toxicity management in CAR T-cell therapy.

Resource utilization has become more complicated because we’re having to put more resources into getting the same amount of work done while keeping patients separate. We have separate elevators, a separate clinic, and separate everything for patients who have COVID-19 and for patients who are at risk of getting COVID-19 or are immunocompromised. That has put a strain on the system. Unfortunately, we’ve also seen a strain on staff. With the way the world has been, a lot of people are having to stay home and take care of their families, which is the right thing to do. But it is stressing the system as we continue to try to push on and move beyond this. From a physical resource perspective, in terms of masks and PPE [personal protective equipment], our institution did a fantastic job allocating those resources.

We’re doing everything we can and are seeing continued growth in our CAR T-cell prescribing and access. Although it’s more heavy lifting on all parts within the hospital, more resource utilization, and doing more with less, we are still able to move forward and will continue to do so. In terms of monitoring patients in the outpatient setting, as we move forward, 1 question is what would happen if we were to have another surge. In general, the majority of patients do just fine. Based on that Stanley Riddell abstract I previously mentioned, about 60% of patients in that cohort were treated outpatient. The median number of days of hospitalization for patients receiving tisagenlecleucel was only 2.

Patients can be safely treated in the outpatient setting. That also helps them avoid contact with the inpatient services. That helps with the capacity issue and with potential risks of exposure from staff and being in the hospital. I do feel that CAR T cells can be given safely in the outpatient setting. Altogether, it’s not so much a safety profile. There is definitely a minimum safety profile. If every patient has severe CRS within 24 hours, there’s no sense in doing it in the outpatient setting.

But for a lot of these products, especially tisagenlecleucel and axicabtagene, the onset of CRS is on the order of days following infusion. Only a very small subset of patients actually have severe and life-threatening CRS or neurotoxicity. As such, you need the infrastructure to be able to deliver the care. You need the nursing education. You need pharmacy for the REMS [Risk Evaluation and Mitigation Strategy] component. You need staffing to see the patients at least daily, early on, and then thereafter.

You need the means to get a patient into the hospital—your hospital, not a local satellite hospital—right away if toxicities are noted. We’ve put systems in place that have patients housed nearby. They’re seen very frequently at multiple points of contact throughout the day. Tocilizumab and steroids are available anytime, as are routine laboratory tests. Continuity of care is preserved so we can assess for neurotoxicity and allow for patient access. This will allow us to treat more patients, hopefully more safely and with multiple products, as we move forward despite COVID-19.

Transcript Edited for Clarity