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CAR-T Meeting 2022 | Challenges for CAR-T therapies during the COVID-19 pandemic

Mohamad Mohty, MD, PhD, Saint-Antoine Hospital, Paris, France, talks on the impact of the COVID-19 pandemic on treating patients with hematological malignancies with chimeric antigen receptor T-cell (CAR-T) therapies. The pandemic led to a shortage in ICU hospital beds which are sometimes required to treat patients experiencing severe CAR-T-related side effects including cytokine release syndrome (CRS) and neurotoxicity. Moreover, COVID-19 infection prior to CAR T-infusion represents a major challenge for patients with hematological malignancies who are highly immunosuppressed, as it may result in treatment delay. In addition, management strategies for patients infected with COVID-19 prior to the start of CAR-T therapy are currently not well established. Prof. Mohty emphasizes the importance of vaccination against COVID-19 in patients with hematological malignancies. This interview took place at the EBMT-EHA 4th European CAR T-cell Meeting which was held virtually in 2022.

Transcript (edited for clarity)

The question about the impact of COVID-19 and CAR-Ts is really a very challenging and important question. I think the pandemic represented a huge challenge for the administration of CAR-Ts, but also for performing stem cell transplantation whether autologous or allogeneic in general. There are several reasons for this: of course, logistical reasons, hospitals beds being overwhelmed with COVID patients, but also the shortage of ICU beds in different places and different countries...

The question about the impact of COVID-19 and CAR-Ts is really a very challenging and important question. I think the pandemic represented a huge challenge for the administration of CAR-Ts, but also for performing stem cell transplantation whether autologous or allogeneic in general. There are several reasons for this: of course, logistical reasons, hospitals beds being overwhelmed with COVID patients, but also the shortage of ICU beds in different places and different countries. In CAR-Ts, I think one key challenge is about the potential risk of cytokine release syndrome and neurotoxicity, which can usually require the use of ICU beds. This has been a challenge and obviously it was very important to secure a few beds for these patients before embarking on this.

The other issue is about the infection with the COVID-19 virus itself. Unfortunately, usually these patients are highly immunosuppressed, whether lymphoma, ALL, or myeloma patients. Many of these patients after such a severe COVID-19 infection would be in a bad general status and may not be fit or eligible for CAR-Ts.

The other issue one can face is about the discovery of COVID-19 infection immediately before CAR-T infusion. That would require depending on the clinical status of the patient to delay the infusion. We have also experienced a situation where the infection was discovered after the infusion of these CAR-Ts. This creates a lot of anxiety for the patient, but also for the healthcare professionals because it is not easy or well established how to manage a patient receiving CAR-Ts, but at the same time experiencing an infection. Obviously, it depends whether this is a symptomatic infection versus just a discovery of a positive PCR. Of course, today we do have some prophylactic antibodies that are proving to be useful. Of course, I would insist on the fact that whether candidate for CAR-Ts or not, all immunosuppressed and hematology patients should be vaccinated. Of course, we know very well that not all of them will respond very well to the vaccine, but still I think overall there is an important and significant benefit for everybody. At the end of the day, I think the COVID-19 pandemic has been really challenging when it comes to treating patients with hematological malignancies. I think all efforts should be directed towards avoiding any loss of chance in allowing these patients to receive state-of-the-art therapy. I believe most of the teams, if not all of them managed to do this and this is really great news for our patients.

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