COVID-19 Raises Difficult Challenges for CAR T-Cell Therapy Administration

The arrival of coronavirus disease 2019 (COVID-19) has caused major disruptions in the administration of chimeric antigen receptor (CAR) T-cell therapy in patients with pediatric B-cell acute lymphoblastic leukemia (ALL) and adult B-cell non-Hodgkin lymphomas (NHL). In a new report, a consortium of investigators offered recommendations for how clinicians should navigate the ongoing hurdles of providing the therapy amid a pandemic.

“The SARS-CoV-2 coronavirus (COVID-19) pandemic presents unprecedented challenges to the delivery of cellular therapy to patients with hematologic malignancies,” wrote corresponding author Peter A. Riedell, MD, of the University of Chicago, and colleagues.

The recommendations were published in the journal Biology of Blood and Marrow Transplantation.

Perhaps the most central question facing providers is whether to continue offering the therapy at all. Riedell and colleagues urged providers to continue the therapy given the high stakes for patients with these cancers.

“Delaying cellular therapy as a consequence of the COVID-19 pandemic is not a realistic option for the overwhelming majority of patients with [relapsed or refractory diffuse large B-cell lymphoma] and ALL, given concerns regarding disease progression and patient demise,” the authors wrote.

That said, providers need to carefully plan out how they will provide the therapy, according to the authors. The authors said FDA patient selection criteria are still operable, and patients should be prioritized if they are highly likely to benefit, have a low risk of toxicity, and/or have no other treatment options. Providers should also be prepared to reschedule or cancel therapies if conditions at their facilities warrant it. Outpatient administration of the therapy is preferable, Riedell and colleagues wrote, and physicians should work with patients to ensure they have some place to go if they are unable to return home following therapy.

One particularly thorny situation that could potentially face clinicians is how to treat a patient who contracts COVID-19 while receiving CAR T-cell therapy or while immunocompromised. In general, the authors said clinicians should monitor the recommendations of the CDC and local public health agencies. Steroids should be used judiciously in these patients, Riedell and colleagues said, given the potential for the drugs to negatively impact COVID-19 outcomes.

“We suggest delaying patients who test positive for a minimum of 14 days from symptom resolution, if feasible, with consideration of interim testing,” the author said.

The authors also noted that telemedicine should be considered whenever possible to limit the risk to patients of contracting or spreading SARS-CoV-2.

Another logistic consideration of which clinicians should be aware is the availability of tocilizumab (Actemra). The recombinant monoclonal antibody to the interleukin-6 receptor has been used in patients receiving CAR T-cell therapy who experience advanced cytokine release syndrome (CRS), and emerging evidence suggests early intervention with the therapy can decrease the severity and duration of CRS. However, the drug is also being used in some patients with COVID-19, which anecdotal reports suggest could lessen or shorten severe respiratory symptoms in these patients. The authors wrote that treatment centers should make sure they have at least 2 doses of tocilizumab available for each patient who undergoes CAR T-cell therapy at their center.

“Patients undergoing CAR T cell therapy are receiving potentially life-saving treatment; therefore, it is paramount to ensure the availability of tocilizumab to mitigate serious toxicity and the need for advanced supportive care measures,” the authors wrote.

In their conclusion, Riedell and colleagues said the burdens on the healthcare system of COVID-19 will mean patients with diffuse large B-cell lymphoma and ALL will find themselves in competition for resources, and thus clinicians must be prepared to strongly advocate on behalf of their patients.

“Today, a deferral of CAR T cell therapy, although with temporary intent, could prove to be permanent and thus eliminate an otherwise potentially curative therapy,” the authors said.

Reference

Bachanova V, Bishop MR, Dahi P, et al. Chimeric antigen receptor T cell therapy during the COVID-19 pandemic. Biol Blood Marrow Transplant. 2020;26(7):1239-1246. doi:10.1016/j.bbmt.2020.04.008