CAR T Treatment and Infection Risk in the Age of SARS Cov-2

An article titled “State of the CAR-T: Risk of Infections with Chimeric Antigen Receptor T-Cell Therapy and Determinants of SARS-CoV-2 Vaccine Responses” was published very recently in the journal Transplantation and Cellular Therapy. This article is worth attention by past and future CAR-T recipients. Its focus is on understanding and managing infection risk in CAR-T cell treatment recipients.

A number of different CAR-T treatments, targeting CD19 and BCMA,  have already been approved by the US Food and Drug Administration (FDA) to treat several hematological malignancies such as Relapsed/Refractory (RR) Acute Lymphoblastic Leukemia, RR Diffuse Large B-Cell Lymphoma (and other lymphomas that share similar features of DLBCL), Relapsed/Refractory Mantle Cell Lymphoma, and more recently the approval of the anti-BCMA product ide-cel (Bristol Myers’ Abecma) for the treatment of Relapsed/Refractory Multiple Myeloma. In addition, the anti-BCMA CAR-T “cilta-cel” (from Johnson and Johnson) is currently under review by FDA with an approval action date during February 2022.

The authors clearly state early in the article: 

“Although CAR-T therapy prolongs the survival of patients with R/R diseases, the associated on-target off-tumor toxicities, particularly infections, limit the effective utilization of this curative therapy.”[emphasis added]

The article discusses infection risk for the hematological malignancies for all the illnesses listed in the first paragraph but, somewhat unfortunately, to a lesser extent for MM considering the very limited patient experiences with the anti-BCMA products. Still, a number of observations and conclusions are very relevant for us, myeloma patients.

With respect to infections the authors make the following observations in Table 1 of the article titled “Patient-, Disease-, and CAR-T Therapy-Related Factors Potentially Associated with the Risk of Infections.”

General factors that impact infection risk related to CAR-T treatment

Below is a summary of risk factors specifically for myeloma patients with CAR-T treatment: 

General factors that impact infection risk related to CAR-T treatment for myeloma patients

Specifically with respect to SARS-CoV-2 vaccination, the authors make the following points. (Please note that the items below are just “snippets” from several pages of discussion presented in the above referenced article. I encourage patients slated to go for CAR-T treatment to read the full article, especially since it is written in comprehensible language.

• The American Society of Transplantation and Cellular Therapy, American Society of Hematology, and National Comprehensive Cancer Network currently recommend the administration of mRNA SARS-CoV-2 vaccines as early as 3 months following CAR-T.”
• "… efficacy and safety in the general population and acknowledge that [Covid vaccine]efficacy may be reduced among recipients of cellular therapy compared with the general population.”
• “Diminished vaccine responses have been described in patients with CLL and MM.”
• “In addition to concerns related to suboptimal efficacy, CART recipients theoretically could have an elevated risk of immune-mediated toxicity.”
• “Immunocompromised patients are at increased risk for shedding of the replication-incompetent virus [22,51]. Patients with hematologic malignancies undergoing active treatment, particularly B-cell-depleting therapy such as CAR-T, are at a higher risk for prolonged viral shedding.”

The overall gist of this post may scare the daylight out of some patients.

Before closing I would like to quote the opening line of the referenced article. “Chimeric antigen receptor T cell (CAR-T) therapy has shown unprecedented response rates in patients with relapsed/refractory (R/R) hematologic malignancies.” THIS is what matters. CAR-T treatment is projected to be a true game changer in the treatment of multiple myeloma.

Infection risk has been with us from the first day of our treatment. It is something to be aware of in our daily life and something we can also mitigate ourselves by being careful at home and in our public interaction with others.