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. While there has not been a CAR-T cell treatment that has been FDA approved for acute myeloid leukemia at this time, there are over 40 open CAR-T clinical trials for AML patients to join.
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 AML considering the very limited patient experiences. Still, a number of observations and conclusions are very relevant for us AML 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.”
Factors decreasing infection risk
Factors increasing infection risk
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 the 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 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 hoped to be a true game-changer in the treatment of acute myeloid leukemia.
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.
about the author
I am a patient diagnosed in 2014 with primary plasma cell leukemia (pPCL), a rare and aggressive variant of multiple myeloma and have been very fortunate to find successful treatment at the division of Cellular Therapy at the Duke University Cancer Institute. My wife, Vicki, and I have two adult children and two grandsons who are the ‘lights of our lives’. Successful treatment has allowed Vicki and I to do what we love best : traveling the world, albeit it with some extra precautions to keep infections away. My career in the pharmaceutical industry has given me insights that I am currently putting to use as an advocate to lower drug pricing, especially prices for anti-cancer drugs. I am a firm believer that staying mentally active, physically fit, compliant to our treatment regimen and taking an active interest in our disease are keys to successful treatment outcomes.