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CAR T Treatment and Infection Risk in the Age of COVID-19
CAR T Treatment and Infection Risk in the Age of COVID-19 image
CAR T Treatment and Infection Risk in the Age of COVID-19
Posted Nov 29, 2021

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.”

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

 

Factors decreasing infection risk

Factors increasing  infection risk

  • Disease in remission at time of CAR-T

  • Longer time interval between prior stem cell transplant (SCT) and CAR-T

  • Longer interval between date of diagnosis and CAR-T

  • Shorter interval between apheresis (T-cell collection) and CAR-T infusion

  • Lower risk for patients with more recent CAR-T (due to improved supportive and prophylactic care).

  • Higher for patients with more prior lines of treatment

  • Higher for patients with CNS involvement

  • Higher age of the patient

  • Higher for ethnic minorities (African American, Hispanic, Pacific Islander)

  • Higher for patients with higher Body Mass Index (BMI)

  • Higher for patients with a higher “Karnofsky Score” (a measure that attempts to quantify cancer patients' general well-being and activities of daily life) – a higher score indicates lower patient performance.

  • Higher for patients with a higher burden of comorbidities.

  • Higher for patients with prolonged cytopenia (reduced production of any of red blood cells, white blood cells, platelets)

  • Higher for patients with higher dose of CAR-T cells

  • Higher for patients with higher doses of lymphodepleting chemotherapy prior to CAR-T

  • Higher if bridging therapy needs to be used between the period of T-Cell harvest and CAR-T infusion

  • Higher risk for bacterial infections in patients with treatment that targets CD-19

  • Higher risk for viral (and overall) infections in patients with treatment that targets BCMA.

  • Diminished vaccine responses in patients with treatment that target BCMA

  • Higher for patients with more severe cytokine release syndrome

  • Higher for patients treated with steroids and tocilizumab (due to cumulative immunosuppression)

 

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 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 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.

The author Paul Kleutghen

about the author
Paul Kleutghen

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.

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