- In chapter 16 of the AEP Online Immunization Manual – dedicated to Immunizations of children with hematopoietic stem cell transplants and solid organ transplants – a section has been added on vaccination recommendations in patients receiving T cell therapy with chimeric receptor (CAR-T).
- Chimeric antigen receptor T cell CAR-T therapy is one of the most promising emerging treatments for hematologic malignancies.
- Vaccination recommendations in these patients are based on the recommendations of expert working groups and consensus of professional associations.
- The vaccination model after CAR-T generally follows the vaccination schedules as in Hematopoietic Stem Progenitor Transplantation.
- Although there are no data on the immunogenicity, efficacy or safety of administering the vaccines in this context, the clinical and immunological status of these patients precludes the use of live attenuated vaccines.
Introduction
In chapter 16 of the AEP Online Immunization Manual dedicated to Immunizations of children with hematopoietic stem cell transplants and solid organ transplants, a section has been added on vaccination recommendations in patients receiving T cell therapy with a receptor. chimeric (CAR-T).
Information on this topic can also be found in chapter 14 of the Manual, which deals with Immunizations in immunosuppressed children or those receiving immunosuppressive treatment.
CAR T cell therapy
Chimeric antigen receptor T-cell therapy (CAR-T) is a form of immunotherapy that recognizes antigens (CD19, BCMA) expressed on neoplastic lineage cells and is one of the most promising emerging treatments for hematological malignancies such as B-cell acute lymphoblastic leukemia, chronic lymphoblastic leukemia, multiple myeloma, and some types of B lymphomas.
The therapy consists of extracting T lymphocytes from the patient through apheresis and obtaining a certain amount of lymphocytes, which are modified so that they recognize and attack tumor cells. Subsequently, they are transferred to the patient so that, after being reprogrammed, they can recognize, attack and destroy cancer cells (Figure X1).
Figure 1. Chimeric antigen receptor T cell therapy (CAR-T)
In addition to acute immunological alterations (neutropenia, side effects of steroids or tocilizumab, etc.), its use produces prolonged myelosuppression and immunodeficiency. Anti-CD19 CAR-T cells lead to complete elimination of B cells with consequent hypogammaglobulinemia. Anemia, neutropenia, thrombocytopenia, and CD4 lymphopenia of variable duration also occur. CD4 lymphopenia ≤200/mm3 can persist for up to a year, while hypogammaglobulinemia (≤400 mg/mm3) secondary to B lymphocyte depletion can last up to 5 years, sometimes requiring replacement therapy with immunoglobulins.
Anti-CD19 CAR-T therapy has recently also been used for autoimmune diseases such as systemic lupus erythematosus (SLE) and idiopathic inflammatory myositis.
Due to B lymphocyte depletion, the humoral response to vaccines is severely compromised and very few patients achieve protective antibody titers. However, almost 90% of them develop CD4 and CD8 T responses.
In subjects treated with BCMA CAR-T therapy used in multiple myeloma, all plasma cells are destroyed, so the impact is likely to be greater. Only 14% of patients who do not receive immunoglobulin replacement therapy have antibodies against pneumococcus, between 3 and 20 months after the infusion.
It is not known exactly what the impact of cell therapies is on the levels of antibodies against pathogens prior to treatment. Although anti-CD19 CAR-T therapies eliminate memory B cells and plasma cells, the proportion of subjects with seroprotection against vaccine-preventable diseases is similar to that of the general population. This is probably due to the persistence of a population of CD19 plasma cells. However, with BCMA CAR-T cell therapy the proportion of subjects with seroprotection is only 50%.
The response to vaccines in patients receiving CAR-T therapy has been based, above all, on the response to vaccines against SARS-CoV-2. These studies have shown a decreased response compared to healthy people. The response to pneumococcal vaccination with conjugate vaccines is particularly poor, even several months after infusion.
Vaccination recommendations in patients with CAR-T cell therapies are based on recommendations from expert working groups and consensus from professional associations. As occurs in other states of acquired programmed immunosuppression, It is essential that patients are up to date with the vaccination schedules according to their age before the procedure.. Vaccination against influenza and SARS-CoV2 must be carried out in all of them at least 2 weeks before the infusion.
General vaccination recommendations in patients treated with CAR-T therapy
Inactivated vaccines
They can be administered 3 months after cell therapy, as long as there is immune reconstitution (CD4 lymphocytes >200/mm3 and CD19 or CD20 lymphocytes >20/mm3).
Some authors also recommend IgA levels >6 mg/dl as evidence of the existence of the switching capacity of immunoglobulins and that there is no active immunosuppression. Likewise, it requires that patients have not received intravenous immunoglobulins in the previous 2 months and that anti-CD19 or anti-CD20 antibodies have not been used in the previous 6 months.
The only exception is the flu and SARS-Cov-2 vaccination, which should be carried out annually, regardless of the previous conditions.
Live attenuated vaccines
They can be administered after 12 months of cell therapy, as long as there is immune reconstitution (CD4 lymphocytes >200/mm3 and CD19 or CD20 lymphocytes >20/mm3). As in the previous case, some authors also recommend IgA levels >6 mg/dl and absence of active immunosuppression.
It is required that patients have not received intravenous immunoglobulins in the previous 8 months, that they have not used anti-CD19 or anti-CD20 antibodies in the previous 6 months, and that they have not undergone a hematopoietic stem cell transplant (HSCT) in the previous 2 years.
The vaccination model after CAR-T therapy follows the HSCT vaccination schedules.
– oOo-
Literature
- Arya S, et al. Overview of infections complications among CAR T-cell therapy recipients. Frontiers Oncol 2024;14:1398078.
- Brudno JM, et al. CAR T Cells and T-Cell Therapies for Cancer. A Translational Science Review. JAMA. 2024 Nov 4. doi: 10.1001/jama.2024.19462. Online ahead of print.
- Ge C, et al. Serologic response and safety of COVID‑19 vaccination in HSCT or CAR T‑cell recipients: a systematic review and meta‑analysis. Exp Hematol Oncol. 2022;11:46.
- Hill JA, et al. How I prevent infections in patients receiving CD19-targeted chimeric antigen receptor T cells for B-cell malignancies. Blood 2020;136:925-35.
- Lee D, et al. Pneumococcal Conjugate Vaccine Does Not Induce Humoral Response When Administrated Within the Six Months After CD19 CAR T-Cell Therapy. Transplant Cell Ther. 2023;29:277.e1-9.
- Reiman H, et al. Cellular and humoral immune responses to SARS-CoV-2 vaccination in patients after CD19.CAR T-cell therapy. Blood Adv. 2023;7:2066-9.
- Reynolds G, et al. Vaccine schedule recommendations and updates for patients with hematologic malignancy post-hematopoietic cell transplant or CAR T-cell therapy. Transpl Infect Dis. 2023;25 Suppl 1:e14109.
- Walt CS, et al. Antibodies against vaccine-preventable infections after CAR-T cell therapy for B cell malignancies. JCI Insight. 2021;6:e146743.
- Wu Xi, et al. Immune response to vaccination against SARS‑CoV‑2 in hematopoietic stem cell transplantation and CAR T‑cell therapy recipients. J Hematol Oncol. 2022;15:81.
More information on this website
– CAV-AEP. Immunizations of children with hematopoietic stem cell transplant and solid organ transplant. Vaccination recommendations in patients receiving chimeric receptor T-cell therapy (CAR-T), in the AEP Online Immunization Manual.
– CAV-AEP. Immunizations in immunosuppressed children or children with immunosuppressive treatment, in the AEP online Immunization Manual.
– CAV-AEP. Other news about special situations.
– CAV-AEP. Other news about the AEP Online Immunization Manual.
A Deep Dive into CAR-T Therapy Vaccination Recommendations
Well, well, well! Welcome to the wonderful world of CAR-T therapy and vaccinations. You might be thinking, “Vaccinations and cancer treatment? Where’s the punchline?” But trust me, if you think the world of immunology isn’t ripe for comedy, you’ve never seen a germ trying to figure out what’s your immune system doing! A bit cheeky, I know, but let’s dig in, because when it comes to immunizations in patients receiving CAR-T therapy, the stakes are anything but funny.
In a Nutshell
- Chapter 16 of the AEP Online Immunization Manual is now giving you the lowdown on vaccination recommendations for those brave souls undergoing T cell therapy with CAR-T. Yes, folks, if you’re not impressed, you haven’t been paying attention!
- CAR-T therapy is quite the superhero; it’s one of the most promising treatments for hematologic malignancies. Move over, Batman. This one saves lives!
- All recommendations for vaccinations are curated by expert teams and associations. These people know their business—like a well-organized team of spies, but with less drama and more graphs.
- In short, vaccination schedules can mirror those used post-Hematopoietic Stem Progenitor Transplantation. Spoiler alert: It’s complicated!
- No live vaccines here, folks! Safety first, especially when your immune system is taking a sabbatical.
CAR-T Therapy: A Not-So-Secret Weapon
Chimeric antigen receptor T-cell therapy (CAR-T)—the name alone sounds like a new sci-fi gadget, doesn’t it? But really, this immune treatment targets nefarious cells that are way too fond of the spotlight, like those pesky B-cell malignancies. From leukemia to lymphomas, CAR-T is out there fighting the good fight!
The mechanics of this therapy are like a complex dance—T lymphocytes get the extraction treatment through apheresis, get reprogrammed, and, in the end, they’re sent back in to kick cancer’s butt! But beware! This cocktail comes with side effects that could make a grown man cry, like prolonged myelosuppression and immunodeficiency akin to a toddler going without naptime.
These immune-challenged warriors are left with a longing for B cells, leading to what we call hypogammaglobulinemia—fancy words for saying your body’s defenses aren’t quite up to speed. Why not just say they’re “on vacation,” right?
Now, on to Vaccination Recommendations
Right, so here’s where it gets trickier than a toddler with a cookie jar: vaccinating these patients. Research shows their ability to respond to vaccines is about as reliable as a dodgy Wi-Fi connection! After CAR-T therapy, recommendations recommend waiting for the immune system to show signs of life again—now, granted, this is a waiting game that can be testing.
Inactivated vs. Live Attenuated Vaccines
Inactivated vaccines? Sure, you can throw those in there three months post-cell therapy, but only if your CD4 lymphocytes are back above a certain level—think of it as your immune system’s own version of a bouncer at the club.
Now, live attenuated vaccines are the Hollywood divas of vaccines: they can only come out after 12 months with all the right credentials—again, we’re talking about levels of CD4 lymphocytes among other criteria. If you’ve had a hematopoietic stem cell transplant in the last two years, that’s a massive “sorry, you’re not on the list” moment!
The Bigger Picture
What’s the gist? Well, as fascinating as all this sounds, vaccination after CAR-T therapy is like trying to navigate a carnival maze while blindfolded. Basically, you optimally want patients up-to-date with their vaccinations before they even start the CAR-T fiesta. And, for the love of all things holy, flu vaccines should be held before the therapy—like a red carpet event without the paparazzi!
Now, while it feels like a fight against insurmountable odds, experts recommend keeping the dialogue alive. It’s all about making sure these patients don’t just survive—they thrive! Staying vaccinated and well-informed offers the real promise of new beginnings.
Parting Shots
So, my dear readers, as we contemplate the conundrum of vaccinations in CAR-T therapy, remember that while the science might have some twists, there’s always a light-hearted moment waiting just around the corner. It’s a precarious dance of immune responses, but like all great productions, it’s better with a bit of contagious laughter—even if it’s at the expense of a very serious topic.
And who knew immunology could be this entertaining? Just goes to show you that whether it’s CAR-T cancer therapy or crafting a new joke, timing—and timing of vaccinations—really is everything!
Stay safe, stay smart, and keep those vaccines top of mind!
Why are CD4 lymphocytes compared to a nightclub bouncer in relation to CAR-T therapy and vaccination timing?
A nightclub. If the bouncer (CD4 lymphocytes) isn’t letting anyone in, it’s probably too soon for a party (vaccination). As for live attenuated vaccines? Just keep those under wraps for at least two years after CAR-T therapy. Better safe than sorry!
The Impact of COVID-19 Vaccination
With the global pandemic turning the world on its head, you might be wondering how the COVID-19 vaccination fits into this equation. Patients who have undergone CAR-T therapy have shown varied responses to the COVID-19 vaccine. Studies indicate a less robust immune response, especially for those vaccinated within the six-month window post-therapy. So, it’s crucial to take additional precautions during those early months.
Literature Says It All
For those interested in a more serious dive into the data, the references in the earlier section provide a treasure trove of information on infection risks, immune responses post-vaccination, and specific studies about vaccine efficacy in CAR-T patients. Make sure to check them out if you’re a fan of the fine print!
The Bottom Line
Vaccinating patients post-CAR-T therapy is a delicate balance of timing, type of vaccine, and monitoring immune recovery. As a healthcare professional, staying abreast of the latest recommendations and literature is vital to ensuring that these remarkable patients receive the comprehensive care they deserve. And remember, when in doubt—consult the experts and prioritize patient safety above all else!
In conclusion, CAR-T therapy is an incredible advancement in cancer treatment, but navigating the complexities of vaccination for these patients requires diligence, understanding, and a little humor along the way. Stay informed, stay safe, and remember that your immune system, like your favorite superhero, will eventually rise to the occasion!
