CAR-T Meeting 2021 | Infection prevention in patients receiving CAR T-cells

Infection prevention and supportive care for these patients, I think, is really critical, and this is going to evolve a lot as we learn more and as products change and the target of the product changes, as well, and the types of immunodeficiencies that we see change and underlying diseases. So far, we were given the opportunity to write an article for the “How I Treat” series in the Blood Journal, along with Dr. Syed from Memorial Sloan Kettering, where we laid out some expert kind of opinions about how we might approach this.

A lot of this is really taken from the literature that’s been developed over the past few decades in patients with autologous and also allogeneic bone marrow transplant, and most institutions are protecting their patients with levofloxacin or a fluoroquinolone during periods of neutropenia. In most patients, that tends to be brief, around seven to 10 days, although certainly we do see prolonged cytopenias. We also give fluconazole or micafungin during that time period of neutropenia. And then all patients should be on antiviral prophylaxis with acyclovir for at least six months to 12 months after their CAR T-cell therapy, in addition to trimethoprim sulfamethoxazole for pneumocystis prophylaxis. That’s kind of the core background.

Think there’s lots of discussion in the field in general in cancer patients about whether we need antibacterial prophylaxis during neutropenia, and that’s something that’s an open debate, I think. We really think about escalating our prophylactic approaches in patients who do have severe cytokine release syndrome or severe neurotoxicity and are in the ICU, so that’s a setting in which one might think about escalating to antimold prophylaxis and maybe monitoring for CMV, although we really don’t know much about those infections in that context. And that’s the general approach. IVIg we really reserve for patients with very low levels of total IgG and recurrent or severe bacterial infections primarily, and we really don’t know exactly who and when to give those products to. And partly, that might be affected by which B-cells are depleted by the CAR T-cell product and how patients’ immune systems recover.

And then finally, in that article, we gave some suggestions regarding vaccinations and vaccination strategies. And for that, we really recommended starting around six months or so after CAR T-cell therapy in appropriate patients and seeing how they respond. And if there’s no evidence of a response, it likely makes sense to wait until additional markers of immune recovery have occurred, such as improving CD4 counts, detectable B-cells in the blood, and then some signs of IgA production, as well, may guide that. But we really don’t know how well those predict a vaccine response. Lots of work to be done there. In the US, we are recommending consideration for a coronavirus vaccine as early as three to six months after transplant and CAR T-cell therapy. But once again, a lot to be learned in that area.