CAR-T Meeting 2023 | Management strategies for early and late infections in patients undergoing CAR-T cell therapy
Andriyana Bankova, MD, University Hospital Zurich, Zurich, Switzerland, gives an overview of management strategies for early and late infections following treatment with CAR-T therapy. Dr Bankova first discusses the use of prophylactic antibiotics, antivirals and antifungals, and then goes on to highlight the role of granulocyte colony-stimulating factor (G-CSF) prophylaxis in patients undergoing CAR-T therapy. To conclude, Dr Bankova comments on the novel CAR-HEMATOTOX score, which is being used to risk stratify patients being treated with CAR-T cells. This interview took place at the EBMT-EHA 5th European CAR T-cell Meeting held in Rotterdam, The Netherlands.
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Transcript (edited for clarity)
So basically, besides CRS and ICANS, infections are among the most common complications in patients undergoing CAR-T cell therapies, and we actually do not hear a lot about these complications, and this was the reason that we decided to basically discuss this in one of the nurse sessions in this yea’sr CAR-T cell meeting.
We now basically have recommendation on the prophylactic and management strategy for infections for CAR-T cell therapy, and these are mostly adopted from practice guidelines used in recipients of hematopoietic stem cell transplantation...
So basically, besides CRS and ICANS, infections are among the most common complications in patients undergoing CAR-T cell therapies, and we actually do not hear a lot about these complications, and this was the reason that we decided to basically discuss this in one of the nurse sessions in this yea’sr CAR-T cell meeting.
We now basically have recommendation on the prophylactic and management strategy for infections for CAR-T cell therapy, and these are mostly adopted from practice guidelines used in recipients of hematopoietic stem cell transplantation. We also now have a panel of experts that updated the guidelines of the EBMT, JC and EHA in 2021. And now, what we recommend is, for sure antibacterial prophylaxis, only in some cases, not all cases, for example, cases which have prolonged neutropenia should be considered for antibacterial prophylaxis. Patients that also have a prolonged use of corticosteroids should be considered for prophylaxis, but we are not giving it on a routinely basis.
What we do at that point, in all patients, and this is also being recommended by most of the guidelines, is antiviral prophylaxis with acyclovir or valacyclovir, basically starting from the time of lymphodepletion up to six to 12 months. And also, [inaudible 0:00:02:06] prophylaxis with co-trimoxazole, again starting from the time of lymphodepletion until six to 12 months. Some guidelines recommend before stop of this prophylactic treatments also to measure the count of CD4 cells, and if this is above 200 per microliter, to stop the prophylaxis.
Antifungal prophylaxis is also not routinely recommended in patients with prior allogeneic hematopoietic stem cell transplantation, prior invasive aspergillosis patients receiving corticosteroids, also [inaudible] prophylaxis should be considered. This is also the recommendation from the panel of experts, but again, we do not routinely give at that point. This might change, of course, in the future, but at that point, we only try to select risk patients and only those receive fungal prophylaxis.
Also, very important as we know, neutropenia is a side effect of CAR-T cell therapy, and severe neutropenia and prolonged neutropenia is being seen in patients post-CAR-T cell, in particular in the early phase until day 13. So here, it is recommended to apply simulation with G-CSF, for example, in patients following day 14, which basically still have not resolved their neutropenia. Some guidelines recommend now the start of G-CSF a lot earlier. There are centers starting G-CSF stimulation very early post-CAR-T cell infusion in the first week. We, in our center, we still don’t apply G-CSF as early, but I think here, we will have coming data showing that CRS and ICANS may be really not such an issue for patients receiving G-CSF prophylaxis, so this is still an ongoing debate how early you can start and do you really need to make sure that the patient does not have CRS and ICANS which have not resolved before you start G-CSF.
Also, something we do and is being recommended is intravenous immunoglobulin substitution. We know that patients undergoing CAR and CD19 and BCMA CAR-T cell therapy have a very prolonged hypogammaglobulinemia in the adult setting. It is recommended to substitute if immunoglobulin levels are below four grams per liter.
In regard of tools and how we might be able to assess patients at risk, we now know from the group from Germany that there is a tool, the so-called, CAR-HEMATOTOX tool. So there are also now retrospective data showing that basically patients with a high score in the CAR-HEMATOTOX, which is based on neutrophil count, platelet count, ferritin, CRP, for the lymphodepletion, basically patients with high CAR-HEMATOTOX are at increased risk to develop severe infection. So I believe this is also something that is going to be now more studied also in a prospective manner, so it will be really very interesting to see what might be the recommendation there basically using the CAR-HEMATOTOX tool. At our center, we also started to use this tool just to see which patients might be at increased risk of prolonged cytopenia and also of severe infections post CAR-T cell treatment.
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