CAR-T Meeting 2023 | Managing hematologic toxicity associated with CAR-T therapy & insights into the CAR-HEMATOTOX score
Marion Subklewe, MD, Ludwig-Maximilians University of Munich, Munich, Germany, comments on the importance of improving methods of assessing and managing hematologic toxicity associated with the use of CAR-T therapy. Prof. Subklewe also shares some insights into the novel CAR-HEMATOTOX risk stratification tool being evaluated in patients treated with CAR-T therapy for various hematological malignancies. 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)
Hematotoxicity is the most common immune-related adverse event after CAR-T cell therapy, and it actually occurs independent of the disease setting. It has been described in the setting of ALL, large B-cell lymphoma, also multiple myeloma, mantle cell lymphoma. It also has been reported independent of the target antigen. So in the context of CD19 CAR-T cells, as well as BCMA-directed CAR T-cells...
Hematotoxicity is the most common immune-related adverse event after CAR-T cell therapy, and it actually occurs independent of the disease setting. It has been described in the setting of ALL, large B-cell lymphoma, also multiple myeloma, mantle cell lymphoma. It also has been reported independent of the target antigen. So in the context of CD19 CAR-T cells, as well as BCMA-directed CAR T-cells.
And we know that hematotoxicity predisposes to infectious complications, and again, infectious complications are the most common cause of non-relapse mortality post-CAR-T cell. So I think it’s highly relevant and we have published in the context of large B-cell lymphoma utilizing commercial CAR-T cells in third-line, the incidence of severe hematotoxicity, which is about 25% of the patients. And in general, also reports from others, we have about 30 to 35% severe infections within the first 30 days.
We have developed a CAR-HEMATOTOX score, which integrates neutrophil counts, hemoglobin, platelet, but also the inflammatory markers, CRP and ferritin, assessed prior to the start of lymphodepletion. And we could show that a HEMATOTOX score high versus low is associated with a markedly increased risk of infectious complications.
We could now apply the score, which was developed in large B-cell lymphoma, validated in large B-cell lymphoma, and we now applied the score also in the setting of multiple myeloma, but also mantle cell lymphoma. And we could again discriminate for patients a high and low score with a prolonged time of neutropenia, defined as neutrophil counts below 500 for longer than 14 days. And that was again associated with an increased rate of infectious complications.
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