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EBMT 2025 | Late hematotoxicity of CD19-directed CAR-T in patients with LBCL
Parastoo Dahi, MD, MS, Memorial Sloan Kettering, New York City, NY, presents the findings of a retrospective multicenter study investigating the prevalence and outcomes of late hematotoxicity in patients with relapsed/refractory (R/R) large B cell lymphoma (LBCL) receiving CD19-directed CAR T-cell therapy. Cytopenia was the most prevalent toxicity observed, and Dr Dahi highlights that a high CAR HAEMATOTOX score (greater than 2) was associated with this complication at three and six months post-infusion. This interview took place at the 51st Annual Meeting of the EBMT in Florence, Italy.
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Transcript
On behalf of the Cellular Therapy Consortium in the United States, which consists of eight academic institutions in the United States, I presented the data on late hematotoxicity after CD19-directed CAR T-cell therapy. We looked at the prevalence – it was quite prevalent at one month, two months, through 12 months. We looked at the cytopenias grade three and higher by CTCAE criteria...
On behalf of the Cellular Therapy Consortium in the United States, which consists of eight academic institutions in the United States, I presented the data on late hematotoxicity after CD19-directed CAR T-cell therapy. We looked at the prevalence – it was quite prevalent at one month, two months, through 12 months. We looked at the cytopenias grade three and higher by CTCAE criteria. At one month, there was about 29% cytopenias. At two months, there was still a good number, like 15% of the patients had cytopenia. At three months, it was 12 percent; at six months, 10 percent; at nine months, 12 percent; and at 12 months, it was four percent. Then, even at 12 months, still three percent of the patients had clinically significant cytopenias.
We looked at the associations between cytopenias and outcomes, and while there was no association with age, multiple prior lines of therapies, ICANS, CRS, or bridging therapy, the only factor that was associated with late cytopenias was a high HEMATOTOX score, basically both at three and six months.
And when we looked at the survival data, patients who had cytopenia, their survival, their overall survival was not different from those that did not have. But looking at the non-relapse mortality, those patients who did have cytopenia actually had significantly higher non-relapse mortality than those without cytopenia, and most of the mortality was driven by infection – about a third of the patients died from infection.
And so basically, this is a real-world setting that we still see that cytopenia is probably the most prevalent toxicity of CAR T-cells, and we need studies to understand the pathophysiology of the late cytopenias and manage these cytopenias based on the pathophysiology.
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