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ASH 2024 | Radiation therapy and monocyte activation in patients with LBCL treated with CAR T-cell therapy
Paolo Strati, MD, The University of Texas MD Anderson Cancer Center, Houston, TX, comments on an investigation into the impact of radiation therapy as a bridging therapy before CAR T-cell infusion in patients with large B-cell lymphoma (LBCL). Dr Strati highlights that radiation therapy is safe and effective in increasing the rate of circulating monocytes and dendritic cells, which exhibit enhanced anti-tumoral properties. However, he also notes that a subset of these cells may express CSF1R, a receptor associated with a more pro-tumoral phenotype, a factor that will likely need to be addressed to optimize treatment outcomes. This interview took place at the 66th ASH Annual Meeting and Exposition, held in San Diego, CA.
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Transcript (AI-generated)
When it comes to large B-cell lymphoma, we currently have no standard bridging therapy to utilize before CAR-T cell infusion. And as a reminder, we define bridging therapy as the treatment that we provide between leukapheresis and initiation of lymphodepleting chemo. We have previously published data showing that radiation therapy can be a very safe and effective bridging therapy before CAR-T cell infusion in large B-cell lymphoma patients...
When it comes to large B-cell lymphoma, we currently have no standard bridging therapy to utilize before CAR-T cell infusion. And as a reminder, we define bridging therapy as the treatment that we provide between leukapheresis and initiation of lymphodepleting chemo. We have previously published data showing that radiation therapy can be a very safe and effective bridging therapy before CAR-T cell infusion in large B-cell lymphoma patients. But we’re unable to demonstrate the biological rationale for that.
So we collected prospectively blood samples from large B-cell lymphoma patients who were receiving bridging radiation before standard of care, autologous, anti-CD19-CAR-T cell therapy. And we performed on those samples collected before initiation of radiation and at the end of bridging radiation, bulk RNA sequencing with the convolution in collaboration with Boston Gene.
What we have been able to demonstrate is that bridging radiation was meaningfully increasing the rate of circulating monocytes and dendritic cells. But most importantly, the bridging radiation was also increasing their anti-tumoral properties in terms of proliferation and cytotoxicity and anti-tumoral activity overall. Of interest, despite increase in anti-tumoral phenotype, there’s also a monocyte population that increase at the end of radiation, bridging radiation, and they all express a receptor called CSF1R, which is known to be associated with overall a more actually pro-tumoral phenotype, representing a potential Achilles’ heel for future treatment and providing the rationale for potentially combined bridging radiation to CSF1R targeting agents such as axatilimab, an agent currently approved by the FDA for GvHD.
We’re now trying to expand our study and also have some validation with the clinical work, but hopefully we will be able, based on this data, to develop new trials where we will be able to enhance the activity of bridging radiation before CAR-T.
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Disclosures
Abbvie-Genmab: Consultancy; Acerta-Astrazeneca: Consultancy, Research Funding; Sobi ADC Therapeutics: Consultancy, Other: Travel, accommodations, expenses, Research Funding; Kite, a Gilead company: Consultancy, Research Funding; Roche-Genentech: Consultancy; ALX Oncology: Research Funding; Ipsen: Consultancy; Hutchison MediPharma: Consultancy; TG Therapeutics: Consultancy.
