Authors
Viktoria Blumenberg, David J Bozym, Maxx King, Marisa G Ogier, Deshea L Harris, Keshav Sridharan, Jing Li, Patrick C Johnson, Benjamin R Puliafito, Alexandra M Haugh, Jacob D Soumerai, Julie E Haydu, Elliot C Woods, Jeremy S Abramson, Yi-Bin Chen, Mark B Leick, Kathleen Me Gallagher, Marcela V Maus, Matthew J Frigault
Published in
Blood cancer discovery. Oct 19, 2026. Epub Oct 19, 2026.
Abstract
Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) affect most patients receiving axicabtagene ciloleucel (axi-cel) for relapsed or refractory large B-cell lymphoma (LBCL). Based on pre-clinical data, we hypothesized that prophylactic IFN-γ blockade could prevent toxicity without impairing efficacy. We initiated an open-label phase 2 trial (NCT06550141) evaluating single-dose emapalumab one day before axi-cel. Here, we report the first two patients to caution against the pre-emptive emapalumab use prior axi-cel: Both developed treatment-refractory toxicities including high-grade ICANS and overlapping CRS-IEC-HS requiring multiple immunomodulatory agents. CAR T-cell expansion exceeded levels reported in ZUMA-1 and a standard-of-care axi-cel cohort at our institution. Despite therapeutic emapalumab and suppressed free IFN-γ, IL-2 and sIL-2R were markedly elevated, suggesting CRS was driven independent of IFN-γ. Both patients achieved complete responses, suggesting preserved efficacy. Given the unanticipated severity and refractoriness of toxicities, recruitment with this design was discontinued and the protocol was amended.
PMID:
42896102
Bibliographic data and abstract were imported from PubMed on 20 Oct 2026.
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