Roni Shouval: CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma
Roni Shouval, Assistant Attending of Bone Marrow Transplantation and Cellular Therapy Service and Principal Investigator of Precision Cellular Therapy Research Group at Memorial Sloan Kettering Cancer Center, shared a post on X about a paper he co-authored with colleagues published in Blood Cancer Journal:
“CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma”
Authors: Alejandro Luna, Sean Devlin, Kai Rejeski, Jessica Flynn, Magdalena Corona, Brandon Imber, Gilles Salles, Jae Park, Miguel-Angel Perales, Roni Shouval et al.
“Excited to share our new study in Blood Cancer Journal led by Alejandro Luna.
‘CAR T-cell therapy response varies by extranodal disease site in large B-cell lymphoma.’
We asked:
Do specific anatomical sites act as sanctuaries from CAR T?
We analysed 958 PET-CTs from 283 LBCL patients treated with commercial CD19 CAR-T at Memorial Sloan Kettering Cancer Center.
Disease sites were categorized as nodal (ND) or extranodal (EN).
EN involvement was common – seen in 76% of patients at baseline.
Patients with exclusive EN disease had outcomes similar to nodal-only cases, but those with both EN + nodal involvement had lower CR rates and shorter PFS – an observation also reported in a parallel publication by Gloria Iacoboni et al.
Before CAR-T, the most commonly involved sites were nodal (≥45% infra- and supradiaphragmatic). EN sites were also frequent – bone/soft tissue (40–45%), GI/peritoneum (22%), and lungs/pleura (18%). Co-involvement patterns were frequent.
Site-specific responses to CAR-T varied widely – highest in bone/soft tissue, supradiaphragmatic nodes, and spleen; lowest in adrenal/GU, lungs/pleura, and CNS. Lungs and GI were also the most relapse-prone sites, with same-site relapse HRs of 7.8 and 6.0.
Among patients who relapsed after CAR-T, outcomes varied by site. Those with nodal-only relapse had 64% 2-year OS, compared to 25% with mixed EN + nodal and 23% with exclusive EN relapse. EN relapse was associated with markedly worse survival.
Our study highlights the need to consider disease location in CAR-T for LBCL. Patients with high-risk EN sites may benefit from tailored strategies – like site-directed radiotherapy – to improve outcomes.
Huge thanks to Memorial Sloan Kettering Biostatistics Service’ Sean Devlin for leading the statistical analyses, and to Alejandro Luna for his tremendous dedication to this work.”
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