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Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma
Roddie, C. Neill, L. Osborne, W. Iyengar, S. Tholouli, E. Irvine, D. Chaganti, S. Besley, C. Bloor, Adrian Jones, C. H.
Roddie, C.
Neill, L.
Osborne, W.
Iyengar, S.
Tholouli, E.
Irvine, D.
Chaganti, S.
Besley, C.
Bloor, Adrian
Jones, C. H.
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Abstract
The impact of bridging therapy (BT) on CD19-directed chimeric antigen receptor T-cell (CD19CAR-T) outcomes in large B-cell lymphoma (LBCL) is poorly characterised. Current practice is guided by physician preference rather than established evidence. Identification of effective BT modalities and factors predictive of response could improve CAR-T intention to treat and clinical outcomes. We assessed BT modality and response in 375 adult LBCL patients in relation to outcomes following axicabtagene ciloleucel (Axi-cel) or tisagenlecleucel (Tisa-cel). The majority of patients received BT with chemotherapy (57%) or radiotherapy (17%). We observed that BT was safe for patients, with minimal morbidity/mortality. We showed that complete or partial response to BT conferred a 42% reduction in disease progression and death following CD19CAR-T therapy. Multivariate analysis identified several factors associated with likelihood of response to BT, including response to last line therapy, the absence of bulky disease, and the use of Polatuzumab-containing chemotherapy regimens. Our data suggested that complete/partial response to BT may be more important for Tisa-cel than Axi-cel, as all Tisa-cel patients with less than partial response to BT experienced frank relapse within 12 months of CD19CAR-T infusion. In summary, BT in LBCL should be carefully planned towards optimal response and disease debulking, to improve CD19CAR-T patient outcomes. Polatuzumab-containing regimens should be strongly considered for all suitable patients, and failure to achieve complete/partial response to BT pre-Tisa-cel may prompt consideration of further lines of BT where possible.
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2023
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Roddie C, Neill L, Osborne W, Iyengar S, Tholouli E, Irvine D, et al. Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma. Blood advances. 2023 Feb 1. PubMed PMID: 36724512. Epub 2023/02/02. eng.