Roddie, Claire; Neill, Lorna; Osborne, Wendy; Iyengar, Sunil; Tholouli, Eleni; Irvine, David; Chaganti, Sridhar; ... Kuhnl, Andrea; + view all Roddie, Claire; Neill, Lorna; Osborne, Wendy; Iyengar, Sunil; Tholouli, Eleni; Irvine, David; Chaganti, Sridhar; Besley, Caroline; Bloor, Adrian Jc; Jones, Ceri H; Uttenthal, Ben J; Johnson, Roderick J; Sanderson, Robin; Cheok, Kathleen Pl; Marzolini, Maria AV; Townsend, William M; O'Reilly, Maeve; Kirkwood, Amy A; Kuhnl, Andrea; - view fewer (2023) Effective bridging therapy can improve CD19 CAR-T outcomes while maintaining safety in patients with large B-cell lymphoma. Blood Advances , 7 (12) pp. 2872-2883. 10.1182/bloodadvances.2022009019.

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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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