Outcome and feasibility of radiotherapy bridging in large B-cell lymphoma patients receiving CD19 CAR T in the UK.
cellular therapies
lymphoid malignancies
radiotherapy
Journal
British journal of haematology
ISSN: 1365-2141
Titre abrégé: Br J Haematol
Pays: England
ID NLM: 0372544
Informations de publication
Date de publication:
09 Apr 2024
09 Apr 2024
Historique:
revised:
07
03
2024
received:
06
02
2024
accepted:
27
03
2024
medline:
10
4
2024
pubmed:
10
4
2024
entrez:
10
4
2024
Statut:
aheadofprint
Résumé
Radiotherapy (RT) has potential synergistic effects with chimeric antigen receptor (CAR) T but is not widely used as bridging therapy due to logistical challenges and lack of standardised protocols. We analysed RT bridging in a multicentre national cohort of large B-cell lymphoma patients approved for 3L axicabtagene ciloleucel or tisagenlecleucel across 12 UK centres. Of 763 approved patients, 722 were leukapheresed, 717 had data available on bridging therapy. 169/717 (24%) received RT bridging, 129 as single modality and 40 as combined modality treatment (CMT). Of 169 patients, 65.7% had advanced stage, 36.9% bulky disease, 86.5% elevated LDH, 41.7% international prognostic index (IPI) ≥3 and 15.2% double/triple hit at the time of approval. Use of RT bridging varied from 11% to 32% between centres and increased over time. Vein-to-vein time and infusion rate did not differ between bridging modalities. RT-bridged patients had favourable outcomes with 1-year progression-free survival (PFS) of 56% for single modality and 47% for CMT (1-year PFS 43% for systemic bridging). This is the largest cohort of LBCL patients receiving RT bridging prior to CAR T reported to date. Our results show that RT bridging can be safely and effectively used even in advanced stage and high-risk disease, with low dropout rates and excellent outcomes.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024 British Society for Haematology and John Wiley & Sons Ltd.
Références
Neelapu SS, Locke FL, Bartlett NL, Lekakis LJ, Miklos DB, Jacobson CA, et al. Axicabtagene ciloleucel CAR T‐cell therapy in refractory large B‐cell lymphoma. N Engl J Med. 2017;377:2531–2544.
Schuster SJ, Bishop MR, Tam CS, Waller EK, Borchmann P, McGuirk JP, et al. Tisagenlecleucel in adult relapsed or refractory DLBCL. N Engl J Med. 2019;380:45–56.
Bethge WA, Martus P, Schmitt M, Holtick U, Subklewe M, von Tresckow B, et al. GLA/DRST real‐world outcome analysis of CAR‐T cell therapies for large B‐cell lymphoma in Germany. Blood. 2022;140:349–358. https://doi.org/10.1182/blood.2021015209
Kwon M, Iacoboni G, Reguera JL, Corral LL, Morales RH, Ortiz‐Maldonado V, et al. Axicabtagene ciloleucel compared to tisagenlecleucel for the treatment of aggressive B‐cell lymphoma. Haematologica. 2023;108:110–121.
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 Adv. 2023;7:2872–2883. https://doi.org/10.1182/bloodadvances.2022009019
Chavez JC, Jain MD, Kharfan‐Dabaja MA. Cytokine release syndrome and neurologic toxicities associated with chimeric antigen receptor T‐cell therapy: a comprehensive review of emerging grading models. Hematol Oncol Stem Cell Ther. 2020;13:1–6.
Wudhikarn K, Palomba ML, Pennisi M, Garcia‐Recio M, Flynn JR, Devlin SM, et al. Infection during the first year in patients treated with CD19 CAR T cells for diffuse large B cell lymphoma. Blood Cancer J. 2020;10:79.
Kuhnl A, Roddie C, Kirkwood AA, Tholouli E, Menne T, Patel A, et al. A national service for delivering CD19 CAR‐tin large B‐cell lymphoma – the UK real‐world experience. Br J Haematol. 2022;198:492–502. https://doi.org/10.1111/bjh.18209
Rejeski K, Perez A, Sesques P, Hoster E, Berger C, Jentzsch L, et al. CAR‐HEMATOTOX: a model for CAR T‐cell related hematological toxicity in relapsed/refractory large B‐cell lymphoma. Blood. 2021;138:2499–2513. https://doi.org/10.1182/blood.2020010543
Figura NB, Robinson TJ, Sim AJ, Wang X, Cao B, Chavez JC, et al. Patterns and predictors of failure in recurrent or refractory large B‐cell lymphomas after chimeric antigen receptor T‐cell therapy. Int J Radiat Oncol Biol Phys. 2021;111:1145–1154.
Saifi O, Breen WG, Lester SC, Rule WG, Stish B, Rosenthal A, et al. Does bridging radiation therapy affect the pattern of failure after CAR T‐cell therapy in non‐Hodgkin lymphoma? Radiother Oncol. 2022;166:171–179.
Hubbeling H, Silverman EA, Michaud L, Tomas AA, Shouval R, Flynn J, et al. Bridging radiation rapidly and effectively cytoreduces high‐risk relapsed/refractory aggressive B cell lymphomas prior to chimeric antigen receptor T cell therapy. Transplant Cell Ther. 2023;29:259.e1–259.e10. https://doi.org/10.1016/j.jtct.2022.12.021
Deselm C. The current and future role of radiation therapy in the era of CAR T‐cell salvage. Br J Radiol. 2021;94:20210098.
Sim AJ, Jain MD, Figura NB, Chavez JC, Shah BD, Khimani F, et al. Radiation therapy as a bridging strategy for CAR T cell therapy with axicabtagene ciloleucel in diffuse large B‐cell lymphoma. Int J Radiat Oncol Biol Phys. 2019;105:1012–1021. https://doi.org/10.1016/j.ijrobp.2019.05.065
Pinnix CC, Gunther JR, Dabaja BS, Strati P, Fang P, Hawkins MC, et al. Bridging therapy prior to axicabtagene ciloleucel for relapsed/refractory large B‐cell lymphoma. Blood Adv. 2020;4:2871–2883. https://doi.org/10.1182/bloodadvances.2020001837
Cheson BD, Fisher RI, Barrington SF, Cavalli F, Schwartz LH, Zucca E, et al. Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non‐Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014;32:3059–3067.
Bachy E, le Gouill S, di Blasi R, Sesques P, Manson G, Cartron G, et al. A real‐world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma. Nat Med. 2022;28:2145–2154.
Vercellino L, di Blasi R, Kanoun S, Tessoulin B, Rossi C, D'Aveni‐Piney M, et al. Predictive factors of early progression after CAR T‐cell therapy in relapsed/refractory diffuse large B‐cell lymphoma. Blood Adv. 2020;4:5607–5615.
Kuhnl A, Roddie C, Kirkwood AA, Menne T, Cuadrado M, Marzolini MAV, et al. Early FDG‐PET response predicts CAR‐T failure in large B‐cell lymphoma. Blood Adv. 2022;6:321–326.
Imber BS, Silverman EA, Leithner D, Hubbeling H, Shah GL, Fregonese B, et al. Dynamics of radiomic features following bridging therapy determine CD19 chimeric antigen receptor (car) T‐cell therapy outcome. Hematol Oncol. 2023;41:93–94.
DeSelm C, Palomba ML, Yahalom J, Hamieh M, Eyquem J, Rajasekhar VK, et al. Low‐dose radiation conditioning enables CAR T cells to mitigate antigen escape. Mol Ther. 2018;26:2542–2552.
Kim AB, Chou SY, Kang S, Kwon E, Inkman M, Szymanski J, et al. Intrinsic tumor resistance to CAR T cells is a dynamic transcriptional state that is exploitable with low‐dose radiation. Blood Adv. 2023;7:5396–5408. https://doi.org/10.1182/bloodadvances.2022009543
Ladbury C, Dandapani S, Hao C, Fabros M, Amini A, Sampath S, et al. Long‐term follow‐up of bridging therapies prior to CAR T‐cell therapy for relapsed/refractory large B cell lymphoma. Cancers (Basel). 2023;15:1747.