A national service for delivering <scp>CD19 CAR‐T</scp>in large B‐cell lymphoma – The <scp>UK</scp> real‐world experience

Kühnl, Andrea; Roddie, Claire; Kirkwood, Amy A.; Tholouli, Eleni; Menne, Tobias; Patel, Amit K.; Besley, Caroline; Chaganti, Sridhar; Sanderson, Robin; O’Reilly, Maeve; Norman, Jane E.; Osborne, Wendy; Bloor, Adrian; Lugthart, Sanne; Malladi, Ram; Patten, Piers; Neill, Lorna; Martínez-Cibrián, Núria; Kennedy, Hannah; Phillips, Elizabeth H; Jones, Ceri; Sharplin, Kirsty; El‐Sharkawi, Dima; Latif, Anne-Louise; Mathew, Amrith; Uttenthal, Ben; Stewart, Orla; Marzolini, Maria A V; Townsend, William; Cwynarski, Kate; Ardeshna, Kirit M.; Ardavan, Arzhang; Robinson, Kate; Pagliuca, Antonio; Collins, Graham P.; Johnson, Roderick J.; McMillan, Andrew

doi:10.1111/bjh.18209

Cited by 50 publications

(59 citation statements)

References 18 publications

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“…Indeed, although we did not assess the time between start of 1 st -line therapy and first relapse/progression, the shorter interval between diagnosis and dosing in the younger cohort suggests a larger fraction of patients with primary/early treatment failure, despite more aggressive induction and also salvage therapy (Supplementary Table S2). Thus, the reason for the difference between the age groups observed here might be that our younger patients obviously represent an extraordinarily unfavorable selection [11], while the outcome of the elderly is comparable to other published realworld experience [4][5][6].…”

Section: To the Editorsupporting

confidence: 70%

“…There have been a few studies suggesting that advanced age is not a major obstacle for CD19-directed CAR-T therapy in r/r LBCL [2][3][4][5], including the recent large post-authorization safety study conducted by the CIBMTR for axi-cel [6]. In the latter, ORR and PFS tended to be better in 484 patients aged 65 or higher compared to 813 younger patients on multivariate analysis, despite significantly higher risks of overall and grade ≥3 CRS and neurotoxocity, respectively, in the elderly [6].…”

Section: To the Editormentioning

confidence: 99%

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Impact of age on outcome of CAR-T cell therapies for large B-cell lymphoma: the GLA/DRST experience

Dreger¹,

Subklewe²,

Tresckow³

et al. 2022

Bone Marrow Transplant

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Bone Marrow Transplantationyears or older, this finding contradicts current perceptions considering tisa-cel as the preferred choice for older patients because of its better tolerability [1] and, thus, might have impact on clinical practice.Of note, detrimental age effects did not emerge in our series even when the elderly group was further sub-categorized, implying that a meaningful upper age limit for CD19 CARTs in this indication could not be defined.This study is limited by sample size, its retrospective character with inherent selection bias, and the fact that it is a post-hoc analysis. Nevertheless, its results suggest that increasing age per se is not a risk factor for outcome of CD19 CAR-T-cell therapy in LBCL, and a strict upper age limit for this type of treatment does not exist. Finally, despite higher NRM, PFS tended to be better with axi-cel compared to tisa-cel also in the elderly, suggesting that tisa-cel is not the obligatory choice for this subset including selected patients aged 75 years or older.

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Section: To the Editorsupporting

confidence: 70%

Section: To the Editormentioning

confidence: 99%

Impact of age on outcome of CAR-T cell therapies for large B-cell lymphoma: the GLA/DRST experience

Dreger¹,

Subklewe²,

Tresckow³

et al. 2022

Bone Marrow Transplant

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“…In a real‐world dataset ( n = 33), low‐risk smIPI score was associated with a superior PFS 5 . In high‐grade B‐cell non‐Hodgkin lymphoma markers of disease activity (i.e., bulk, LDH), 3+ extranodal sites and inferior ECOG PS correlate with inferior survival and immediate CAR T‐related toxicity post‐infusion 12–15 . Extrapolating this experience to MCL, adequate disease control pre‐CAR T infusion may be critical to improve the drop‐out rate but also to optimise the chances of durable remission and improve tolerability of Tecartus.…”

Section: Nhs England Nccp Eligibility Criteria Commentsmentioning

confidence: 94%

Addendum to British Society for Haematology Guideline for the management of mantle cell lymphoma, 2018 (Br. J. Haematol. 2018; 182: 46–62): Risk assessment of potential CAR T candidates receiving a covalent Bruton tyrosine kinase inhibitor for relapsed/refractory disease

et al. 2022

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“…A wide spectrum of patients are referred for CAR-T therapy, but a significant proportion are frail. Patients are often heavily pre-treated and chemotherapy-resistant, with a high disease burden, as evidenced by high lactate dehydrogenase and poor performance scores [17,18]. Given this patient profile, supportive care measures to protect patients from potential CAR-T complications are paramount.…”

Section: Introductionmentioning

confidence: 99%

Supportive care for chimeric antigen receptor T-cell patients

Springell

O’Reilly

Roddie

2023

Current Opinion in Supportive &Amp; Palliative Care

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Purpose of review The purpose of this review is to provide clear guidance to health professionals delivering chimeric antigen receptor T-cell (CAR-T) therapy on the best supportive management throughout the CAR-T pathway, from referral to long-term follow-up, including psychosocial aspects. Recent findings CAR-T therapy has changed the treatment landscape for relapsed/refractory (r/r) B-cell malignancy. Approximately 40% of r/r B-cell leukaemia/lymphoma patients receiving CD19-targeted CAR-T therapy achieve durable remission following a single dose. The field is rapidly expanding to encompass new CAR-T products for indications such as multiple myeloma, mantle cell lymphoma and follicular lymphoma, and the number of patients eligible to receive CAR-T therapy is likely to continue to grow exponentially. CAR-T therapy is logistically challenging to deliver, with involvement of many stakeholders. In many cases, CAR-T therapy requires an extended inpatient hospital admission, particularly in older, comorbid patients, and is associated with potentially severe immune side effects. Further, CAR-T therapy can lead to protracted cytopenias that can last for several months accompanied by a susceptibility to infection. Summary For the reasons listed above, standardised, comprehensive supportive care is critically important to ensure that CAR-T therapy is delivered as safely as possible and that patients are fully informed of the risks and benefits, as well as the requirement for extended hospital admission and follow-up, to fully realise the potential of this transformative treatment modality.

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A national service for delivering CD19 CAR‐Tin large B‐cell lymphoma – The UK real‐world experience

Abstract: CD19 CAR-T have emerged as a new standard treatment for relapsed/refractory (r/r) large B-cell lymphoma (LBCL). CAR-T real-world (RW) outcomes published to date suggest significant variability across countries. We provide results of a large national | 493 KUHNL et al.

Cited by 50 publications

References 18 publications

Impact of age on outcome of CAR-T cell therapies for large B-cell lymphoma: the GLA/DRST experience

Impact of age on outcome of CAR-T cell therapies for large B-cell lymphoma: the GLA/DRST experience

Addendum to British Society for Haematology Guideline for the management of mantle cell lymphoma, 2018 (Br. J. Haematol. 2018; 182: 46–62): Risk assessment of potential CAR T candidates receiving a covalent Bruton tyrosine kinase inhibitor for relapsed/refractory disease

Supportive care for chimeric antigen receptor T-cell patients

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