Early PET response predicts the risk of relapse after 2L axi-cel in large B-cell lymphoma

Large B-cell lymphoma patients who progress after second-line (2L) CAR T have an increasing number of post-CAR T treatment options available and should be considered for timely intervention if at high risk of CAR T failure. In this national cohort of 302 patients receiving 2L axi-cel, we assessed the use of early FDG PET response to guide post-CAR T management. 245 patients with treatment response at 1-month were grouped according to depth of response by Deauville score (DS): complete metabolic response or focal residual activity in the bridging radiotherapy field (DS1-3/DS4RT), partial response (PR) DS4, and PR DS5. DS response categories were significantly associated with risk of progression, progression-free and overall survival. Patients with DS4 and DS5 response had a 50% and 73% risk of progression by month 6, respectively, compared to 25% for DS1-3/DS4RT (DS4: HR: 3.07 (1.85 - 5.07) and DS5: HR: 5.20 (2.95 - 9.16); p<0.0001), which was independently significant in multivariable analyses. In a risk model using DS categories and pre-infusion LDH levels ≥2ULN, we identified a high-risk group with significant risk of early failure (HR 5.21 (3.27 - 8.29) p<0.001). Our results demonstrate the prognostic value of early PET response in patients treated with 2L axi-cel, independent of pre-infusion risk factors. Responding high-risk patients had ≥70% risk of progression by month 6 and should be strongly considered for early post-CAR T therapies.

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Publication Details

Journal
Blood Advances
Published
2026-03-27
DOI
https://doi.org/10.1182/bloodadvances.2026019802
Primary Topic
Lymphoma Diagnosis and Treatment
Type
article
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article

Early PET response predicts the risk of relapse after 2L axi-cel in large B-cell lymphoma

Francesca Sillito, Rajesh Alajangi, Jane E. Norman, Hwai Jing Hiew et al.
Blood Advances
Lymphoma Diagnosis and Treatment
article

Early PET response predicts the risk of relapse after 2L axi-cel in large B-cell lymphoma

Francesca Sillito, Rajesh Alajangi, Jane E. Norman, Hwai Jing Hiew, George Petrides, Nikesh Chavda, Andrea Kühnl, Emil Kumar, Edward Bataillard, Aikaterini Panopoulou, Wendy Osborne, Ceri Jones, Alison Delaney, Tobias Menne, Sachin Kamat, Ben Uttenthal, Michael Northend, L. Gajendran, Sridhar Chaganti, Amrith Mathew, Nicolas Martinez-Calle, Andrew J Davies, Bernard Douglas Maybury, John G Gribben, William Townsend, Ahmed Abdulgawad, Claire Roddie, Frances Seymour, Amy A Kirkwood, Robin Sanderson
article en

Abstract

Large B-cell lymphoma patients who progress after second-line (2L) CAR T have an increasing number of post-CAR T treatment options available and should be considered for timely intervention if at high risk of CAR T failure. In this national cohort of 302 patients receiving 2L axi-cel, we assessed the use of early FDG PET response to guide post-CAR T management. 245 patients with treatment response at 1-month were grouped according to depth of response by Deauville score (DS): complete metabolic response or focal residual activity in the bridging radiotherapy field (DS1-3/DS4RT), partial response (PR) DS4, and PR DS5. DS response categories were significantly associated with risk of progression, progression-free and overall survival. Patients with DS4 and DS5 response had a 50% and 73% risk of progression by month 6, respectively, compared to 25% for DS1-3/DS4RT (DS4: HR: 3.07 (1.85 - 5.07) and DS5: HR: 5.20 (2.95 - 9.16); p<0.0001), which was independently significant in multivariable analyses. In a risk model using DS categories and pre-infusion LDH levels ≥2ULN, we identified a high-risk group with significant risk of early failure (HR 5.21 (3.27 - 8.29) p<0.001). Our results demonstrate the prognostic value of early PET response in patients treated with 2L axi-cel, independent of pre-infusion risk factors. Responding high-risk patients had ≥70% risk of progression by month 6 and should be strongly considered for early post-CAR T therapies.

Blood Advances
University Hospitals Birmingham NHS Foundation Trust (GB), Nottingham University Hospitals NHS Trust (GB), University College London Hospitals NHS Foundation Trust (GB), Imperial College Healthcare NHS Trust (GB), Queen Elizabeth Hospital Birmingham (GB), University Hospitals Bristol NHS Foundation Trust (GB), University Hospital of Wales (GB), Newcastle upon Tyne Hospitals NHS Foundation Trust (GB), Cambridge University Hospitals NHS Foundation Trust (GB), University Hospital Southampton NHS Foundation Trust (GB), Manchester University NHS Foundation Trust (GB), Sheffield Teaching Hospitals NHS Foundation Trust (GB), King's College Hospital NHS Foundation Trust (GB), St George's Hospital (GB), Royal Marsden Hospital (GB), The Christie NHS Foundation Trust (GB), UCL Biomedical Research Centre (GB), Oxford University Hospitals NHS Trust (GB), King's College Hospital (GB), University of Southampton (GB), University Hospitals Bristol and Weston NHS Foundation Trust (GB), University College London (GB)
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Openalex Percentile: Top 6%
Lymphoma Diagnosis and Treatment
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