Validation of POD24 as a robust early clinical indicator of poor survival in mantle cell lymphoma from 1280 patients on clinical trials, a LYSA study

Abstract In mantle cell lymphoma, early progression of disease has been associated with short overall survival. The impact of clinical, pathological, and treatment strategies on the risk of early relapse has not been assessed in a large cohort of patients. We performed a pooled analysis of patients...

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Main Authors: Clémentine Sarkozy, Loïc Chartier, Vincent Ribrag, Remy Gressin, Christian H. Geisler, Hanneke C. Kluin-Nelemans, Catherine Thieblemont, Franck Morschhauser, François Lemonnier, Violaine Safar, Benoît Tessoulin, Lucie Oberic, Ghandi Damaj, Hervé Ghesquières, Krimo Bouabdallah, René Olivier Casasnovas, Roch Houot, Wolfram Klapper, Barbara Burroni, Christiane Pott, Marie-Hélène Delfau-Larue, Elizabeth Macintyre, Mary Callanan, Mats Jerkeman, Michael Unterhalt, Eva Hoster, Martin Dreyling, Steven Le Gouill, Olivier Hermine, Morgane Cheminant
Format: Article
Language:English
Published: Nature Publishing Group 2025-04-01
Series:Blood Cancer Journal
Online Access:https://doi.org/10.1038/s41408-025-01241-9
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Summary:Abstract In mantle cell lymphoma, early progression of disease has been associated with short overall survival. The impact of clinical, pathological, and treatment strategies on the risk of early relapse has not been assessed in a large cohort of patients. We performed a pooled analysis of patients recruited in France from six randomized first-line MCL trials. Among 1386 treated MCL patients, 1280 were evaluable for POD24 status: 299 (23.4%) with a POD24 event and 981 (76.6%) without. Patients with a POD24 event had a median OS of 9.3 months (95% CI 8.4–11.8) versus not reached (95% CI 97.8–NR) for those without POD24 events. The median post-relapse OS of patients with a late relapse was also significantly longer at 49.4 months (HR = 0.39; 95% CI 0.31–0.48; P < 0.001) as compared to POD24 patients. Baseline variables (age, performance status, B symptoms, LDH/ULN, leukocytes, blastoid variant, and Ki-67 > 30%) were significantly associated with the risk of POD24, independent of ASCT. Among responding patients at end-of-induction (n = 1105) who had received ASCT, anti-CD20 maintenance was associated with a decreased risk of POD24 (OR = 0.37; 95% CI 0.1–1.0). Using this large data set of patients in clinical trials, we confirm that POD24 status is strongly associated with subsequent OS in MCL. Rituximab maintenance provided significant protection against the risk of POD24, independent of ASCT. Progression within 2 years should be considered as a primary endpoint in future studies.
ISSN:2044-5385