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...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| 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 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850172955127971840 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Clémentine Sarkozy |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-ea0d1c5bbe034d26a8e1721a0b4dbedb |
| institution | OA Journals |
| issn | 2044-5385 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Blood Cancer Journal |
| spelling | doaj-art-ea0d1c5bbe034d26a8e1721a0b4dbedb2025-08-20T02:19:57ZengNature Publishing GroupBlood Cancer Journal2044-53852025-04-011511710.1038/s41408-025-01241-9Validation of POD24 as a robust early clinical indicator of poor survival in mantle cell lymphoma from 1280 patients on clinical trials, a LYSA studyClémentine Sarkozy0Loïc Chartier1Vincent Ribrag2Remy Gressin3Christian H. Geisler4Hanneke C. Kluin-Nelemans5Catherine Thieblemont6Franck Morschhauser7François Lemonnier8Violaine Safar9Benoît Tessoulin10Lucie Oberic11Ghandi Damaj12Hervé Ghesquières13Krimo Bouabdallah14René Olivier Casasnovas15Roch Houot16Wolfram Klapper17Barbara Burroni18Christiane Pott19Marie-Hélène Delfau-Larue20Elizabeth Macintyre21Mary Callanan22Mats Jerkeman23Michael Unterhalt24Eva Hoster25Martin Dreyling26Steven Le Gouill27Olivier Hermine28Morgane Cheminant29Hematology Departement, Institut Curie, Saint Cloud, Université de Versailles Saint-Quentin (UVSQ)Statistiques, Lymphoma Academic Research Organisation (LYSA)Haematology Department, Institut Gustave RoussyHaematology Department, Univ. Grenoble Alpes. University Hospital, Grenoble France & Institute For Advanced Biosciences (INSERM U1209)Haematology Department, Rigshospitalet, Copenhagen University HospitalHaematology Department, University Medical Center Groningen, University of GroningenUniversité Paris Cité, Inserm U1153Univ. Lille, CHU Lille, ULR 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies AssociéesHaematology Department, Groupe Hospitalier Mondor, Assistance Publique Hôpitaux de ParisHaematology Department, Centre hospitalier Lyon Sud - 145 Chemin du Grand RevoyetHaematology Department, Nantes University HospitalHaematology Department, Institut universitaire du cancer Toulouse- OncopoleHaematology Department, Normandie University, Hematology InstituteHaematology Department, Centre hospitalier Lyon Sud - 145 Chemin du Grand RevoyetHaematology Department, Centre Hospitalier Universitaire de BordeauxHaematology Department, Centre Hospitalier Universitaire Dijon, INSERM UMR1231Department of Hematology, University Hospital of Rennes, UMR U1236, INSERM, University of Rennes, French Blood EstablishmentInstitut für Pathologie, Sektion Hämatopathologie und Lymphknotenregister, University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University KielDepartment of Pathology, Cochin University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP)University Hospital Schleswig-Holstein Campus Kiel/Christian-Albrechts University KielBiological Haematology and Immunology Department, Groupe Hospitalier Mondor, Assistance Publique Hôpitaux de Paris, INSERM U955Biological Haematology Department, Necker-Enfants malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP)University of Burgundy-INSERM 1231-CHU DijonDepartment of Oncology, Institute of Clinical Sciences, Lund University and Skane University Hospital SE22185Department of Medicine III, LMU University HospitalInstitute for Medical Information Processing, Biometry, and Epidemiology, LMU MunichDepartment of Medicine III, LMU University HospitalHematology Departement, Institut Curie, Saint Cloud, Université de Versailles Saint-Quentin (UVSQ)Haematology Department, Necker-Enfants malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP)Haematology Department, Necker-Enfants malades University Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP)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.https://doi.org/10.1038/s41408-025-01241-9 |
| spellingShingle | 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 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 Blood Cancer Journal |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://doi.org/10.1038/s41408-025-01241-9 |
| work_keys_str_mv | AT clementinesarkozy validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT loicchartier validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT vincentribrag validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT remygressin validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT christianhgeisler validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT hannekeckluinnelemans validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT catherinethieblemont validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT franckmorschhauser validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT francoislemonnier validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT violainesafar validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT benoittessoulin validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT lucieoberic validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT ghandidamaj validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT herveghesquieres validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT krimobouabdallah validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT reneoliviercasasnovas validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT rochhouot validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT wolframklapper validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT barbaraburroni validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT christianepott validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT mariehelenedelfaularue validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT elizabethmacintyre validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT marycallanan validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT matsjerkeman validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT michaelunterhalt validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT evahoster validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT martindreyling validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT stevenlegouill validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT olivierhermine validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy AT morganecheminant validationofpod24asarobustearlyclinicalindicatorofpoorsurvivalinmantlecelllymphomafrom1280patientsonclinicaltrialsalysastudy |