50 results on '"Gastinne, T"'
Search Results
2. AXICABTAGENE CILOLEUCEL AS SECOND‐LINE THERAPY FOR LARGE B‐CELL LYMPHOMA IN TRANSPLANT‐INELIGIBLE PATIENTS: FINAL ANALYSIS OF ALYCANTE, A PHASE 2 LYSA STUDY
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Houot, R., primary, Bachy, E., additional, Cartron, G., additional, Gros, F., additional, Morschhauser, F., additional, Oberic, L., additional, Gastinne, T., additional, Feugier, P., additional, Dulery, R., additional, Thieblemont, C., additional, Joris, M., additional, Jardin, F., additional, Choquet, S., additional, Casasnovas, O., additional, Brisou, G., additional, Cheminant, M., additional, Bay, J., additional, Gutierrez, F. Llamas, additional, Menard, C., additional, Tarte, K., additional, Delfau, M., additional, Itti, E., additional, Bailly, C., additional, Al Tabaa, Y., additional, Laurent, C., additional, and Lemonnier, F., additional
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- 2023
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3. Prognostic value of TARC and quantitative PET parameters in relapsed or refractory Hodgkin lymphoma patients treated with brentuximab vedotin and DHAP
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Driessen, J., Kersten, M. J., Visser, L., van den Berg, A., Tonino, S. H., Zijlstra, J. M., Lugtenburg, P. J., Morschhauser, Franck, Hutchings, M., Amorim, S., Gastinne, T., Nijland, M., Zwezerijnen, G. J. C., Boellaard, R., de Vet, H. C. W., Arens, A. I. J., Valkema, R., Liu, R. D. K., Drees, E. E. E., de Jong, D., Plattel, W. J., Diepstra, A., Groupe de Recherche sur les formes Injectables et les Technologies Associées - ULR 7365 (GRITA), Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Graduate School, CCA - Cancer Treatment and Quality of Life, Clinical Haematology, CCA - Imaging and biomarkers, Stem Cell Aging Leukemia and Lymphoma (SALL), Translational Immunology Groningen (TRIGR), Hematology, Radiology & Nuclear Medicine, CCA - Cancer Treatment and quality of life, Radiology and nuclear medicine, Amsterdam Neuroscience - Brain Imaging, Epidemiology and Data Science, APH - Methodology, and Pathology
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Brentuximab Vedotin ,Cancer Research ,Immunoconjugates ,[SDV]Life Sciences [q-bio] ,Hematology ,Prognosis ,Hodgkin Disease ,Oncology ,SDG 3 - Good Health and Well-being ,Positron-Emission Tomography ,Humans ,Prospective Studies ,Neoplasm Recurrence, Local ,Vitamin D ,Rare cancers Radboud Institute for Health Sciences [Radboudumc 9] ,Stem Cell Transplantation - Abstract
Contains fulltext : 287833.pdf (Publisher’s version ) (Closed access) Risk-stratified treatment strategies have the potential to increase survival and lower toxicity in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients. This study investigated the prognostic value of serum (s)TARC, vitamin D and lactate dehydrogenase (LDH), TARC immunohistochemistry and quantitative PET parameters in 65 R/R cHL patients who were treated with brentuximab vedotin (BV) and DHAP followed by autologous stem-cell transplantation (ASCT) within the Transplant BRaVE study (NCT02280993). At a median follow-up of 40 months, the 3-year progression free survival (PFS) was 77% (95% CI: 67-88%) and the overall survival was 95% (90-100%). Significant adverse prognostic markers for progression were weak/negative TARC staining of Hodgkin Reed-Sternberg cells in the baseline biopsy, and a high standard uptake value (SUV)mean or SUVpeak on the baseline PET scan. After one cycle of BV-DHAP, sTARC levels were strongly associated with the risk of progression using a cutoff of 500 pg/ml. On the pre-ASCT PET scan, SUVpeak was highly prognostic for progression post-ASCT. Vitamin D, LDH and metabolic tumor volume had low prognostic value. In conclusion, we established the prognostic impact of sTARC, TARC staining, and quantitative PET parameters for R/R cHL, allowing the use of these parameters in prospective risk-stratified clinical trials. Trial registration: NCT02280993.
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- 2022
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4. Preliminary Clinical Data From Ongoing Phase 2 Study With Enhancer of Zeste Homolog 2 (EZH2) Inhibitor CPI-0209 in Patients With Advanced Solid Tumors or Hematologic Malignancies
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Kindler, H., primary, Harvey, R.D., additional, Duska, L.R., additional, Gandhi, L., additional, Sullivan, R.J., additional, Gastinne, T., additional, Kwiatek, M., additional, García-Sancho, A.M., additional, Hadar, N., additional, Kann, L., additional, Faulhaber, N., additional, and Drescher, C., additional
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- 2022
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5. S210: CAR T-CELLS ASSOCIATED ACUTE TOXICITY IN B-CELL NON-HODGKIN LYMPHOMA: REAL-WORLD STUDY FROM THE DESCAR-T REGISTRY
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SESQUES, P., primary, DI BLASI, R., additional, LE GOUILL, S., additional, CARTRON, G., additional, MANSON, G., additional, BEAUVAIS, D., additional, LE BRAS, F., additional, GROS, F. X., additional, CHOQUET, S., additional, BORIES, P., additional, RUBIO, M. T., additional, CASASNOVAS, R. O., additional, BOUNAIX, L., additional, MOHTY, M., additional, JORIS, M., additional, ABRAHAM, J., additional, CASTILLA LLORENTE, C., additional, LOSCHI, M., additional, CARRAS, S., additional, CHAUCHET, A., additional, DRIEU LA ROCHELLE, L., additional, ZERBIT, J., additional, HERMINE, O., additional, GUIDEZ, S., additional, GASTINNE, T., additional, TUDESQ, J. J., additional, FOGARTY, P., additional, BROUSSAIS, F., additional, MORSCHHAUSER, F., additional, HOUOT, R., additional, THIEBLEMONT, C., additional, and BACHY, E., additional
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- 2022
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6. P1133: SUB-CUTANEOUS RITUXIMAB INDUCTION FOLLOWED BY SHORT RITUXIMAB MAINTENANCE IMPROVES PFS IN PATIENTS WITH LOW-TUMOR BURDEN FOLLICULAR LYMPHOMA. FINAL RESULTS OF FLIRT PHASE III TRIAL, A LYSA STUDY.
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Cartron, G., primary, Bachy, E., additional, Tilly, H., additional, Daguindau, N., additional, Pica, G.-M., additional, Bijou, F., additional, Mounier, C., additional, Clavert, A. M., additional, Damaj, G. L., additional, Slama, B., additional, Casasnovas, O., additional, Houot, R., additional, Bouabdallah, K., additional, Sibon, D., additional, Fitoussi, O., additional, Morineau, N., additional, Herbaux, C., additional, Gastinne, T., additional, Fornecker, L.-M., additional, Haioun, C., additional, Launay, V., additional, Araujo, C., additional, Benbrahim, O., additional, Sanhes, L., additional, Gressin, R., additional, Gonzalez, H., additional, Morschhauser, F., additional, Xerri, L., additional, Tarte, K., additional, and Pranger, D., additional
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- 2022
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7. S260: A MATCHED COMPARISON OF TISAGENLECLEUCEL AND AXICABTAGENE CILOLEUCEL CAR T CELLS IN RELAPSED OR REFRACTORY DIFFUSE LARGE B-CELL LYMPHOMA: A REAL-LIFE LYSA STUDY FROM THE FRENCH DESCAR-T REGISTRY
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Bachy, E., primary, Le Gouill, S., additional, Sesques, P., additional, Di Blasi, R., additional, Guillaume, M., additional, Cartron, G., additional, Beauvais, D., additional, Roulin, L., additional, Gros, F. X., additional, Rubio, M. T., additional, Bories, P., additional, Bay, J. O., additional, Castilla Llorente, C., additional, Choquet, S., additional, Casasnovas, R.-O., additional, Mothy, M., additional, Guidez, S., additional, Joris, M., additional, Loschi, M., additional, Carras, S., additional, Abraham, J., additional, Chauchet, A., additional, Drieu La Rochelle, L., additional, Zerbit, J., additional, Hermine, O., additional, Gastinne, T., additional, Tudesq, J. J., additional, Gat, E., additional, Broussais, F., additional, Thieblemont, C., additional, Houot, R., additional, and Morschhauser, F., additional
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- 2022
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8. Transfusion needs after CD19 CAR T‐cells for large B‐cell lymphoma: predictive factors and impact on outcome. A DESCAR‐T study.
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Vic, S., Thibert, J., Bachy, E., Cartron, G., Gastinne, T., Morschhauser, F., Le Bras, F., Bouabdallah, K., Despas, F., Bay, J., Rubio, M., Mohty, M., Casasnovas, O., Choquet, S., Castilla‐Llorente, C., Guidez, S., Loschi, M., Guffroy, B., Carras, S., and La Rochelle, L. Drieu
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T cells ,CD19 antigen ,ERYTHROCYTES ,LYMPHOMAS ,CYTOKINE release syndrome - Abstract
Transfusion needs may impact patients' quality of life and CAR T-cells efficacy through transfusion-related immunomodulation. Transfusion needs after CD19 CAR T-cells for large B-cell lymphoma: predictive factors and impact on outcome. B Introduction: b Patients undergoing CAR T-cell therapy may experience severe cytopenias due to lymphodepleting chemotherapy and/or CAR T-cells. [Extracted from the article]
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- 2023
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9. EARLY CTDNA CLEARANCE AFTER CAR T‐CELL INFUSION PREDICTS OUTCOME IN PATIENTS WITH LARGE B‐CELL LYMPHOMA : RESULTS FROM ALYCANTE, A PHASE 2 LYSA STUDY.
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Delfau‐Larue, M., Viailly, P., Cartron, G., Morschhauser, F., Gros, F., Gastinne, T., Oberic, L., Bachy, E., Dulery, R., Feugier, P., Menard, C., Quelen, C., Pangault, C., Portugues, C., Gomes, L., Itti, E., Bailly, C., Lemonnier, F., Laurent, C., and Houot, R.
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CIRCULATING tumor DNA ,T cells ,LYMPHOMAS - Abstract
EARLY CTDNA CLEARANCE AFTER CAR T-CELL INFUSION PREDICTS OUTCOME IN PATIENTS WITH LARGE B-CELL LYMPHOMA: RESULTS FROM ALYCANTE, A PHASE 2 LYSA STUDY B Introduction: b CAR T-cells have significantly improved the outcome of patients with relapsed or refractory ( I R i / I R i ) large B-cell lymphoma (LBCL). The aim of our study was to monitor ctDNA before and after CAR T-cell infusion and correlate the results with clinical outcome in the ALYCANTE trial. [Extracted from the article]
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- 2023
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10. 89 (PB079) - Preliminary Clinical Data From Ongoing Phase 2 Study With Enhancer of Zeste Homolog 2 (EZH2) Inhibitor CPI-0209 in Patients With Advanced Solid Tumors or Hematologic Malignancies
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Kindler, H., Harvey, R.D., Duska, L.R., Gandhi, L., Sullivan, R.J., Gastinne, T., Kwiatek, M., García-Sancho, A.M., Hadar, N., Kann, L., Faulhaber, N., and Drescher, C.
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- 2022
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11. NATHALI‐01: A PHASE 1/2A TRIAL OF UCART20X22, AN ALLOGENEIC DUAL CAR T‐CELL THERAPY FOR PATIENTS WITH RELAPSED/REFRACTORY B‐CELL NON‐HODGKIN LYMPHOMA (NHL).
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Bachy, E., Ramakrishnan, A., Thieblemont, C., Alfonso, A., Braunschweig, I., Riedell, P. A., Cartron, G., Barba, P., Gastinne, T., Simon, J. A. Perez, Solano, C., Meadows, S., LaCroce, A., Thomas, D., Poirot, C., Newhall, K. J., Lee, D. J., Frattini, M. G., and Abramson, J.
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CD19 antigen ,NON-Hodgkin's lymphoma ,T cells ,CD20 antigen ,STOCK ownership ,CHIMERIC antigen receptors - Abstract
Eligibility criteria include age 18-80y, lymphoma cell expression of either or both CD20 and CD22, and >= 2 prior treatment regimens including autologous CD19 CAR T-cell therapy if eligible. NATHALI-01: A PHASE 1/2A TRIAL OF UCART20X22, AN ALLOGENEIC DUAL CAR T-CELL THERAPY FOR PATIENTS WITH RELAPSED/REFRACTORY B-CELL NON-HODGKIN LYMPHOMA (NHL) B Introduction: b Autologous CAR T-cell therapies have been transformative in the treatment of selected blood cancers. [Extracted from the article]
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- 2023
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12. KILT: A RANDOMIZED NON‐COMPARATIVE PHASE II LYSA STUDY OF LACUTAMAB WITH GEMOX VERSUS GEMOX IN RELAPSED/REFRACTORY PERIPHERAL T‐CELL LYMPHOMA.
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Cheminant, M., Carras, S., Bruneau, J., Lemonnier, F., Bachy, E., Herbaux, C., Feugier, P., Daguindau, N., Gastinne, T., Guillermin, Y., Lamarque, M., Slama, B., Wolfromm, A., Morschhauser, F., Tournilhac, O., Gaulard, P., Asnafi, V., Ortonne, N., Damaj, G., and Hermine, O.
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T-cell lymphoma ,KILLER cells - Abstract
KILT: A RANDOMIZED NON-COMPARATIVE PHASE II LYSA STUDY OF LACUTAMAB WITH GEMOX VERSUS GEMOX IN RELAPSED/REFRACTORY PERIPHERAL T-CELL LYMPHOMA B Background: b Peripheral T-cell Lymphoma (PTCL) is a heterogeneous group of mature T-cell lymphomas (TCL) with adverse outcomes. KIR3DL2 is a killer immunoglobulin-like receptor that is expressed across different subtypes of TCL, including approximately 40% of PTCL. [Extracted from the article]
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- 2023
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13. REALMA: Subset of patients with Marginal Zone Lymphomas from the French nationwide REALYSA real‐world prospective cohort.
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Bommier, C., Donzel, M., Rossi, C., Fornecker, L., Bijou, F., Chauchet, A., Lebras, L., Ysebaert, L., Haioun, C., Bouabdallah, K., Morineau, N., Gastinne, T., Amorim, S., Jardin, F., Abraham, J., Lamy de la Chapelle, T., Gressin, R., Fouillet, L., Fruchart, C., and Morschhauser, F.
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LYMPHOMAS ,NON-Hodgkin's lymphoma - Abstract
Regarding the B initial workup b , while at least one imagery was offered in 97% of patients, SP 18 sp FDG-PET/CT (EMZL 78%, SMZL 62%, NMZL 78%) was performed more frequently than CT-scan at baseline (EMZL 73%, SMZL 62%, NMZL 71%), although 47% patients underwent both procedures. Diagnosis of MZL was mostly evoked by general practitioners (48%) but patients were finally treated by hematologists (98%). B Background: b Marginal Zone Lymphomas (MZL) are a heterogeneous group of lymphomas that include three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). [Extracted from the article]
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- 2023
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14. Classic Hodgkin Lymphoma: The LYSA pragmatic guidelines.
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Rossi C, Manson G, Marouf A, Cabannes-Hamy A, Nicolas-Virelizier E, Maerevoet M, Alcantara M, Molina L, Ceraulo A, Poirée M, Galtier J, Diop N, Delette C, Segot A, Dubois S, Waultier A, Bernard S, Noël R, Guidez S, Kohn M, Bailly S, Moatti H, Touati M, Renaud L, Kanoun S, Cottereau AS, Kirova Y, Peignaux K, Dourthe ME, Simonin M, Leblanc T, Quéro L, Krzisch D, Duléry R, Grenier A, Gastinne T, Casasnovas O, Gallamini A, André M, Morschhauser F, Deau B, Fornecker LM, and Ghesquières H
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- Humans, Practice Guidelines as Topic, Hodgkin Disease pathology, Hodgkin Disease therapy, Hodgkin Disease diagnosis
- Abstract
Classic Hodgkin lymphoma (HL) is a distinct entity among hematological malignancies of B-cell origin. It is characterized by its unique histopathological features and generally favorable prognosis. Over the years, advancements in understanding its pathogenesis, coupled with refined diagnostic and evaluation modalities, as well as therapeutic strategies, have significantly transformed the landscape of HL management. In this article, we present a comprehensive set of recommendations for the management of HL, encompassing various aspects of diagnosis, risk stratification, evaluation, and treatment. These recommendations are based on the latest evidence-based guidelines, expert consensus opinions, and clinical trial data, aiming to provide clinicians with a practical framework for delivering optimal care to patients with HL., Competing Interests: Declaration of Competing Interest CR has received a research grant from Roche and personal fees and non-financial support from Janssen, Roche, Takeda, and Abbvie. ROC has received a research grant from Gilead and Takeda and personal fees and non-financial support from Janssen, Roche, Takeda, Merck/BMS, Abbvie, and Amgen. The other authors declare no competing interests. MA performed scientific and medical consul/ng for Novar/s, Janssen, Kite/Gilead and MSD and received research grants from Mnemo Therapeutics. R.D. reports honoraria from Novar/s and Takeda; and support for attending meetings and/or travel from Sanofi and Kite Pharma / Gilead. GM reports honoraria from Takeda, Bristol Myers Squibb, Gilead Kite, and Abbvie. All remaining authors have declared no conflicts of interest, (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)
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- 2024
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15. Real-world data for marginal zone lymphoma patients in the French REALYSA cohort: The REALMA study.
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Bommier C, Donzel M, Rossi C, Fornecker LM, Bijou F, Chauchet A, Lebras L, Ysabaert L, Haioun C, Bouabdallah K, Gastinne T, Morineau N, Amorim S, Jardin F, Abraham J, Lamy de la Chapelle T, Gressin R, Fouillet L, Fruchart C, Olivier G, Morschhauser F, Cherblanc F, Belot A, Le Guyader S, Monnereau A, Ghesquieres H, and Thieblemont C
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- Humans, Middle Aged, Male, Female, Aged, Adult, France epidemiology, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Prospective Studies, Rituximab administration & dosage, Rituximab therapeutic use, Survival Rate, Follow-Up Studies, Lymphoma, B-Cell, Marginal Zone therapy, Lymphoma, B-Cell, Marginal Zone pathology, Lymphoma, B-Cell, Marginal Zone diagnosis, Lymphoma, B-Cell, Marginal Zone epidemiology, Lymphoma, B-Cell, Marginal Zone mortality, Lymphoma, B-Cell, Marginal Zone drug therapy
- Abstract
Marginal Zone Lymphoma (MZL) comprises three subtypes: extranodal MZL (EMZL), splenic MZL (SMZL) and nodal MZL (NMZL). Since clinical trials have limited representativeness, there is a need for real-world data (RWD) evidence in MZL. Real-world data in Lymphoma and survival in Adults (REALYSA) is a prospective multicentric French cohort of newly diagnosed lymphoma patients. This study consists of the first abstraction of MZL patients prospectively included in REALYSA between 12/2018 and 01/2021 with at least 1 year of follow-up. It provides a landscape description of clinical characteristics, initial workup, quality of life and first-line therapy performed in routine practice. Among 207 included patients, 122 presented with EMZL, 51 with SMZL and 34 with NMZL. At baseline, median age was 67 years (range 28-96), and patients reported a favorable global health status (75/100 (IQR 58,83)) - which was higher in NMZL and lower in SMZL patients (p = 0.006).
18 FDG-PET/CT was frequently performed at initial workup (EMZL 72%, SMZL 73%, NMZL 85%). Active surveillance was the initial management for 58 (28%) patients. The most prescribed therapies were rituximab-chlorambucil in the EMZL population (30%), rituximab monotherapy in the SMZL population (37%) and R-CHOP (24%)/bendamustine-rituximab (15%) in the NMZL population. At end of first line, overall response rate was 93% among treated patients with 75% of complete response. This French nationwide study provided for the first time prospective RWD on clinical characteristics, initial management and treatment response of MZL patients., (© 2024 The Author(s). Hematological Oncology published by John Wiley & Sons Ltd.)- Published
- 2024
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16. Brexucabtagene autoleucel in relapsed or refractory mantle cell lymphoma, intention-to-treat use in the DESCAR-T registry.
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Herbaux C, Bret C, Bachy E, Bories P, Di Blasi R, Cuffel A, Gastinne T, Lamy T, Roussel M, Bouabdallah K, Beauvais D, Cartron G, Bay JO, Blaise D, Rubio MT, Mohty M, Le Bras F, Casasnovas O, Guy J, Guidez S, Llorente CC, Hermine O, La Rochelle LD, Carras S, Guffroy B, Caillat-Zucman S, Houot R, and Le Gouill S
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- 2024
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17. Novel prognostic scoring systems for severe CRS and ICANS after anti-CD19 CAR T cells in large B-cell lymphoma.
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Sesques P, Kirkwood AA, Kwon M, Rejeski K, Jain MD, Di Blasi R, Brisou G, Gros FX, le Bras F, Bories P, Choquet S, Rubio MT, Iacoboni G, O'Reilly M, Casasnovas RO, Bay JO, Mohty M, Joris M, Abraham J, Castilla Llorente C, Loschi M, Carras S, Chauchet A, La Rochelle LD, Hermine O, Guidez S, Cony-Makhoul P, Fogarty P, Le Gouill S, Morschhauser F, Gastinne T, Cartron G, Subklewe M, Locke FL, Sanderson R, Barba P, Houot R, and Bachy E
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- Humans, Male, Female, Middle Aged, Prognosis, Aged, Adult, Neurotoxicity Syndromes etiology, Biological Products therapeutic use, Biological Products adverse effects, France, Aged, 80 and over, Receptors, Antigen, T-Cell, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Antigens, CD19 immunology, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse immunology, Cytokine Release Syndrome etiology
- Abstract
Autologous anti-CD19 chimeric antigen receptor (CAR) T cells are now used in routine practice for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). Severe (grade ≥ 3) cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity (ICANS) are still the most concerning acute toxicities leading to frequent intensive care unit (ICU) admission, prolonging hospitalization, and adding significant cost to treatment. We report on the incidence of CRS and ICANS and the outcomes in a large cohort of 925 patients with LBCL treated with axicabtagene ciloleucel (axi-cel) or tisagenlecleucel (tisa-cel) in France based on patient data captured through the DESCAR-T registry. CRS of any grade occurred in 778 patients (84.1%), with 74 patients (8.0%) with grade 3 CRS or higher, while ICANS of any grade occurred in 375 patients (40.5%), with 112 patients (12.1%) with grade ≥ 3 ICANS. Based on the parameters selected by multivariable analyses, two independent prognostic scoring systems (PSS) were derived, one for grade ≥ 3 CRS and one for grade ≥ 3 ICANS. CRS-PSS included bulky disease, a platelet count < 150 G/L, a C-reactive protein (CRP) level > 30 mg/L and no bridging therapy or stable or progressive disease (SD/PD) after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 CRS. ICANS-PSS included female sex, low level of platelets (< 150 G/L), use of axi-cel and no bridging therapy or SD/PD after bridging. Patients with a CRS-PSS score > 2 had significantly higher risk to develop grade ≥ 3 ICANS. Both scores were externally validated in international cohorts of patients treated with tisa-cel or axi-cel., (© 2024. The Author(s).)
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- 2024
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18. Efficacy of CAR T-cell therapy is not impaired by previous bispecific antibody treatment in large B-cell lymphoma.
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Crochet G, Iacoboni G, Couturier A, Bachy E, Iraola-Truchuelo J, Gastinne T, Cartron G, Fradon T, Lesne B, Kwon M, Gounot R, Martínez-Cibrian N, Castilla-Llorente C, Abrisqueta P, Guerreiro M, Sarkozy C, Aspa-Cilleruelo JM, Camus V, Guidez S, Chauchet A, Deconinck E, Bouabdallah K, Bosch F, Barba P, Morschhauser F, and Houot R
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- Humans, Retrospective Studies, Male, Female, Middle Aged, Aged, Receptors, Chimeric Antigen immunology, Adult, Treatment Outcome, Antibodies, Bispecific therapeutic use, Immunotherapy, Adoptive methods, Lymphoma, Large B-Cell, Diffuse therapy, Lymphoma, Large B-Cell, Diffuse immunology
- Abstract
Abstract: In this retrospective study, chimeric antigen receptor T cells remained effective in patients with relapsed/refractory large B-cell lymphoma after prior exposure to bispecific antibodies (BsAbs) targeting different antigens. These results are relevant to clinical practice, particularly given the increasing use of BsAbs in earlier treatment lines., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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19. Author Correction: Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.
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Houot R, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, Gastinne T, Feugier P, Duléry R, Thieblemont C, Joris M, Jardin F, Choquet S, Casasnovas O, Brisou G, Cheminant M, Bay JO, Gutierrez FL, Menard C, Tarte K, Delfau MH, Portugues C, Itti E, Palard-Novello X, Blanc-Durand P, Al Tabaa Y, Bailly C, Laurent C, and Lemonnier F
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- 2024
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20. High efficacy of CD19 CAR T cells in patients with transformed Waldenström macroglobulinemia.
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Durot E, Roos-Weil D, Chauchet A, Decroocq J, Di Blasi R, Gastinne T, Bensaber H, Cheminant M, Jacquet C, Guidez S, Gros FX, Bachy E, Coste A, Cony-Makhoul P, Treon SP, Delmer A, Reshef R, Le Gouill S, Castillo JJ, and Houot R
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- Humans, Male, Aged, Female, Middle Aged, Receptors, Chimeric Antigen immunology, T-Lymphocytes immunology, T-Lymphocytes pathology, Treatment Outcome, Waldenstrom Macroglobulinemia therapy, Waldenstrom Macroglobulinemia immunology, Waldenstrom Macroglobulinemia pathology, Immunotherapy, Adoptive methods, Antigens, CD19 immunology
- Abstract
Abstract: Histologic transformation of Waldenström macroglobulinemia (HT-WM) carries a poor prognosis with standard treatments. Here, we report the first series of HT-WM treated with chimeric antigen receptor T cells showing a high efficacy and no unexpected toxicity., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)
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- 2024
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21. Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome (a DESCAR-T study).
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Vic S, Thibert JB, Bachy E, Cartron G, Gastinne T, Morschhauser F, Le Bras F, Bouabdallah K, Despas F, Bay JO, Rubio MT, Mohty M, Casasnovas O, Choquet S, Castilla-Llorente C, Guidez S, Loschi M, Guffroy B, Carras S, Drieu La Rochelle L, Guillet M, and Houot R
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- Humans, Middle Aged, Quality of Life, Neoplasm Recurrence, Local, Biomarkers, Antigens, CD19, Immunotherapy, Adoptive adverse effects, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
Abstract: Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell-related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion affects patients' quality of life, presents specific toxicities, and is known to affect immunity through the so-called transfusion-related immunomodulation that may affect CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients received transfusion in the 6-month period before and after CAR T-cell infusion, respectively. The number of patients receiving transfusion and the mean number of transfused products increased during the 6-month period before CAR T-cell infusion, peaked during the first month after infusion (early phase), and decreased over time. Predictive factors for transfusion at the early phase were age >60 years, ECOG PS ≥2, treatment with axicabtagene ciloleucel, pre-CAR T-cell transfusions, and CAR-HEMATOTOX score ≥2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre-CAR T-cell transfusions, CAR-HEMATOTOX score ≥2, ICANS ≥3 (for red blood cells [RBC] transfusion), and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and nonrelapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia and on the potential impact of transfusions on CAR T-cell efficacy and toxicity., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2024
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22. Long-Term Follow-Up of Rituximab Maintenance in Young Patients With Mantle-Cell Lymphoma Included in the LYMA Trial: A LYSA Study.
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Sarkozy C, Thieblemont C, Oberic L, Moreau A, Bouabdallah K, Damaj G, Gastinne T, Tessoulin B, Ribrag V, Casasnovas O, Haioun C, Houot R, Jardin F, Van Den Neste E, Cheminant M, Morschhauser F, Callanan M, Safar V, Gressin R, Hermine O, and Le Gouill S
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- Adult, Humans, Rituximab therapeutic use, Follow-Up Studies, Transplantation, Autologous, Antineoplastic Combined Chemotherapy Protocols adverse effects, Lymphoma, Mantle-Cell drug therapy, Hematopoietic Stem Cell Transplantation methods
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned coprimary or secondary analyses are not yet available. Clinical trial updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. The LYMA trial demonstrated the benefit of rituximab maintenance (RM) in first-line young patients with mantle-cell lymphoma. In this prolonged follow-up of 7.5 years (95% CI, 7.4 to 7.7) from inclusion, the median progression-free survival (PFS) and overall survival (OS) for the full population were not reached (NR) with a 7-year PFS of 55.5% (95% CI, 49.5 to 61) and OS of 69.5% (95% CI, 63.8 to 74.5). The EFS remained statistically superior in favor of RM (median NR v 5.8 years, P < .0001; HR, 0.39 [95% CI, 0.52 to 0.6] and 7-year estimate, 76.2% versus 46% for RM and observation, respectively). Similarly, RM prolonged PFS (estimated PFS at 7 years, 78.5% v 47.4% and HR, 0.36 [95% CI, 0.23 to 0.56] for RM and observation, respectively, P < .0001). The 7-year OS estimate was 83.2% versus 72.2%, respectively ( P = .088, HR, 0.63 [95% CI, 0.37 to 1.08]). Cause of death was not significantly distinct between the two groups, with lymphoma being the leading cause with a very low rate of infection-related death. Overall, the PFS benefit of RM after autologous stem cell transplantation remains after 7-year follow-up, and RM was not associated with an increase in infection-related mortality, making this strategy a safe standard of care with long-term follow-up.
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- 2024
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23. Phase I study of zoledronic acid combined with escalated doses of interleukine-2 for early in vivo generation of Vγ9Vδ2 T-cells after haploidentical stem cell transplant with posttransplant cyclophosphamide.
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Jullien M, Guillaume T, Le Bourgeois A, Peterlin P, Garnier A, Eveillard M, Le Bris Y, Bouzy S, Tessoulin B, Gastinne T, Dubruille V, Touzeau C, Mahé B, Blin N, Lok A, Vantyghem S, Sortais C, Antier C, Moreau P, Scotet E, Béné MC, and Chevallier P
- Subjects
- Humans, Interleukin-2, Zoledronic Acid, T-Lymphocytes pathology, Cyclophosphamide therapeutic use, Stem Cell Transplantation, Hematopoietic Stem Cell Transplantation methods, Graft vs Host Disease etiology, Graft vs Host Disease prevention & control, Graft vs Host Disease drug therapy
- Abstract
The presence of donor Vγ9Vδ2 T-cells after haploidentical hematopoietic stem cell transplant (h-HSCT) has been associated with improved disease-free survival. These cells kill tumor cells in a non-MHC restricted manner, do not induce graft-versus-host disease (GVHD), and can be generated by stimulation with zoledronic acid (ZA) in combination with interleukin-2 (IL-2). This monocentric phase I, open-label, dose-escalating study (ClinicalTrials.gov: NCT03862833) aimed at evaluating the safety and possibility to generate Vγ9Vδ2 T-cells early after h-HSCT. It applied a standard 3 + 3 protocol to determine the maximum tolerated dose (MTD) of increasing low-doses of IL-2 (5 days [d] per week, 4 weeks) in combination with a single dose of ZA, starting both the first Monday after d + 15 posttransplant. Vγ9Vδ2 T-cell monitoring was performed by multiparameter flow cytometry on blood samples and compared with a control cohort of h-HSCT recipients. Twenty-six patients were included between April 2019 and September 2022, 16 of whom being ultimately treated and seven being controls who received h-HSCT only. At the three dose levels tested, 1, 0, and 1 dose-limiting toxicities were observed. MTD was not reached. A significantly higher number of Vγ9Vδ2 T-cells was observed during IL-2 treatment compared with controls. In conclusion, early in vivo generation of Vγ9Vδ2 T-cells is feasible after h-HSCT by using a combination of ZA and repeated IL-2 infusions. This study paves the way to a future phase 2 study, with the hope to document lesser posttransplant relapse with this particular adaptive immunotherapy., (© 2024 Wiley Periodicals LLC.)
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- 2024
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24. Features and outcomes of patients admitted to the ICU for chimeric antigen receptor T cell-related toxicity: a French multicentre cohort.
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Le Cacheux C, Couturier A, Sortais C, Houot R, Péré M, Gastinne T, Seguin A, Reignier J, Lascarrou JB, Tadié JM, Quelven Q, and Canet E
- Abstract
Background: Chimeric antigen receptor T-cell (CAR-T) therapy is increasingly used in patients with refractory haematological malignancies but can induce severe adverse events. We aimed to describe the clinical features and outcomes of patients admitted to the intensive care unit (ICU) after CAR-T therapy., Methods: This retrospective observational cohort study included consecutive adults admitted to either of two French ICUs in 2018-2022 within 3 months after CAR-T therapy., Results: Among 238 patients given CAR-T therapy, 84 (35.3%) required ICU admission and were included in the study, a median of 5 [0-7] days after CAR-T infusion. Median SOFA and SAPSII scores were 3 [2-6] and 39 [30-48], respectively. Criteria for cytokine release syndrome were met in 80/84 (95.2%) patients, including 18/80 (22.5%) with grade 3-4 toxicity. Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 46/84 (54.8%) patients, including 29/46 (63%) with grade 3-4 toxicity. Haemophagocytic lymphohistiocytosis was diagnosed in 15/84 (17.9%) patients. Tocilizumab was used in 73/84 (86.9%) patients, with a median of 2 [1-4] doses. Steroids were given to 55/84 (65.5%) patients, including 21/55 (38.2%) given high-dose pulse therapy. Overall, 23/84 (27.4%) patients had bacterial infections, 3/84 (3.6%) had fungal infections (1 invasive pulmonary aspergillosis and 2 Mucorales), and 2 (2.4%) had cytomegalovirus infection. Vasopressors were required in 23/84 (27.4%), invasive mechanical ventilation in 12/84 (14.3%), and dialysis in 4/84 (4.8%) patients. Four patients died in the ICU (including 2 after ICU readmission, i.e., overall mortality was 4.8% of patients). One year after CAR-T therapy, 41/84 (48.9%) patients were alive and in complete remission, 14/84 (16.7%) were alive and in relapse, and 29/84 (34.5%) had died. These outcomes were similar to those of patients never admitted to the ICU., Conclusion: ICU admission is common after CAR-T therapy and is usually performed to manage specific toxicities. Our experience is encouraging, with low ICU mortality despite a high rate of grade 3-4 toxicities, and half of patients being alive and in complete remission at one year., (© 2024. The Author(s).)
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- 2024
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25. Quad-class exposed/refractory myeloma is associated with short survival.
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Piron B, Costes-Tertrais D, Gastinne T, Fourmont AM, Dubruille V, Blin N, Moreau P, Touzeau C, and Tessoulin B
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- Humans, Retrospective Studies, Prognosis, B-Cell Maturation Antigen, Immunotherapy, Adoptive, Multiple Myeloma drug therapy, Immunoconjugates, Antibodies, Bispecific therapeutic use
- Abstract
Very scarce data exist about outcomes of relapsed multiple myeloma patients who have failed proteasome inhibitor, immunomodulatory drug, anti-CD38 monoclonal antibody and therapies targeting B-cell maturation antigen (BCMA) (Quad-class exposed [QCE]). In this retrospective single-centre study, we determined progression-free survival (PFS) and overall survival (OS) from anti-BCMA failure in 45 QCE patients. Seven (16%) patients received antibody-drug conjugate, 20 (44%) bispecific antibodies and 18 (40%) CAR-T cell. Thirty patients (67%) received ≥1 subsequent line of treatment. PFS was 4.4 months (95% CI = 2.4-12.5) and OS 6.3 months (95% CI = 3.9-14.4). Having an adverse prognosis, QCE myeloma patients remain an unmet medical need., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)
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- 2024
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26. Immune-related adverse events with bispecific T-cell engager therapy targeting B-cell maturation antigen.
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Piron B, Bastien M, Antier C, Dalla-Torre R, Jamet B, Gastinne T, Dubruille V, Moreau P, Martin J, Bénichou A, Touzeau C, and Tessoulin B
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- Humans, T-Lymphocytes, B-Cell Maturation Antigen, Antibodies, Bispecific adverse effects
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- 2024
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27. Comparison of efficacy and toxicity according to etoposide and cytarabine dosing in BEAM conditioning followed by autologous stem cell transplantation in Hodgkin lymphoma.
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Vély A, Couturier MA, Delepine P, Le Calloch R, Ertault M, Gastinne T, Plichon C, Lebreton A, Lester MA, Larhantec G, Cormier N, Fouquet S, Houot R, Tanguy-Schmidt A, Hunault-Berger M, and Orvain C
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- Humans, Etoposide adverse effects, Retrospective Studies, Transplantation, Autologous, Cytarabine adverse effects, Carmustine adverse effects, Melphalan adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Hodgkin Disease diagnosis, Hodgkin Disease therapy, Hematopoietic Stem Cell Transplantation adverse effects, Mucositis chemically induced
- Abstract
The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) is a commonly used intensification regimen for patients with Hodgkin lymphoma. As etoposide and cytarabine dosing are not defined, we conducted a retrospective, multicenter study, to compare efficacy and toxicity in 130 patients with Hodgkin lymphoma receiving etoposide and cytarabine at either 200 mg/m
2 /d ( n = 50), 400 mg/m2 /d ( n = 35), or etoposide 200 mg/m2 /d and cytarabine 400 mg/m2 /d ( n = 45). Progression-free survival and overall survival were not associated with the intensity of conditioning. Increased conditioning intensity was associated with longer duration of thrombocytopenia, a higher number of transfused RBC and platelet units and a higher frequency of mucositis, but serious adverse events or infectious complications were not increased. The intensity of BEAM regimen was not associated with survival but with the rate of cytopenia and mucositis advocating for the use of lower dosing in frail patients.- Published
- 2023
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28. Nonrelapse mortality after CAR T-cell therapy for large B-cell lymphoma: a LYSA study from the DESCAR-T registry.
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Lemoine J, Bachy E, Cartron G, Beauvais D, Gastinne T, Di Blasi R, Rubio MT, Guidez S, Mohty M, Casasnovas RO, Joris M, Castilla-Llorente C, Haioun C, Hermine O, Loschi M, Carras S, Bories P, Fradon T, Herbaux C, Sesques P, Le Gouill S, Morschhauser F, Thieblemont C, and Houot R
- Subjects
- Humans, Risk Factors, Antigens, CD19, Immunotherapy, Adoptive adverse effects, Immunotherapy, Adoptive methods, Lymphoma, Large B-Cell, Diffuse pathology
- Abstract
CD19 chimeric antigen receptor (CAR) T cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory large B-cell lymphomas. However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the nonrelapse mortality (NRM) after CAR T-cell therapy. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM and identified risk factors of NRM. We report on 957 patients who received standard-of-care axicabtagene ciloleucel (n = 598) or tisagenlecleucel (n = 359) between July 2018 and April 2022, in 27 French centers. With a median follow-up of 12.4 months, overall NRM occurred in 48 patients (5.0% of all patients): early (before day 28 after infusion) in 9 patients (0.9% of all patients and 19% of overall NRM), and late (on/after day 28 after infusion) in 39 patients (4.1% of all patients and 81% of overall NRM). Causes of overall NRM were distributed as follows: 56% infections (29% with non-COVID-19 and 27% with COVID-19), 10% cytokine release syndromes, 6% stroke, 6% cerebral hemorrhage, 6% second malignancies, 4% immune effector cell associated neurotoxicities, and 10% deaths from other causes. We report risk factors of early NRM and overall NRM. In multivariate analysis, both diabetes and elevated ferritin level at lymphodepletion were associated with an increased risk of overall NRM. Our results may help physicians in patient selection and management in order to reduce the NRM after CAR T-cell therapy., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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29. Improving Diagnosis of Pulmonary Mucormycosis: Leads From a Contemporary National Study of 114 Cases.
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Coste A, Conrad A, Porcher R, Poirée S, Peterlin P, Defrance C, Letscher-Bru V, Morio F, Gastinne T, Bougnoux ME, Suarez F, Nevez G, Dupont D, Ader F, Halfon-Domenech C, Ducastelle-Leprêtre S, Botterel F, Millon L, Guillerm G, Ansart S, Boutoille D, Ledoux MP, Herbrecht JE, Robin C, Melica G, Danion F, Blanchard E, Paccoud O, Garcia-Hermoso D, Lortholary O, Herbrecht R, and Lanternier F
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- Humans, Retrospective Studies, Mucormycosis diagnosis, Mucormycosis therapy, Lung Diseases, Fungal diagnosis, Neutropenia
- Abstract
Background: Pulmonary mucormycosis (PM) is a life-threatening invasive mold infection. Diagnosis of mucormycosis is challenging and often delayed, resulting in higher mortality., Research Question: Are the disease presentation of PM and contribution of diagnosis tools influenced by the patient's underlying condition?, Study Design and Methods: All PM cases from six French teaching hospitals between 2008 and 2019 were retrospectively reviewed. Cases were defined according to updated European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria with the addition of diabetes and trauma as host factors and positive serum or tissue PCR as mycologic evidence. Thoracic CT scans were reviewed centrally., Results: A total of 114 cases of PM were recorded, including 40% with disseminated forms. Main underlying conditions were hematologic malignancy (49%), allogeneic hematopoietic stem cell transplantation (21%), and solid organ transplantation (17%). When disseminated, main dissemination sites were the liver (48%), spleen (48%), brain (44%), and kidneys (37%). Radiologic presentation included consolidation (58%), pleural effusion (52%), reversed halo sign (26%), halo sign (24%), vascular abnormalities (26%), and cavity (23%). Serum quantitative polymerase chain reaction (qPCR) was positive in 42 (79%) of 53 patients and BAL in 46 (50%) of 96 patients. Results of transthoracic lung biopsy were diagnostic in 8 (73%) of 11 patients with noncontributive BAL. Overall 90-day mortality was 59%. Patients with neutropenia more frequently displayed an angioinvasive presentation, including reversed halo sign and disseminated disease (P < .05). Serum qPCR was more contributive in patients with neutropenia (91% vs 62%; P = .02), and BAL was more contributive in patients without neutropenia (69% vs 41%; P = .02). Serum qPCR was more frequently positive in patients with a > 3 cm main lesion (91% vs 62%; P = .02). Overall, positive qPCR was associated with an early diagnosis (P = .03) and treatment onset (P = .01)., Interpretation: Neutropenia and radiologic findings influence disease presentation and contribution of diagnostic tools during PM. Serum qPCR is more contributive in patients with neutropenia and BAL examination in patients without neutropenia. Results of lung biopsies are highly contributive in cases of noncontributive BAL., Competing Interests: Financial/Nonfinancial Disclosures The authors have reported to CHEST the following: A. Coste has received a travel grant from the association Marie-Bertille. O. L. has received speaker's fees from MSD, Gilead, Astellas, Pfizer, and F2G, and is consultant for Gilead. F. L. has received personal fees from Gilead, F2G and Pfizer. R. H. has received a grant from Gilead and personal honoraria from Pfizer, Gilead, and Mundipharma. L. M. has received travel grants from Gilead and Pfizer. F. D. has received personal fees from Gilead, outside the submitted work. None declared (A. Conrad, R. P., S. P., P. P., C. D., V. L.-B., F. M., T. G., M.-E. B., F. S., G. N., D. D., F. A., C. H.-D., S. D.-L., F. B., G. G., S. A., D. B., M.-P. L., J.-E. H., C. R., G. M., E. B., O. P., D. G.-H.)., (Copyright © 2023 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)
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- 2023
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30. Publisher Correction: Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.
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Houot R, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, Gastinne T, Feugier P, Duléry R, Thieblemont C, Joris M, Jardin F, Choquet S, Casasnovas O, Brisou G, Cheminant M, Bay JO, Gutierrez FL, Menard C, Tarte K, Delfau MH, Portugues C, Itti E, Palard-Novello X, Blanc-Durand P, Al Tabaa Y, Bailly C, Laurent C, and Lemonnier F
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- 2023
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31. Axicabtagene ciloleucel as second-line therapy in large B cell lymphoma ineligible for autologous stem cell transplantation: a phase 2 trial.
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Houot R, Bachy E, Cartron G, Gros FX, Morschhauser F, Oberic L, Gastinne T, Feugier P, Duléry R, Thieblemont C, Joris M, Jardin F, Choquet S, Casasnovas O, Brisou G, Cheminant M, Bay JO, Gutierrez FL, Menard C, Tarte K, Delfau MH, Portugues C, Itti E, Palard-Novello X, Blanc-Durand P, Al Tabaa Y, Bailly C, Laurent C, and Lemonnier F
- Subjects
- Humans, Transplantation, Autologous, Cytokine Release Syndrome, Immunotherapy, Adoptive adverse effects, Antigens, CD19, Hematopoietic Stem Cell Transplantation, Lymphoma, Large B-Cell, Diffuse therapy, Biological Products therapeutic use
- Abstract
Axicabtagene ciloleucel (axi-cel) demonstrated superior efficacy compared to standard of care as second-line therapy in patients with high-risk relapsed/refractory (R/R) large B cell lymphoma (LBCL) considered eligible for autologous stem cell transplantation (ASCT); however, in clinical practice, roughly half of patients with R/R LBCL are deemed unsuitable candidates for ASCT. The efficacy of axi-cel remains to be ascertained in transplant-ineligible patients. ALYCANTE, an open-label, phase 2 study, evaluated axi-cel as a second-line therapy in 62 patients with R/R LBCL who were considered ineligible for ASCT. The primary end point was investigator-assessed complete metabolic response at 3 months from the axi-cel infusion. Key secondary end points included progression-free survival, overall survival and safety. The study met its primary end point with a complete metabolic response of 71.0% (95% confidence interval, 58.1-81.8%) at 3 months. With a median follow-up of 12.0 months (range, 2.1-17.9), median progression-free survival was 11.8 months (95% confidence interval, 8.4-not reached) and overall survival was not reached. There was no unexpected toxicity. Grade 3-4 cytokine release syndrome and neurologic events occurred in 8.1% and 14.5% of patients, respectively. These results support axi-cel as second-line therapy in patients with R/R LBCL ineligible for ASCT. ClinicalTrials.gov Identifier: NCT04531046 ., (© 2023. The Author(s).)
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- 2023
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32. Hodgkin lymphoma and female fertility: a multicenter study in women treated with doxorubicin, bleomycin, vinblastine, and dacarbazine.
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Machet A, Poudou C, Tomowiak C, Gastinne T, Gardembas M, Systchenko T, Moya N, Debiais C, Levy A, Gruchet C, Sabirou F, Noel S, Bouyer S, Leleu X, Delwail V, and Guidez S
- Subjects
- Pregnancy, Child, Infant, Newborn, Humans, Female, Adolescent, Young Adult, Adult, Vinblastine adverse effects, Bleomycin adverse effects, Dacarbazine adverse effects, Doxorubicin adverse effects, Antineoplastic Combined Chemotherapy Protocols adverse effects, Fertility, Hodgkin Disease complications, Hodgkin Disease drug therapy
- Abstract
Preservation of fertility has become a growing concern in young females with Hodgkin lymphoma (HL). However, the rate of pregnancy after the current most frequently prescribed ABVD (doxorubicin [Adriamycin], bleomycin, vinblastine, and darcarbazine) chemotherapy for HL has rarely been studied. In this study, we aim to determine the impact of ABVD on the fertility of women treated for HL. We conducted a noninterventional, multicenter study of female patients of childbearing age who were treated for HL. Two healthy apparied women nonexposed to chemotherapy (our controls) were assigned for each patient. Fertility was assessed by the number of pregnancies and births after HL treatment. Sixty-seven patients were included. The median age at diagnosis was 24.4 years (range, 16-43). HL was a localized disease for 68.7%. Of all the patients, 53.7% started at least 1 pregnancy after treatment vs 54.5% of the controls (P = .92). Of all the patients who desired children, 81% had at least 1 pregnancy. Patients treated with ABVD did not have a longer median time to pregnancy (4.8 years in the group of patients and 6.8 years for controls). Across patients, there were 58 pregnancies and 48 births (ratio, 1:2) and 136 pregnancies and 104 births (ratio, 1:3) for the control cohort. No increase in obstetric or neonatal complications has been reported in HL in our study. The number of pregnancies, births, and the time to start a pregnancy in young women treated with ABVD for HL is not different from that of controls. Therefore, females with HL treated with ABVD should be reassured regarding fertility., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
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- 2023
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33. Randomized Phase III Trial Evaluating Subcutaneous Rituximab for the First-Line Treatment of Low-Tumor Burden Follicular Lymphoma: Results of a LYSA Study.
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Cartron G, Bachy E, Tilly H, Daguindau N, Pica GM, Bijou F, Mounier C, Clavert A, Damaj GL, Slama B, Casasnovas O, Houot R, Bouabdallah K, Sibon D, Fitoussi O, Morineau N, Herbaux C, Gastinne T, Fornecker LM, Haioun C, Launay V, Araujo C, Benbrahim O, Sanhes L, Gressin R, Gonzalez H, Morschhauser F, Ternant D, Xerri L, Tarte K, and Pranger D
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- Humans, Rituximab, Tumor Burden, Antineoplastic Combined Chemotherapy Protocols adverse effects, Progression-Free Survival, Lymphoma, Follicular pathology
- Abstract
Purpose: Rituximab improves progression-free survival (PFS) and time to next treatment (TTNT) when compared with the watch and wait strategy for patients with low-tumor burden follicular lymphoma (FL). Prolonged rituximab maintenance did not prolong TTNT, whereas it raises concerns about resources use and patient adhesion. Our aim was then to investigate the use of short rituximab maintenance using the subcutaneous (SC) route in patients with low-tumor burden FL., Methods: Patients with histologically confirmed CD20
+ low-tumor burden FL were randomly assigned to receive either rituximab, 375 mg/m2 once daily on D1, D8, D15, and D22, intravenous route (IV, control arm), or rituximab, 375 mg/m2 , on day 1 (D1), IV followed by rituximab 1,400 mg total dose, SC once daily on D8, D15, and D22, with maintenance at months 3 (M3), M5, M7, and M9 (experimental arm). The primary end point was PFS. Secondary end points included safety, overall response rates, TTNT, and overall survival (OS)., Results: Two hundred two patients with low-tumor burden FL were randomly assigned to the experimental (n = 100) or control arm (n = 102). The primary end point was met: the 4-year PFS was 58.1% (95% CI, 47.5 to 67.4) and 41.2% (95% CI, 30.6 to 51.6) in experimental and control arms, respectively (hazard ratio, 0.585 [0.393 to 0.871]; P = .0076). Complete response (CR) rates were 59.0% (95% CI, 48.7 to 68.7) in the experimental arm and 36.3% (95% CI, 27.0 to 46.4) in the control arm ( P = .001). TTNT and OS were not significantly different. CR was associated with longer PFS and TTNT. High rituximab exposure during the first three months was independently associated with higher CR, PFS, and TTNT., Conclusion: SC rituximab improves PFS for patients with low-tumor burden FL when used in induction followed by short maintenance. High rituximab exposure during the first 3 months after treatment initiation is, however, the only parameter influencing patient outcomes.- Published
- 2023
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34. Failure to bispecific-antibody therapy is associated with a short survival in highly pre-treated patients with aggressive B-Cell Lymphomas.
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Kevork K, Gouin M, Letailleur V, Chevallier P, Touzeau C, Gastinne T, Piron B, and Tessoulin B
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- Humans, Lymphoma, B-Cell drug therapy, Antibodies, Bispecific therapeutic use
- Abstract
Competing Interests: Declaration of Competing Interest We have no Conflict of Interest to declare.
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- 2023
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35. Outcomes of patients with aggressive B-cell lymphoma after failure of anti-CD19 CAR T-cell therapy: a DESCAR-T analysis.
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Di Blasi R, Le Gouill S, Bachy E, Cartron G, Beauvais D, Le Bras F, Gros FX, Choquet S, Bories P, Feugier P, Casasnovas O, Bay JO, Mohty M, Joris M, Gastinne T, Sesques P, Tudesq JJ, Vercellino L, Morschhauser F, Gat E, Broussais F, Houot R, and Thieblemont C
- Subjects
- Humans, Neoplasm Recurrence, Local pathology, Antigens, CD19, T-Lymphocytes, Immunotherapy, Adoptive adverse effects, Lymphoma, B-Cell
- Abstract
Anti-CD19 chimeric antigen receptor (CAR) T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experience failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age-adjusted International Prognostic Index of 2 to 3, 18.9% had Eastern Cooperative Oncology Group performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease, and 38.9% had high lactate dehydrogenase (LDH). Failure after CAR T-cell treatment occurred after a median of 2.7 months (range: 0.2-21.5). Fifty-four patients (22.7%) presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 patients (64%) received salvage treatment: 38.3% received lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immunochemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 vs after D30 was 1.7 vs 3.0 months, respectively (P = .0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure
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- 2022
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36. Prognostic value of TARC and quantitative PET parameters in relapsed or refractory Hodgkin lymphoma patients treated with brentuximab vedotin and DHAP.
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Driessen J, Kersten MJ, Visser L, van den Berg A, Tonino SH, Zijlstra JM, Lugtenburg PJ, Morschhauser F, Hutchings M, Amorim S, Gastinne T, Nijland M, Zwezerijnen GJC, Boellaard R, de Vet HCW, Arens AIJ, Valkema R, Liu RDK, Drees EEE, de Jong D, Plattel WJ, and Diepstra A
- Subjects
- Humans, Brentuximab Vedotin, Prognosis, Prospective Studies, Stem Cell Transplantation, Neoplasm Recurrence, Local diagnostic imaging, Neoplasm Recurrence, Local drug therapy, Positron-Emission Tomography, Vitamin D therapeutic use, Hodgkin Disease diagnostic imaging, Hodgkin Disease drug therapy, Immunoconjugates therapeutic use
- Abstract
Risk-stratified treatment strategies have the potential to increase survival and lower toxicity in relapsed/refractory classical Hodgkin lymphoma (R/R cHL) patients. This study investigated the prognostic value of serum (s)TARC, vitamin D and lactate dehydrogenase (LDH), TARC immunohistochemistry and quantitative PET parameters in 65 R/R cHL patients who were treated with brentuximab vedotin (BV) and DHAP followed by autologous stem-cell transplantation (ASCT) within the Transplant BRaVE study (NCT02280993). At a median follow-up of 40 months, the 3-year progression free survival (PFS) was 77% (95% CI: 67-88%) and the overall survival was 95% (90-100%). Significant adverse prognostic markers for progression were weak/negative TARC staining of Hodgkin Reed-Sternberg cells in the baseline biopsy, and a high standard uptake value (SUV)mean or SUVpeak on the baseline PET scan. After one cycle of BV-DHAP, sTARC levels were strongly associated with the risk of progression using a cutoff of 500 pg/ml. On the pre-ASCT PET scan, SUVpeak was highly prognostic for progression post-ASCT. Vitamin D, LDH and metabolic tumor volume had low prognostic value. In conclusion, we established the prognostic impact of sTARC, TARC staining, and quantitative PET parameters for R/R cHL, allowing the use of these parameters in prospective risk-stratified clinical trials. Trial registration: NCT02280993., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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37. Final results of brentuximab vedotin combined with ifosfamide-carboplatin-etoposide in first refractory/relapsed Hodgkin lymphoma: a lymphoma study association phase I/II study.
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Stamatoullas A, Ghesquières H, Feugier P, André M, Le Bras F, Gac AC, Borel C, Gastinne T, Quittet P, Morschhauser F, Ribrag V, Guidez S, Nicolas-Virelizier E, Berriolo-Riedinger A, Vander Borght T, Edeline V, and Brice P
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- Humans, Brentuximab Vedotin therapeutic use, Carboplatin therapeutic use, Etoposide therapeutic use, Ifosfamide therapeutic use, Immunoconjugates therapeutic use, Treatment Outcome, Antineoplastic Combined Chemotherapy Protocols adverse effects, Hodgkin Disease drug therapy, Lymphoma drug therapy, Neoplasm Recurrence, Local drug therapy
- Abstract
This phase I/II study assessed the combination of brentuximab vedotin (BV) with ifosfamide-carboplatin-etoposide (ICE) as a second-line therapy in refractory/relapsed (R/R) classical Hodgkin lymphoma (cHL) patients. Phase I study was designed to determine the maximum tolerated dose (MTD) of BV (10 patients) and phase II evaluated the rate of complete metabolic response (CMR) after 2 cycles of BV-ICE (42 patients). There were no dose-limiting toxicities (DLT) during phase I recommending BV 1.8 mg/kg for phase II. Twenty-six patients (61.9%) achieved CMR after 2 cycles of BV-ICE and 37 patients (88%) were transplanted. With a median follow-up of 38 months, the 3-year progression free survival (PFS) and overall survival (OS) rate were 64.3% and 100%, respectively. Hematological toxicities (81%) and infections (21%) were the most frequent adverse event encountered BV-ICE regimen is feasible with manageable toxicities and could be an alternative to other salvage treatments. Trial Registration : ClinicalTrials.gov identifier: NCT02686346.
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- 2022
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38. Radiotherapy or Autologous Stem-Cell Transplantation for Primary CNS Lymphoma in Patients Age 60 Years and Younger: Long-Term Results of the Randomized Phase II PRECIS Study.
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Houillier C, Dureau S, Taillandier L, Houot R, Chinot O, Moluçon-Chabrot C, Schmitt A, Gressin R, Choquet S, Damaj G, Peyrade F, Abraham J, Delwail V, Gyan E, Sanhes L, Cornillon J, Garidi R, Delmer A, Al Jijakli A, Morel P, Waultier A, Paillassa J, Chauchet A, Gastinne T, Laadhari M, Plissonnier AS, Feuvret L, Cassoux N, Touitou V, Ricard D, Hoang-Xuan K, and Soussain C
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- Humans, Middle Aged, Adolescent, Young Adult, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Neoplasm Recurrence, Local drug therapy, Transplantation, Autologous, Combined Modality Therapy, Central Nervous System Neoplasms pathology, Hematopoietic Stem Cell Transplantation adverse effects, Hematopoietic Stem Cell Transplantation methods, Lymphoma radiotherapy, Lymphoma drug therapy
- Abstract
Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported. We previously reported the results of a randomized phase II study in patients with newly diagnosed primary CNS lymphoma (age 18-60 years). Patients were treated with high-dose methotrexate-based induction chemotherapy followed by whole-brain radiotherapy (WBRT) or high-dose chemotherapy (thiotepa-busulfan-cyclophosphamide) with autologous stem-cell transplantation (ASCT). The median follow-up was 33 months. In this report, we provide long-term data (median follow-up, 8 years) regarding the outcomes and toxicities. Fifty-three and 44 patients received induction chemotherapy followed by WBRT or ASCT, respectively. Their 8-year event-free survival from random assignment was 67% and 39% in the ASCT and WBRT arms, respectively ( P = .03), with a significantly lower risk of relapse after ASCT (hazard ratio, 0.13; P < .001). One third of patients who relapsed after WBRT were alive after salvage treatment. Five and four patients died of ASCT and WBRT-related toxicities, respectively. The 8-year overall survival was 69% and 65% in the ASCT and WBRT arms, respectively (not significant). Balance (52% v 10%, P ≤ 0.001) and neurocognition (64% v 13%, P < .001) significantly deteriorated after WBRT compared with ASCT during the follow-up. This study shows that 40 Gy WBRT should be avoided in first-line treatment because of its neurotoxicity and suboptimal efficacy in reducing relapses while ASCT appears to be highly efficient in preventing relapses.
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- 2022
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39. Clinical presentation, outcome, and prognostic markers in patients with intravascular large B-cell lymphoma, a lymphoma study association (LYSA) retrospective study.
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Bonnet A, Bossard C, Gabellier L, Rohmer J, Laghmari O, Parrens M, Sarkozy C, Dulery R, Roland V, Llamas-Gutierrez F, Oberic L, Fornecker LM, Bounaix L, Villemagne B, Szablewski V, Choquet S, Bouabdallah K, Traverse-Glehen A, Mohty M, Sanhes L, Houot R, Gastinne T, Leux C, and Le Gouill S
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- Adult, Aged, Aged, 80 and over, Antineoplastic Combined Chemotherapy Protocols adverse effects, Cyclophosphamide therapeutic use, Doxorubicin therapeutic use, Humans, Methotrexate therapeutic use, Middle Aged, Prednisone therapeutic use, Prognosis, Proto-Oncogene Proteins c-bcl-2, Retrospective Studies, Rituximab therapeutic use, Vincristine therapeutic use, Young Adult, Lymphoma, Large B-Cell, Diffuse diagnosis, Lymphoma, Large B-Cell, Diffuse drug therapy, Lymphoma, Large B-Cell, Diffuse pathology, Macrophage Activation Syndrome drug therapy, Macrophage Activation Syndrome etiology
- Abstract
Background: Intravascular large B-cell lymphoma (lVLBCL) is a very rare type of large B-cell lymphoma., Methods: We conducted a retrospective study on IVLBCL patients treated from 2000 to 2016 in LYSA cooperative group centers., Results: Sixty-five patients were identified in 23 centers. Median age at diagnosis was 69 years (range 23-92). Thirty-four patients (64%) had an IPI score >3 and 40 patients (67%) had a performance status ≥2. The most frequent extra-nodal locations were bone marrow (n = 34; 52%), central nervous system (n = 25; 39%), and skin (n = 21; 33%). Nodal involvement and endocrine system were observed in 34% (n = 22) and 18% (n = 12) of all cases, respectively. Twenty-six patients (41%) had macrophage activation syndrome. Tumor cells were frequently CD5 positive (52%) with a non-germinal center origin (86%). BCL2 was expressed in 87% of all samples analyzed (n = 20) and 43% of patients had a MYC/BCL2 double expression. Fifty-six patients were treated with a regimen of chemotherapy containing rituximab, among whom 73% reached complete remission. The median progression-free survival (PFS) and median overall survival (OS) were 29.4 months and 63.8 months, respectively. History of autoimmune disorder (Hazard ratio [HR] 3.3 [1.4-7.8]; p < 0.01), nodal involvement (HR 2.6 [1.4-5.1]; p < 0.01), lack of anthracycline (HR 0.1 [0-0.4] for use; p < 0.001), or no intensification at first-line regimen (p = 0.02) were associated with worse PFS. High-dose methotrexate use was not associated with better PFS or OS., Conclusions: Our study highlights the aggressive clinical picture of IVLBCL, in particular the frequency of macrophage activation syndrome, and the need for new therapies despite a response to R-CHOP-like regimen similar to non-intravascular diffuse large B-cell lymphomas., (© 2022 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)
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- 2022
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40. Prognostic value of FDG-PET/CT response for patient selection before chimeric antigen receptor-T-cells therapy in non-Hodgkin lymphoma.
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Bailly C, Carlier T, Tessoulin B, Gastinne T, Kraeber-Bodere F, Le Gouill S, and Bodet-Milin C
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- Fluorodeoxyglucose F18, Humans, Patient Selection, Positron Emission Tomography Computed Tomography, Positron-Emission Tomography, Prognosis, Retrospective Studies, T-Lymphocytes pathology, Lymphoma, Non-Hodgkin diagnostic imaging, Lymphoma, Non-Hodgkin pathology, Lymphoma, Non-Hodgkin therapy, Receptors, Chimeric Antigen
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- 2022
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41. A real-world comparison of tisagenlecleucel and axicabtagene ciloleucel CAR T cells in relapsed or refractory diffuse large B cell lymphoma.
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Bachy E, Le Gouill S, Di Blasi R, Sesques P, Manson G, Cartron G, Beauvais D, Roulin L, Gros FX, Rubio MT, Bories P, Bay JO, Llorente CC, Choquet S, Casasnovas RO, Mohty M, Guidez S, Joris M, Loschi M, Carras S, Abraham J, Chauchet A, Drieu La Rochelle L, Deau-Fischer B, Hermine O, Gastinne T, Tudesq JJ, Gat E, Broussais F, Thieblemont C, Houot R, and Morschhauser F
- Subjects
- Antigens, CD19, Clinical Studies as Topic, Cytokine Release Syndrome, Humans, Retrospective Studies, T-Lymphocytes, Biological Products adverse effects, Immunotherapy, Adoptive adverse effects, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse therapy, Receptors, Chimeric Antigen therapeutic use
- Abstract
Axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) have both demonstrated impressive clinical activity in relapsed/refractory (R/R) diffuse large B cell lymphoma (DLBCL). In this study, we analyzed the outcome of 809 patients with R/R DLBCL after two or more previous lines of treatment who had a commercial chimeric antigen receptor (CAR) T cells order for axi-cel or tisa-cel and were registered in the retrospective French DESCAR-T registry study ( NCT04328298 ). After 1:1 propensity score matching (n = 418), the best overall response rate/complete response rate (ORR/CRR) was 80%/60% versus 66%/42% for patients treated with axi-cel compared to tisa-cel, respectively (P < 0.001 for both ORR and CRR comparisons). After a median follow-up of 11.7 months, the 1-year progression-free survival was 46.6% for axi-cel and 33.2% for tisa-cel (hazard ratio (HR) = 0.61; 95% confidence interval (CI), 0.46-0.79; P = 0.0003). Overall survival (OS) was also significantly improved after axi-cel infusion compared to after tisa-cel infusion (1-year OS 63.5% versus 48.8%; HR = 0.63; 95% CI, 0.45-0.88; P = 0.0072). Similar findings were observed using the inverse probability of treatment weighting statistical approach. Grade 1-2 cytokine release syndrome was significantly more frequent with axi-cel than with tisa-cel, but no significant difference was observed for grade ≥3. Regarding immune effector cell-associated neurotoxicity syndrome (ICANS), both grade 1-2 and grade ≥3 ICANS were significantly more frequent with axi-cel than with tisa-cel. In conclusion, our matched comparison study supports a higher efficacy and also a higher toxicity of axi-cel compared to tisa-cel in the third or more treatment line for R/R DLBCL., (© 2022. The Author(s).)
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- 2022
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42. Humoral immune depression following autologous stem cell transplantation is a marker of prolonged response duration in patients with mantle cell lymphoma.
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Bouard L, Tessoulin B, Thieblemont C, Bouabdallah K, Gastinne T, Oberic L, Carras S, Delette C, Casasnovas O, Dartigeas C, Cacheux V, Masse S, Hermine O, and Le Gouill S
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Depression, Humans, Rituximab therapeutic use, Stem Cell Transplantation, Transplantation, Autologous adverse effects, Agammaglobulinemia etiology, Hematopoietic Stem Cell Transplantation adverse effects, Lymphoma, Mantle-Cell drug therapy, Lymphopenia etiology, Neutropenia
- Abstract
Rituximab maintenance (RM) after autologous stem cell transplantation (ASCT) is standard-of-care for young patients with mantle cell lymphoma (MCL). RM may enhance post-transplantation immune depression and risk of infections. We compared infection incidence and immune consequences of RM versus observation in transplanted MCL patients. All randomized patients included in the LyMa trial were eligible. The following parameters were collected prospectively: occurrence of fever, infection, hospitalization, neutropenia, hypogammaglobulinemia, CD4 lymphopenia and γ globulin (Ig) substitution. The post-ASCT period was divided into four periods in order to assess the possible effects of RM or ASCT on immune status. Each arm included 120 patients. Concerning infection incidence and all biological parameters, there was no difference between the two arms during the first year post ASCT. After this period, RM patients were more exposed to fever (P=0.03), infections (P=0.001), hypogammaglobulinemia (P=0.0001) and Ig substitution (P<0.0001). Incidences of hospitalization, neutropenia and CD4 lymphopenia were not different between the two arms. The number of rituximab injections was correlated with infections and hypogammaglobulinemia, P<0.0001 and P=0.001; but was not correlated with neutropenia and CD4 lymphopenia. Ig substitution did not modify infection incidence. Patients who presented hypogammaglobulinemia <6 g/L or <4 g/L had longer 3-years progression-free survival (PFS), this applies to RM patients (P=0.012 and P=0.03) and to the global cohort (P=0.008 and P=0.003). Hypogammaglobulinemia did not influence overall survival. Occurrence of infectious event, neutropenia and CD4 lymphopenia did neither influence PFS nor overall survival. Post-ASCT RM in MCL patients causes sustained hypogammaglobulinemia, which is independently correlated with improved PFS.
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- 2022
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43. Safety and risk of febrile recurrence after early antibiotic discontinuation in high-risk neutropenic patients with haematological malignancies: a multicentre observational study.
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Paret R, Le Bourgeois A, Guillerm G, Tessoulin B, Rezig S, Gastinne T, Couturier MA, Boutoille D, Lecomte R, Ader F, Le Gouill S, Ansart S, Talarmin JP, and Gaborit B
- Subjects
- Anti-Bacterial Agents adverse effects, Humans, Prospective Studies, Bacteremia complications, Bacteremia drug therapy, Fever of Unknown Origin chemically induced, Fever of Unknown Origin complications, Fever of Unknown Origin drug therapy, Hematologic Neoplasms complications, Hematologic Neoplasms drug therapy, Leukemia, Myeloid, Acute complications, Neoplasms complications, Neutropenia chemically induced, Neutropenia complications, Neutropenia drug therapy
- Abstract
Background: Early antibiotic discontinuation according to the Fourth European Conference on Infections in Leukaemia (ECIL-4) recommendations is not systematically applied in high-risk neutropenic patients with haematological malignancies., Methods: A retrospective multicentre observational study was conducted over 2 years to evaluate the safety of early antibiotic discontinuation for fever of unknown origin (FUO) during neutropenia after induction chemotherapy or HSCT, in comparison with a historical cohort. We used Cox proportional hazards models, censored on neutropenia resolution, to analyse factors associated with febrile recurrence., Results: Among 147 included patients in the ECIL-4 cohort, mainly diagnosed with acute leukaemia (n = 104, 71%), antibiotics were discontinued during 170 post-chemotherapy neutropenic episodes. In comparison with the historical cohort of 178 episodes of neutropenia without antibiotic discontinuation, no significant differences were observed regarding febrile recurrences [71.2% (121/170) versus 71.3% (127/178), P = 0.97], admission in ICUs [6.5% (11/170) versus 11.2% (20/178), P = 0.17], septic shock [0.6% (1/170) versus 3.9% (7/178), P = 0.07] and 30 day mortality [1.4% (2/147) versus 2.7% (4/150), P = 0.084]. In the ECIL-4 cohort, the rate of bacteraemia in case of febrile recurrence was higher [27.1% (46/170) versus 11.8% (21/178), P < 0.01] and antibiotic consumption was significantly lower (15.5 versus 19.9 days, P < 0.001). After early antibiotic discontinuation according to ECIL-4 recommendations, enterocolitis was associated with febrile recurrence [HR = 2.31 (95% CI = 1.4-3.8), P < 0.001] and stage III-IV oral mucositis with bacteraemia [HR = 2.26 (95% CI = 1.22-4.2), P = 0.01]., Conclusions: After an FUO episode in high-risk neutropenia, compliance with ECIL-4 recommendations for early antibiotic discontinuation appears to be safe and mucosal damage was associated with febrile recurrence and bacteraemia. Prospective interventional studies are warranted to assess this strategy in high-risk neutropenic patients., (© The Author(s) 2022. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
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- 2022
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44. Outcomes of refractory or relapsed Hodgkin lymphoma patients with post-autologous stem cell transplantation brentuximab vedotin maintenance: a French multicenter observational cohort study.
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Marouf A, Cottereau AS, Kanoun S, Deschamps P, Meignan M, Franchi P, Sibon D, Antoine C, Gastinne T, Borel C, Hammoud M, Sicard G, Gille R, Cavalieri D, Stamatoullas A, Filliatre-Clement L, Lazarovici J, Chauchet A, Fornecker LM, Amorin S, Rocquet M, Raus N, Burroni B, Rubio MT, Bouscary D, Quittet P, Casasnovas RO, Brice P, Ghesquieres H, Tamburini J, and Deau B
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- Brentuximab Vedotin, Humans, Salvage Therapy, Stem Cell Transplantation, Transplantation, Autologous, Hematopoietic Stem Cell Transplantation, Hodgkin Disease drug therapy, Immunoconjugates therapeutic use
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- 2022
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45. B Cell Aplasia Is the Most Powerful Predictive Marker for Poor Humoral Response after BNT162b2 mRNA SARS-CoV-2 Vaccination in Recipients of Allogeneic Hematopoietic Stem Cell Transplantation.
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Jullien M, Le Bourgeois A, Coste-Burel M, Peterlin P, Garnier A, Rimbert M, Imbert BM, Le Gouill S, Moreau P, Mahe B, Dubruille V, Blin N, Lok A, Touzeau C, Gastinne T, Tessoulin B, Vantyghem S, Béné MC, Guillaume T, and Chevallier P
- Subjects
- BNT162 Vaccine, Biomarkers, CD8-Positive T-Lymphocytes, COVID-19 Vaccines, Humans, RNA, Messenger, SARS-CoV-2, Vaccination, COVID-19 prevention & control, Hematopoietic Stem Cell Transplantation methods
- Abstract
Little is known about the immune response to SARS-CoV-2 vaccination in recipients of allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, several studies have reported that adequate protection could be provided to this population. The purpose of this study was to evaluate which factors can predict the efficacy of SARS-CoV-2 vaccination in these specifically immunosuppressed patients. Specific anti-Spike (S) antibody responses were assessed in a cohort of 117 allo-HSCT recipients after 2 injections of BNT162b2 mRNA SARS-CoV-2 vaccine (V1 and V2). Factors considered liable to influence the antibody response and analyzed in this series were the interval between allo-HSCT and V1, donor source, recipient and donor age, current immunosuppressive/chemotherapy (I/C) treatment, and levels of CD4
+ and CD8+ T cells, B cells, and natural killer cells at the time of V1. Overall, the S-antibody response rate, evaluated at a median of 35 days after V2, was 82.9% for the entire cohort, with 71 patients (61%) reaching the highest titer. In univariate analysis, a lower pre-V1 median total lymphocyte count, lower CD4+ T cell and B cell counts, ongoing I/C treatment, and a haploidentical donor were characteristic of nonhumoral responders. However, multiparameter analysis showed that B cell aplasia was the sole factor predicting the absence of a specific immune response (odds ratio, 0.01; 95% confidence interval, 0.00 to 0.10; P < 10-3 ). Indeed, the rate of humoral response was 9.1% in patients with B cell aplasia versus 95.9% in patients with a B cell count >0 (P < 10-9 ). These results advocate for the administration of anti-SARS-CoV-2 vaccination in allo-HSCT recipients as early as peripheral B cell levels can be detected, and also suggest the need for close monitoring of B-cell reconstitution after Allo-HSCT., (Copyright © 2022 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)- Published
- 2022
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46. Bendamustine-EAM versus R-BEAM after high-dose cytarabine-based induction in newly diagnosed patients with mantle cell lymphoma, a LYSA retrospective study.
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Costes-Tertrais D, Hueso T, Gastinne T, Thieblemont C, Oberic L, Bouabdallah K, Garciaz S, Tchernonog E, Dartigeas C, Ribrag V, Fogarty P, Casasnovas RO, Houot R, Delette C, Malak S, Fornecker LM, Gressin R, Damaj G, and Le Gouill S
- Subjects
- Adult, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Bendamustine Hydrochloride therapeutic use, Carmustine pharmacology, Carmustine therapeutic use, Cytarabine therapeutic use, Etoposide, Humans, Melphalan therapeutic use, Retrospective Studies, Transplantation, Autologous methods, Hematopoietic Stem Cell Transplantation methods, Lymphoma, Mantle-Cell drug therapy
- Abstract
Cytarabine-based immuno-chemotherapy followed by autologous stem cell transplantation (ASCT) consolidation is standard of care for fit patients with Mantle Cell Lymphoma (MCL). BEAM (Carmustine, Etoposide, Aracytine, Melphalan) is among the most frequently used conditioning regimen. Studies comparing BEAM with Bendamustine-EAM (BeEAM) have suggested that patients treated with BeEAM have a better progression-free survival (PFS). We performed a cross-study analysis to better evaluate BeEAM. Thirty-five patients from a retrospective study who received R-DHAP/BeEAM were compared to 245 patients from the LyMa trial (NCT00921414) who all received R-DHAP followed by R-BEAM. PFS and Overall Survival (OS) were estimated using Kaplan-Meier methods. At 2 years there was no difference between R-BEAM and BeEAM in either PFS (84.9% versus 87.9%; p = 0.95) or OS (91.8% versus 94.2%; p = 0.30). Analyses were repeated on a propensity score to reduce biases. Each patient from the BeEAM cohort (n = 30) was matched to three patients from the R-BEAM cohort (n = 90) for age, sex, MIPI score, pre-transplant status disease and rituximab maintenance (RM). PFS and OS at 2 years remained similar between R-BEAM and BeEAM with more renal toxicity in BeEAM group. MCL patients who received R-DHAP induction before ASCT have similar outcome after R-BEAM or BeEAM conditioning regimen., (© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)
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- 2022
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47. Positron Emission Tomography-Driven Strategy in Advanced Hodgkin Lymphoma: Prolonged Follow-Up of the AHL2011 Phase III Lymphoma Study Association Study.
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Casasnovas RO, Bouabdallah R, Brice P, Lazarovici J, Ghesquieres H, Stamatoullas A, Dupuis J, Gac AC, Gastinne T, Joly B, Bouabdallah K, Nicolas-Virelizier E, Feugier P, Morschhauser F, Sibon D, Bonnet C, Berriolo-Riedinger A, Edeline V, Parrens M, Damotte D, Coso D, André M, Meignan M, and Rossi C
- Subjects
- Adolescent, Adult, Antineoplastic Combined Chemotherapy Protocols adverse effects, Bleomycin, Cyclophosphamide, Dacarbazine, Doxorubicin, Etoposide, Follow-Up Studies, Humans, Middle Aged, Neoplasm Staging, Positron-Emission Tomography methods, Prednisone, Procarbazine, Vinblastine, Vincristine, Young Adult, Hodgkin Disease diagnostic imaging, Hodgkin Disease drug therapy, Neoplasms, Second Primary pathology
- Abstract
Purpose: The AHL2011 study (ClinicalTrials.gov identifier: NCT01358747) demonstrated that a positron emission tomography (PET)-driven de-escalation strategy after two cycles of bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine, and prednisone (BEACOPP) provides similar progression-free survival (PFS) and overall survival (OS) and reduces early toxicity compared with a nonmonitored standard treatment. Here, we report, with a prolonged follow-up, the final study results., Methods: Patients with advanced Hodgkin lymphoma (stage III, IV, or IIB with mediastinum/thorax ratio > 0.33 or extranodal involvement) age 16-60 years were prospectively randomly assigned between 6 × BEACOPP and a PET-driven arm after 2 × BEACOPP delivering 4 × ABVD (doxorubicin, bleomycin, vinblastine, and dacarbazine) in PET2- and 4 × BEACOPP in PET2+ patients. PET performed after four cycles of chemotherapy had to be negative to complete the planned treatment., Results: In total, 823 patients were enrolled including 413 in the standard arm and 410 in the PET-driven arm. With a 67.2-month median follow-up, 5-year PFS (87.5% v 86.7%; hazard ratio [HR] = 1.07; 95% CI, 0.74 to 1.57; P = .67) and OS (97.7% in both arms; HR = 1.012; 95% CI, 0.50 to 2.10; P = .53) were similar in both randomization arms. In the whole cohort, full interim PET assessment predicted patients' 5-year PFS (92.3% in PET2-/PET4-, 75.4% [HR = 3.26; 95% CI, 18.3 to 5.77] in PET2+/PET4- and 46.5% [HR = 12.4; 95% CI, 7.31 to 19.51] in PET4+ patients, respectively; P < .0001) independent of international prognosis score. Five-year OS was also affected by interim PET results, and PET2+/PET4- patients (93.5%; HR = 3.3; 95% CI, 1.07 to 10.1; P = .036) and PET4+ patients (91.9%; HR = 3.756; 95% CI, 1.07 to 13.18; P = .038) had a significant lower OS than PET2-/PET4- patients (98.2%). Twenty-two patients (2.7%) developed a second primary malignancy, 13 (3.2%) and 9 (2.2%) in the standard and experimental arms, respectively., Conclusion: The extended follow-up confirms the continued efficacy and favorable safety of AHL2011 PET-driven strategy, which is noninferior to standard six cycles of BEACOPP. PET4 provides additional prognostic information to PET2 and allows identifying patients with particularly poor prognosis., Competing Interests: René-Olivier CasasnovasHonoraria: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, AmgenConsulting or Advisory Role: Roche/Genentech, Takeda, Gilead Sciences, Bristol Myers Squibb, Merck, AbbVie, Celgene, Janssen, IncyteResearch Funding: Roche/Genentech (Inst), Gilead Sciences (Inst), Takeda (Inst)Travel, Accommodations, Expenses: Roche/Genentech, Takeda, Gilead Sciences, Janssen Pauline BriceResearch Funding: Takeda, BMSTravel, Accommodations, Expenses: Roche, Amgen, AbbVie/Genentech Julien LazaroviciTravel, Accommodations, Expenses: Mundipharma Hervé GhesquieresHonoraria: Gilead Sciences, Janssen, Celgene, RocheConsulting or Advisory Role: Gilead Sciences, Celgene, Roche, MundipharmaTravel, Accommodations, Expenses: Roche, Gilead Sciences, Celgene, Takeda Aspasia StamatoullasTravel, Accommodations, Expenses: Pfizer Jehan DupuisConsulting or Advisory Role: AstraZenecaTravel, Accommodations, Expenses: Gilead Sciences Thomas GastinneHonoraria: Pfizer, Takeda, Gilead SciencesConsulting or Advisory Role: Takeda, Gilead SciencesTravel, Accommodations, Expenses: Roche, Pfizer Krimo BouabdallahHonoraria: Roche, Takeda Science Foundation, AbbVie, Kite/GileadConsulting or Advisory Role: Roche, Takeda, Kite/GileadTravel, Accommodations, Expenses: Roche, Takeda Pierre FeugierHonoraria: Roche/Genentech, Janssen, Gilead Sciences, Amgen, AbbVieConsulting or Advisory Role: Roche/Genentech, Janssen, AbbVie, Gilead Sciences, Amgen, AstraZenecaSpeakers' Bureau: Roche/Genentech, AbbVie, Amgen, Janssen, Gilead SciencesResearch Funding: Roche/Genentech, Gilead Sciences, Janssen, AbbVie, AmgenTravel, Accommodations, Expenses: Amgen, Gilead Sciences, Janssen, Roche/Genentech, AbbVie Franck MorschhauserConsulting or Advisory Role: Roche/Genentech, Gilead Sciences, Celgene, Bristol Myers Squibb, AbbVie, Epizyme, ServierSpeakers' Bureau: RocheExpert Testimony: Roche/Genentech David SibonConsulting or Advisory Role: Takeda, Iqone healthcare, Janssen, Roche, AbbVieTravel, Accommodations, Expenses: Takeda, Janssen Christophe BonnetConsulting or Advisory Role: Roche Diane DamotteResearch Funding: AstraZeneca/MedImmune Marc AndréConsulting or Advisory Role: Takeda, BMSiResearch Funding: Takeda (Inst), Roche (Inst)Travel, Accommodations, Expenses: Roche, Celgene, Gilead Sciences Michel MeignanHonoraria: RocheTravel, Accommodations, Expenses: Roche Cédric RossiConsulting or Advisory Role: Janssen, AbbVie, Roche, TakedaResearch Funding: TakedaTravel, Accommodations, Expenses: AbbVieNo other potential conflicts of interest were reported.
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- 2022
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48. Interest of a third dose of BNT162b2 anti-SARS-CoV-2 messenger RNA vaccine after allotransplant.
- Author
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Le Bourgeois A, Coste-Burel M, Guillaume T, Peterlin P, Garnier A, Imbert BM, Drumel T, Mahé B, Dubruille V, Blin N, Lok A, Touzeau C, Gastinne T, Tessoulin B, Jullien M, Vantyghem S, Moreau P, Le Gouill S, Béné MC, and Chevallier P
- Subjects
- Adult, Aged, Allografts, Antibodies, Viral immunology, Antibody Formation, BNT162 Vaccine administration & dosage, COVID-19 immunology, Female, Humans, Male, Middle Aged, Organ Transplantation, Retrospective Studies, SARS-CoV-2 immunology, Stem Cell Transplantation, Transplantation, Homologous, Young Adult, BNT162 Vaccine therapeutic use, COVID-19 prevention & control
- Published
- 2022
- Full Text
- View/download PDF
49. Extensive myelitis with eosinophilic meningitis after Chimeric antigen receptor T cells therapy.
- Author
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Le Calvez B, Eveillard M, Decamps P, Aguilar J, Seguin A, Canet E, Grain A, Touzeau C, Tessoulin B, and Gastinne T
- Abstract
Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent adverse event after Chimeric antigen receptor T cells (CAR-T cells). A patient treated with anti-CD19 CAR-T cells for a refractory mantle cell lymphoma presented at Day 8 post-infusion with extensive myelitis. Unusual eosinophilia was disclosed in the patient's cerebrospinal fluid. After treatment with methylprednisolone and siltuximab, a decrease in clinical symptoms and magnetic resonance imaging lesions were obtained. This unprecedented presentation of eosinophilic meningitis after CAR-T cells therapy highlights the need for a better understanding of the physiopathology of ICANS, especially to identify potentially targetable pathways., Competing Interests: The authors declare that they have no conflict of interest., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)
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- 2022
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50. Safety and antibody response after one and/or two doses of BNT162b2 Anti-SARS-CoV-2 mRNA vaccine in patients treated by CAR T cells therapy.
- Author
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Gastinne T, Le Bourgeois A, Coste-Burel M, Guillaume T, Peterlin P, Garnier A, Imbert BM, Drumel T, Mahe B, Dubruille V, Blin N, Lok A, Touzeau C, Tessoulin B, Jullien M, Vanthygem S, Béné MC, Moreau P, Le Gouill S, and Chevallier P
- Subjects
- Adult, Aged, Antigens, Viral immunology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, BNT162 Vaccine adverse effects, Biological Products therapeutic use, Combined Modality Therapy, Female, Fever etiology, Hematopoietic Stem Cell Transplantation, Humans, Immunization, Secondary, Immunocompromised Host, Immunogenicity, Vaccine, Lymphoma, Non-Hodgkin immunology, Lymphoma, Non-Hodgkin therapy, Male, Middle Aged, Pain etiology, Precursor Cell Lymphoblastic Leukemia-Lymphoma immunology, Precursor Cell Lymphoblastic Leukemia-Lymphoma therapy, Receptors, Antigen, T-Cell therapeutic use, Receptors, Chimeric Antigen therapeutic use, Spike Glycoprotein, Coronavirus immunology, Vaccination, Young Adult, Antibodies, Viral biosynthesis, BNT162 Vaccine immunology, COVID-19 prevention & control, Immunoglobulin G biosynthesis, Immunotherapy, Adoptive, SARS-CoV-2 immunology
- Published
- 2022
- Full Text
- View/download PDF
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