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575 Outcomes of Primary Mediastinal B-Cell Lymphoma Patients Treated with a PET-Guided Strategy in the Randomized Phase 3 Gained Study Conducted By Lysa

Program: Oral and Poster Abstracts
Type: Oral
Session: 626. Aggressive Lymphomas: Clinical and Epidemiological: Challenging Subtypes of Aggressive Lymphomas
Sunday, December 8, 2024: 1:00 PM

Vincent Camus, MD, PhD1,2*, Thierry Jo Molina, MD, PhD3*, Fabienne Desmots-Loyer, PhD4*, Amine Moslemi, MD5*, Philippe Ruminy, PhD2*, Steven Le Gouill, MD, PhD6, Herve Ghesquieres, MD, PhD7*, Lucie Oberic, MD8*, Franck Morschhauser9, Hervé Tilly2, Vincent Ribrag, MD10, Roch Houot, MD, PhD11*, Catherine Thieblemont, MD12, Herve Maisonneuve, MD13*, Fabien Claves, MD14*, Krimo Bouabdallah, MD15*, Corinne Haioun, MD, PhD16, Gandhi Damaj, MD, PhD17*, Luc-Matthieu Fornecker, MD, PhD18*, Robin Noel, MD19*, Pierre Feugier, MD, PhD20*, David Sibon, MD, PhD21*, Guillaume Cartron, MD, PhD22,23*, Christophe Bonnet, MD, PhD24*, Marc André, MD, PhD25*, Françoise Kraeber-Bodéré, MD, PhD26,27*, Caroline Milin, MD, PhD26,27*, Jean-Philippe Jais, MD, PhD28*, Josette Briere, MD29*, Olivier Casasnovas, MD30,31*, Salim Kanoun, MD32,33*, Emmanuel Itti, MD, PhD34*, Paul Blanc-Durand35*, Mad-Hélénie Elsensohn36*, Loic Chartier37*, Fabrice Jardin, MD, PhD2* and Thierry Fest, MD, PhD38,39*

1Centre Henri Becquerel, Department of Hematology, Rouen, France
2INSERM U1245, Cancer and Brain Genomics, Centre Henri Becquerel, University of Rouen, Rouen, France
3Department of Pathology, Assistance Publique-Hôpitaux de Paris, Necker and Robert Debré Hospital, Université Paris Cité, Paris, France
4Laboratoire d'Hématologie, Université de Rennes 1, INSERM, Établissement Français du Sang de Bretagne, Team B_DEVIL, UMR_S1236, Rennes, France; Centre Hospitalier Universitaire, RENNES, France
5Department of Pathology, Amiens University Hospital, Amiens, FRA
6Institut Curie, Saint-Cloud, France
7Department of Hematology, Centre Hospitalier Lyon-Sud, Hospices Civils de Lyon, Université Claude Bernard Lyon 1, Lyon, France
8IUCT - Oncopole, Hematology Department, Toulouse, France
9Centre Hospitalier Universitaire de Lille - Hopital Claude Huriez, Lille, France
10Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Gustave Roussy Institute of Cancer, Villejuif, France
11Hematology department, CHU Rennes - Hopital Pontchaillou, Rennes, France
12Hospital Saint-Louis, Paris, France
13Centre Hospitalier Departemental de Vendée, La Roche-sur-Yon, FRA
14Department of Hematology, University Hospital Grenoble - HOPITAL ALBERT MICHALLON, Grenoble, France
15Bordeaux university hospital, Haut-Leveque, Department of hematology, Bordeaux, France
16Lymphoid Malignancies Department, Henri Mondor University Hospital, AP-HP, Créteil, France
17CHU Caen, Caen, Normandy, FRA
18Institut De Cancérologie Strasbourg Europe, Hematology Department, Strasbourg, France
19Institut Paoli-Calmettes, Marseille, FRA
20CHU Brabois - Service d'Hématologie - Université Henri Poincaré, Nancy, France
21Lymphoid Hematology Department, Henri Mondor University Hospital, AP-HP, Paris, France
22Centre Hospitalier Universitaire de Montpellier, Montpellier, France
23Montpellier University Hospital Center, UMR CNRS 5535, Montpellier, France
24Hématologie clinique, CHU de Liège, Université de Liège, Liège, Belgium
25CHU UCL Namur, Yvoir, Belgium
26CRCINA, INSERM, CNRS, Université d'Angers, Université de Nantes, Nantes, France
27Department of Nuclear Medicine, University Hospital of Nantes, Nantes, France
28Hôpital Necker-Enfants Malades, PARIS, France
29University Hospital Henri-Mondor, APHP, INSERM U955, Créteil, FRA
30François Mitterand Hospital, Dijon, FRA
31INSERM 1231, Dijon, France
32Pixilib SAS, ; Centre de Recherche Clinique de Toulouse, Team 9 INSERM Unité Mixte de Recherche 1037, Toulouse, France
33Nucear Medicine Department, IUCT Oncopole, Toulouse, France
34Nuclear medicine department, Henri Mondor University Hospital, AP-HP, Créteil, FRA
35CHU Henri Mondor, Creteil, FRA
36Lymphoma Academic Research Organization (LYSARC), Lyon, France
37Department of Biostatistics, Lymphoma Academic Research Organization (LYSARC), Lyon, France
38Inserm, Université de Rennes 1, Rennes, France
39Laboratoire d'Hématologie, Centre Hospitalier Universitaire de Rennes, INSERM, Établissement Français du Sang de Bretagne, Team B_DEVIL, UMR_S1236, Rennes, France

Introduction: The GAINED study (NCT01659099) was a randomized phase 3 trial comparing obinutuzumab (G) to rituximab (R) plus ACVBP or CHOP14 induction, followed by PET-guided consolidation. No significant survival differences were found between the arms (Le Gouill et al. 2021). This post-hoc analysis aimed to detail the outcomes of primary mediastinal B-cell lymphoma (PMBL) patients included in the trial, verified through expert pathological review and the use of a molecular gene-expression profiling-based (GEP) classifier.

Methods: Conducted by LYSA across 99 centers in Belgium and France from 2012 to 2015, the GAINED study had the following key inclusion criteria : patients aged 18-60 years, CD20+ diffuse large B-cell lymphoma (DLBCL) according to the 2008 WHO classification, aaIPI ≥1, and eligibility for autologous stem cell transplant (ASCT). Patients with a ΔSUVmax >66% after cycle 2 and >70% after cycle 4 (PET2−/4−) received standard consolidation chemotherapy, while those with PET2+/4− received intensive treatment with ASCT. PET4+ patients (ΔSUVmax ≤70%) were given salvage therapy. We here focused on clinical characteristics, treatment responses, and outcomes, incorporating metabolic tumor volume (MTV, fixed SUV4 method) and biological data including cell-free DNA (cfDNA) and soluble PDL1 (sPDL1) levels, mutational landscape (custom targeted NGS panel), and GEP (LymphoSign test). Primary endpoints included were progression-free survival (PFS) and overall survival (OS). False discovery rate correction was applied for multiple testing.

Results: Of the initial 670 patients, 138 (20.6%) confirmed PMBL cases were analyzed. Baseline characteristics included a median age of 33.5 years, 63.8% female, 55.1% stage III-IV, 90.6% elevated LDH, 87% ECOG 0-1, 62.3% extranodal involvement, 52.2% aaIPI 2-3, 50.7% MTV ≥360 cm³, and 53.6% with bulky (>10cm) mediastinal masses. Induction regimens were R/G-CHOP14 (56.5%) and R/G-ACVBP (42.8%). Post-induction treatments, based on interim PET (iPET) results, included: consolidation chemotherapy (55.1%), ASCT (24.6%), and salvage therapy (12.3%). After a median follow-up of 39.5 months, 2-year PFS and OS rates were 86.2%, and 93.2%. PET2−/4− had superior PFS (p<0.001) but similar OS (p=0.123) compared to PET2+/4− and PET4+ patients; the 2-year PFS and OS were: 93.5% vs 82.4% vs 58.8% and 96% vs 90.9% vs 85.6% respectively. ACVBP plus ASCT (n=38) and CHOP14 plus ASCT (n=38) had similar 2-year PFS and OS: 94.6% vs 92.1% and 97.1% vs 94.7%. ACVBP plus sequential consolidation chemotherapy and CHOP14 8 cycles had also comparable 2-year PFS and OS: 81.8% vs 82.6% and 90.9% vs 90.9%.

Among patients with GEP data (n=107), 38 (35.5%) were PDL1high/PDL2high. Key somatic mutations data (n=87) included SOCS1 (70.1%), B2M (56.3%), STAT6 (49.4%), TNFAIP3 (47.1%), GNA13 (39.1%), CIITA (37.9%), CD58 (36.8%), and TP53 (29.9%).

Univariate analysis highlighted that bulky mass (HR 4.37 [95%CI: 1.48-12.92]), stage III-IV (HR 4.06 [1.38-12.01]), and PET4+ (HR 3.18 [1.07-9.48]) were associated with shorter PFS, whereas PET2- and ΔSUVmax PET4 (continuous variable) where associated with longer PFS (HR=0.48 [0.16-1.44] and 0.26 [0.15-0.43], respectively). Additionally, stage III-IV (HR 9.9 [1.28-76.57]) was linked to shorter OS, whereas ΔSUVmax PET4 was associated with longer OS (HR=0.36 [0.21-0.62]). None of the other factors assessed (aaIPI, induction chemotherapy regimen, R or G, cfDNA and sPDL1 level, PDL1high/PDL2high status, B2M, CD58, TP53 alterations, MTV) were significantly associated with outcomes.

Finally, in multivariate models, bulky mass adjusted on aaIPI remained significantly associated with inferior PFS (HR 3.84 [1.11-13.27], p=0.034). When MTV and ΔSUVmax PET2 and PET4 were also included, only ΔSUVmax PET4 was associated with longer PFS (HR=0.21 [0.08-0.55], p=0.001) and OS (HR=0.46 [0.23-0.93], p=0.032).

Conclusion: This analysis highlights the strong representation, distinct characteristics and excellent outcomes of PMBL patients in the GAINED trial, emphasizing the importance of expert histopathological and molecular characterization for accurate diagnosis. The iPET response, especially ΔSUVmax PET4, emerged as the primary predictor of outcomes in this selected clinical trial population. Tailoring consolidation treatments based on iPET results may have mitigated the impact of baseline adverse characteristics.

Disclosures: Ghesquieres: Roche, BMS, Takeda: Consultancy; Gilead, Roche, BMS, Abbvie, Takeda: Honoraria. Oberic: Janssen: Honoraria; Beigene: Honoraria; Kite, a Gilead Company: Honoraria; Roche: Honoraria. Morschhauser: Roche: Consultancy, Honoraria; Janssen: Honoraria; AbbVie: Consultancy, Honoraria; Takeda: Honoraria; Chugai: Honoraria; BMS: Consultancy; Novartis: Consultancy; Kite/Gilead: Consultancy. Tilly: F. Hoffmann-La Roche Ltd: Membership on an entity's Board of Directors or advisory committees, Research Funding; ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Incyte: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees. Ribrag: Belgene: Speakers Bureau; Employment: Ended employment in the past 24 months; AstraZeneca: Honoraria; AstraZeneca, Lilly: Membership on an entity's Board of Directors or advisory committees; Astex, GSK: Research Funding; Pegascy: Current Employment; Abbvie, Ipsen: Speakers Bureau. Thieblemont: AstraZeneca: Honoraria; ADC Therapeutics: Honoraria; Incyte Corporation: Consultancy, Honoraria, Speakers Bureau; Sanofi: Honoraria; Novartis: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Cellectis: Honoraria; Janssen: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; Bayer: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Roche: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; BeiGene: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria, Other: Travel and accommodations, Research Funding, Speakers Bureau; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; Takeda: Consultancy, Honoraria, Other: Travel and Accommodation, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Other: Travel and accommodation, Research Funding, Speakers Bureau; Amgen: Consultancy, Honoraria, Other: Travel and accommodation, Speakers Bureau; University of Paris: Current Employment, Ended employment in the past 24 months; Regeneron: Consultancy, Honoraria. Cartron: Roche, BMS, AbbVie, Ownards therapeutics, MAbQi, MedXcell, BeiGene: Consultancy; Janssen: Honoraria; Beigene: Consultancy, Honoraria; Gilead: Honoraria; MAbQi: Consultancy; Novartis: Honoraria; Ownards therapeutics: Consultancy; Takeda: Honoraria; MedXcell: Consultancy; Roche: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria; Roche, BMS, Gilead, Novartis, Takeda, Beigen, Janssen, AbbVie: Honoraria. André: Bristol-Myers-Squibb: Consultancy, Other: travel grants; takeda: Consultancy, Other: travel grants, Research Funding; Gilead: Consultancy, Other: travel grants; Roche: Other: travel grants, Research Funding; Incyte: Consultancy; abbaye: Other: travel grants; astrazeneca: Other: travel grants; celgene: Other: travel grants. Casasnovas: Kite-Gilead: Honoraria. Jardin: Janssen: Honoraria; Abbvie: Honoraria; Roche: Honoraria; Novartis: Honoraria; Kite, a Gilead Company: Honoraria.

*signifies non-member of ASH