Camus Vincent, Molina Thierry, Desmots Fabienne, Blanc-Durand Paul, Kanoun Salim, Moslemi Amine, Ruminy Philippe, Le Gouill Steven, Ghesquières Hervé, Oberic Lucie, Morschhauser Franck, Tilly Hervé, Ribrag Vincent, Houot Roch, Thieblemont Catherine, Maisonneuve Hervé, Claves Fabien, Bouabdallah Krimo, Haioun Corinne, Damaj Gandhi Laurent, Fornecker Luc-Matthieu, Noel Robin, Feugier Pierre, Sibon David, Cartron Guillaume, Bonnet Christophe, Bernard Wivine, Kraeber-Bodéré Françoise, Bodet-Milin Caroline, Jais Jean-Philippe, Brière Josette, Rossi Cedric, Elsensohn Mad-Hélénie, Chartier Loïc, Itti Emmanuel, Jardin Fabrice, Fest Thierry
Department of Hematology, Centre Henri Becquerel, Rouen, France.
INSERM U1245, Centre Henri Becquerel, University of Rouen, Rouen, France.
Blood Adv. 2025 May 13;9(9):2232-2246. doi: 10.1182/bloodadvances.2024015577.
The GAINED study was a randomized phase 3 trial comparing obinutuzumab (G) with rituximab (R) plus ACVBP (doxorubicin, cyclophosphamide, and prednisone, combined with either vindesine or bleomycin) or CHOP14 (cyclophosphamide, doxorubicin, vincristine, and prednisone, administered on a 14-day schedule) induction, followed by positron emission tomography (PET)-guided consolidation. This post hoc analysis aimed to detail the outcomes of patients with primary mediastinal B-cell lymphoma (PMBL), verified through expert pathological review and the use of gene expression profiling (GEP) and next-generation sequencing. Of 620 centrally reviewed patients, 138 (22.3%) confirmed PMBL cases were analyzed. Baseline characteristics included a median age of 33.5 years, 63.8% female, 55.1% stage III to IV, 90.6% elevated lactate dehydrogenase, 87.6% Eastern Cooperative Oncology Group performance status score of 0 to 1, 62.3% extranodal involvement, 52.6% age-adjusted International Prognostic Index (aaIPI) of 2% to 3%, and 53.6% bulk (>10 cm). Induction regimens were R/G-CHOP14 (56.9%) and R/G-ACVBP (43.1%). Postinduction treatments, based on interim PET results, included: standard consolidation chemotherapy (59.8%) if change in maximum standardized uptake value (ΔSUVmax) of >66% after cycle 2 and >70% after cycle 4 (PET2-/4-), intensive treatment and autologous transplantation (26.8%) if PET2+/4-, and salvage therapy (13.4%) if PET4+ (ΔSUVmax of ≤70%). 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%). After a median follow-up of 39.5 months, 2-year progression-free survival (PFS) and overall survival (OS) rates were 86.2% and 93.2%, respectively. In a multivariate model including bulk, aaIPI, and ΔSUVmax PET2/PET4, only bulk and ΔSUVmax PET4 of ≤70% were associated with shorter PFS (hazard ratio, 4.39 [95% confidence interval (CI), 1.28-15.11] and 4.95 [95% CI, 1.71-14.3], respectively), whereas none were associated with OS. The ΔSUVmax-based interim PET4 response emerged as the strongest predictor of patient outcomes in this selected clinical trial population. This trial was registered at www.ClinicalTrials.gov as #NCT01659099.
Cancer Chemother Pharmacol. 2016-5
Ther Adv Med Oncol. 2024-8-28
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