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.
GAINED研究是一项随机3期试验，比较了奥妥珠单抗（G）与利妥昔单抗（R）加ACVBP（阿霉素、环磷酰胺和泼尼松，联合长春地辛或博来霉素）或CHOP14（环磷酰胺、阿霉素、长春新碱和泼尼松，按14天疗程给药）诱导治疗，随后进行正电子发射断层扫描（PET）引导的巩固治疗。这项事后分析旨在详细阐述经专家病理审查以及使用基因表达谱（GEP）和下一代测序验证的原发性纵隔B细胞淋巴瘤（PMBL）患者的结局。在620例经中心审查的患者中，分析了138例（22.3%）确诊的PMBL病例。基线特征包括中位年龄33.5岁，女性占63.8%，55.1%为Ⅲ至Ⅳ期，90.6%乳酸脱氢酶升高，87.6%东部肿瘤协作组体能状态评分为0至1，62.3%有结外受累，52.6%年龄校正国际预后指数（aaIPI）为2%至3%，53.6%有大包块（>10 cm）。诱导方案为R/G-CHOP14（56.9%）和R/G-ACVBP（43.1%）。根据中期PET结果进行的诱导后治疗包括：如果第2周期后最大标准化摄取值变化（ΔSUVmax）>66%且第4周期后>70%（PET2-/4-），则进行标准巩固化疗（59.8%）；如果PET2+/4-，则进行强化治疗和自体移植（26.8%）；如果PET4+（ΔSUVmax≤70%），则进行挽救治疗（13.4%）。在有GEP数据的患者（n = 107）中，38例（35.5%）为PDL1高/PDL2高。关键体细胞突变数据（n = 87）包括SOCS1（70.1%）、B2M（56.3%）、STAT6（49.4%）、TNFAIP3（47.1%）、GNA13（39.1%）、CIITA（37.9%）、CD58（36.8%）和TP53（29.9%）。中位随访39.5个月后，2年无进展生存期（PFS）和总生存期（OS）率分别为86.2%和93.2%。在一个包括大包块、aaIPI和PET2/PET4的ΔSUVmax的多变量模型中，只有大包块和PET4的ΔSUVmax≤70%与较短的PFS相关（风险比分别为4.39 [95%置信区间（CI），1.28 - 15.11]和4.95 [95% CI，1.71 - 14.3]），而与OS均无关联。在这个选定的临床试验人群中，基于ΔSUVmax的中期PET4反应是患者结局的最强预测指标。该试验已在www.ClinicalTrials.gov上注册，注册号为#NCT01659099。
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