Held Gerhard, Thurner Lorenz, Poeschel Viola, Ott German, Schmidt Christian, Christofyllakis Konstantinos, Viardot Andreas, Borchmann Peter, Engel-Riedel Walburga, Frickhofen Norbert, Nickelsen Maike, Shpilberg Ofer, Witzens-Harig Mathias, Griesinger Frank, Krammer-Steiner Beate, Neubauer Andreas, de Nully Brown Peter, Federico Massimo, Glass Bertram, Schmitz Norbert, Wulf Gerald, Truemper Lorenz, Bewarder Moritz, Murawski Niels, Stilgenbauer Stephan, Rosenwald Andreas, Altmann Bettina, Engelhard Marianne, Schmidberger Heinz, Fleckenstein Jochen, Berdel Christian, Loeffler Markus, Ziepert Marita
Department of Internal Medicine 1, Westpfalz-Klinikum, Kaiserslautern, Germany.
Department of Internal Medicine 1 (Oncology, Hematology, Clinical Immunology and Rheumatology), Saarland University Medical School, Homburg/Saar, Germany.
Hemasphere. 2023 Jul 5;7(7):e917. doi: 10.1097/HS9.0000000000000917. eCollection 2023 Jul.
UNFOLDER (NCT00278408, EUDRACT 2005-005218-19) is a phase-3 trial in patients with aggressive B-cell lymphoma and intermediate prognosis, including primary mediastinal B-cell lymphoma (PMBCL). In a 2 × 2 factorial design, patients were randomized to 6× R-CHOP-14 or R-CHOP-21 (rituximab, cyclophosphamide, doxorubicin, vincristine, and prediso(lo)ne) and to consolidation radiotherapy to extralymphatic/bulky disease or observation. Response was assessed according to the standardized criteria from 1999, which did not include F-18 fluordesoxyglucose positron emission tomography/computed tomography (FDG-PET) scans. Primary end point was event-free survival (EFS). A subgroup of 131 patients with PMBCLs was included (median age, 34 y; 54% female, 79% elevated lactate dehydrogenase (LDH), 20% LDH >2× upper limit of normal [ULN], and 24% extralymphatic involvement). Eighty-two (R-CHOP-21: 43 and R-CHOP-14: 39) patients were assigned to radiotherapy and 49 (R-CHOP-21: 27, R-CHOP-14: 22) to observation. The 3-year EFS was superior in radiotherapy arm (94% [95% confidence interval (CI), 89-99] versus 78% [95% CI, 66-89]; = 0.0069), due to a lower rate of partial responses (PRs) (2% versus 10%). PR triggered additional treatment, mostly radiotherapy (n = 5; PR: 4; complete response/unconfirmed complete response: 1). No significant differences were observed in progression-free survival (PFS) (95% [95% CI, 90-100] versus 90% [95% CI, 81-98]; = 0.25) nor in overall survival (OS) (98% [95% CI, 94-100] versus 96% [95% CI, 90-100]; = 0.64). Comparing R-CHOP-14 and R-CHOP-21, EFS, PFS, and OS were not different. A prognostic marker for adverse outcome was elevated LDH >2× ULN (EFS: = 0.016; PFS: = 0.0049; OS: = 0.0014). With the limitation of a pre-PET-era trial, the results suggest a benefit of radiotherapy only for patients responding to R-CHOP with PR. PMBCL treated with R-CHOP have a favorable prognosis with a 3-year OS of 97%.
UNFOLDER（NCT00278408，欧盟临床试验注册号2005 - 005218 - 19）是一项针对侵袭性B细胞淋巴瘤且预后中等的患者，包括原发性纵隔B细胞淋巴瘤（PMBCL）的3期试验。采用2×2析因设计，患者被随机分为接受6周期R-CHOP-14或R-CHOP-21（利妥昔单抗、环磷酰胺、多柔比星、长春新碱和泼尼松）治疗，并接受针对结外/大块病灶的巩固放疗或观察。根据1999年的标准化标准评估反应，该标准不包括F-18氟脱氧葡萄糖正电子发射断层扫描/计算机断层扫描（FDG-PET）。主要终点是无事件生存期（EFS）。纳入了131例PMBCL患者亚组（中位年龄34岁；54%为女性，79%乳酸脱氢酶（LDH）升高，20% LDH>正常上限（ULN）的2倍，24%有结外受累）。82例（R-CHOP-21组：43例，R-CHOP-14组：39例）患者被分配接受放疗，49例（R-CHOP-21组：27例，R-CHOP-14组：22例）接受观察。放疗组的3年EFS更优（94% [95%置信区间（CI），89 - 99] 对比78% [95% CI，66 - 89]；P = 0.0069），原因是部分缓解（PR）率较低（2%对比10%）。PR引发了额外治疗，主要是放疗（n = 5；PR：4例；完全缓解/未确认完全缓解：1例）。在无进展生存期（PFS）方面未观察到显著差异（95% [95% CI，90 - 100] 对比90% [95% CI，81 - 98]；P = 0.25），总生存期（OS）方面也未观察到显著差异（98% [95% CI，94 - 100] 对比96% [95% CI，90 - 100]；P = 0.64）。比较R-CHOP-14和R-CHOP-21，EFS、PFS和OS无差异。不良预后的一个预后标志物是LDH>ULN的2倍（EFS：P = 0.016；PFS：P = 0.0049；OS：P = 0.0014）。由于该试验处于PET时代之前，结果表明放疗仅对R-CHOP治疗后出现PR的患者有益。接受R-CHOP治疗的PMBCL预后良好，3年OS为97%。
