Radiation and Dose‐densification of R‐CHOP in Primary Mediastinal B‐cell Lymphoma: Subgroup Analysis of the UNFOLDER Trial

• Published in: HemaSphere 2023-07, Vol.7 (7), p.e917-n/a
• Main Authors: 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, 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
• Format: Article
• Language: English
• ISSN: 2572-9241; 2572-9241
• DOI: 10.1097/HS9.0000000000000917

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]; P = 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]; P = 0.25) nor in overall survival (OS) (98% [95% CI, 94‐100] versus 96% [95% CI, 90‐100]; P = 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: P = 0.016; PFS: P = 0.0049; OS: P = 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%.