Radiotherapy (RT) to bulky (B) and extralymphatic (E) disease in combination with 6xR-CHOP-14 or R-CHOP-21 in young good-prognosis DLBCL patients: Results of the 2x2 randomized UNFOLDER trial of the DSHNHL/GLA.

7574 Background: The role of RT to B and E for young patients with good-prognosis DLBCL is ill-defined. Methods: 18-60 year-old patients (aaIPI = 0 with B [≥7.5 cm], aaIPI 1) qualifying for radiotherapy to B or E were randomized to 6xR-CHOP-14 or 6x-R-CHOP-21 followed by RT (39.6 Gy) to B and E sites or observation in a 2x2 factorial design. Primary endpoint was event-free survival. Results: A planned interim analysis of the first 285 patients had revealed a significantly better EFS of patients assigned to RT (p = 0.004) resulting in the pre-defined closing of the non-RT arms. 305 pts (R-CHOP-21: 155; R-CHOP-14: 150) assigned to RT and 162 (R-CHOP-21: 81, R-CHOP-14: 81) assigned to observation were evaluable for this final analysis. There were no relevant differences in protocol adherence and toxicity between the two chemotherapy regimens. EFS, PFS and OS after R-CHOP-14 and R-CHOP-21 were not different. After 66 months median observation 3-year EFS was worse in pts not assigned to RT (68% vs. 84%; p = 0.001), due to a higher rate of PR (11% vs. 2%) triggering additional treatment (mostly RT) as an EFS event. 3-year PFS of pts assigned to RT was not significantly better (89% vs. 81%; p = 0.221) and 3-year OS (93% vs. 93%, p = 0.506) was not different, which was confirmed in a multivariate analysis adjusting for elevated LDH, stage III/IV, B and E involvement (HREFS= 0.5 [95%CI: 0.4-0.8], p = 0.001; HRPFS= 0.7 [0.5-11], p = 0.174; HROS= 1.2 [0.6-2.2], p = 0.674). Results were not different when the analysis was restricted to patients with bulky disease only. Conclusions: There were no differences in outcome between R-CHOP-14 and R-CHOP-21. Patients assigned to observation had a worse EFS because of more events largely due to a higher PR rate triggering additional treatment with no differences in PFS and OS. These results highlight the difficulties in interpreting residual masses in DLBCL without a PET which has been shown to identify (elderly) patients with B who can be spared from radiotherapy without compromising their outcome [Pfreundschuh et al., ASCO 2017, #7506]. Supported by Deutsche Krebshilfe, Amgen and Roche Clinical trial information: NCT00278408.