Due to the assessment of computerized tomography with criteria from 1999, the role of radiotherapy in patients with diffuse large B-cell lymphoma with bulky or extranodal disease remains undefined.
Investigators found that adding consolidation radiotherapy for aggressive B-cell lymphoma can improve event-free survival (EFS) without affecting progression-free survival (PFS) or overall survival, according to the results of a study published by Hemasphere.
Although the EFS was improved with radiotherapy, investigators did say that radiation was largely unplanned in the observation-arm due to the lack of complete responses (CRs). Because of the assessment of computerized tomography with criteria from 1999, the role of radiotherapy in patients with diffuse large B-cell lymphoma (DLBCL) with bulky or extranodal disease remains undefined, according to the authors of the UNFOLDER study (NCT00278408).
The international phase 3 study is enrolled individuals aged 18 through 60 years with aggressive B-cell lymphoma and an intermediate prognosis by the age-adjusted International Prognostic Index score of 0 and bulky disease score of 1. The study included data from 148 clinical sites across Denmark, Israel, Italy, and Germany.
There were 695 individuals included in the intention-to-treat analysis from January 2, 2006, to November 16, 2015.
Individuals enrolled in the study received rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2, doxorubicin at 50 mg/m2, vincristine at 1.4 mg/m2 with a maximum total dose of 2 mg (R-CHOP), which was administered on day 1 with oral prednisone or prednisolone at 100 mg on days 1 through 5.
Individuals were randomized to receive either R-CHOP-14 every 2 weeks with a mandatory granulocyte colony-stimulating factor-support or R-CHOP-21 every 3 weeks.
Investigators did not plan on administering radiotherapy for bone marrow, lung, liver, kidney, small intestine, colon, ascites, pericardial, and pleural effusions. Radiotherapy was administered at a total dose of 39.6 Gy with 1.8 Gy/fraction 5 times a week, starting 2 to 6 weeks after chemotherapy.
Approximately 89% of the individuals had DLBCL or one of its subtypes, according to the investigators. There were no relevant differences in adherence and dose-achievement between R-CHOP-21 and R-CHOP-14, and 88% of individuals randomized in the radiotherapy arm received radiotherapy as per the protocol.
A total of 467 individuals received radiotherapy. In the planned interim analysis of the first 285 individuals, investigators found “a slightly better EFS for patients assigned to radiotherapy, resulting in a predefined closing of the observation-arms with 305 individuals assigned to radiotherapy and 162 to observation.”
Investigators found that in the final response assessment, 90% of individuals in the radiotherapy-arm had a CR or CR unconfirmed compared with 79% in the observation arm. However, the rate of partial response (PR) in the radiotherapy-arm was 2% compared to 11% in the observation-arm.
After a median observation of 66 months, the 3-year EFS was 84% with the radiotherapy arm compared to the observation arm at 68%. Investigators said that the difference was caused by the lower rate of PR, which triggered additional treatment and resulted in radiotherapy in the observational arm. Additionally, after 3 years, there was no statistical difference in PFS between radiotherapy at 89% and 81%, respectively. The OS was 93% in both arms.
Investigators determined that dose-densification of either R-CHOP-21 and R-CHOP-14 did not improve treatment for young individuals with B-cell lymphoma and an intermediate risk profile
Thurner L, Ziepert M, Berdel C, Schmidt C, et al. Radiation and dose-densification of R-CHOP in Aggressive B-cell lymphoma with intermediate prognosis: the UNFOLDER study. Hemasphere. 2023;7(7):e904. doi:10.1097/HS9.0000000000000904