Rituximab-CHOP With Early Rituximab Intensification for Diffuse Large B-Cell Lymphoma: A Randomized Phase III Trial of the HOVON and the Nordic Lymphoma Group (HOVON-84)

Pieternella Johanna Lugtenburg, Peter de Nully Brown, Bronno van der Holt, Francesco A D'Amore, Harry R Koene, Eva de Jongh, Rob Fijnheer, Joost W van Esser, Lara H Böhmer, Johannes F Pruijt, Gregor E Verhoef, Mels Hoogendoorn, Memis Y Bilgin, Marcel Nijland, Nicole C van der Burg-de Graauw, Margreet Oosterveld, Kon-Siong G Jie, Thomas Stauffer Larsen, Marjolein W van der Poel, Maria B LeijsMatthijs H Silbermann, Marinus van Marwijk Kooy, Aart Beker, Marie J Kersten, Jeanette K Doorduijn, Lidwine W Tick, Rolf E Brouwer, King H Lam, Coreline N Burggraaff, Bart de Keizer, Anne I Arens, Daphne de Jong, Otto S Hoekstra, Josée M Zijlstra-Baalbergen

Research output: Contribution to journalArticleAcademicpeer-review


Purpose: Immunochemotherapy with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) has become standard of care for patients with diffuse large B-cell lymphoma (DLBCL). This randomized trial assessed whether rituximab intensification during the first 4 cycles of R-CHOP could improve the outcome of these patients compared with standard R-CHOP.

Patients and methods: A total of 574 patients with DLBCL age 18 to 80 years were randomly assigned to induction therapy with 6 or 8 cycles of R-CHOP-14 with (RR-CHOP-14) or without (R-CHOP-14) intensification of rituximab in the first 4 cycles. The primary end point was complete remission (CR) on induction. Analyses were performed by intention to treat.

Results: CR was achieved in 254 (89%) of 286 patients in the R-CHOP-14 arm and 249 (86%) of 288 patients in the RR-CHOP-14 arm (hazard ratio [HR], 0.82; 95% CI, 0.50 to 1.36; P = .44). After a median follow-up of 92 months (range, 1-131 months), 3-year failure-free survival was 74% (95% CI, 68% to 78%) in the R-CHOP-14 arm versus 69% (95% CI, 63% to 74%) in the RR-CHOP-14 arm (HR, 1.26; 95% CI, 0.98 to 1.61; P = .07). Progression-free survival at 3 years was 74% (95% CI, 69% to 79%) in the R-CHOP-14 arm versus 71% (95% CI, 66% to 76%) in the RR-CHOP-14 arm (HR, 1.20; 95% CI, 0.94 to 1.55; P = .15). Overall survival at 3 years was 81% (95% CI, 76% to 85%) in the R-CHOP-14 arm versus 76% (95% CI, 70% to 80%) in the RR-CHOP-14 arm (HR, 1.27; 95% CI, 0.97 to 1.67; P = .09). Patients between ages 66 and 80 years experienced significantly more toxicity during the first 4 cycles in the RR-CHOP-14 arm, especially neutropenia and infections.

Conclusion: Early rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.
Original languageEnglish
Article number38
Pages (from-to)3377-3387
Number of pages11
JournalJournal of Clinical Oncology
Issue number29
Early online date30 Jul 2020
Publication statusPublished - 10 Oct 2020

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