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)

P.J. Lugtenburg*, P.D. Brown, B. van der Holt, F.A. D'Amore, H.R. Koene, E. de Jongh, R. Fijnheer, J.W. van Esser, L.H. Bohmer, J.F. Pruijt, G.E. Verhoef, M. Hoogendoorn, M.Y. Bilgin, M. Nijland, N.C. van der Burg-de Graauw, M. Oosterveld, K.S.G. Jie, T.S. Larsen, M.W. van der Poel, M.B. LeijsM.H. Silbermann, M.V. Kooy, A. Beeker, M.J. Kersten, J.K. Doorduijn, L.W. Tick, R.E. Brouwer, K.H. Lam, C.N. Burggraaff, B. de Keizer, A.I. Arens, D. de Jong, O.S. Hoekstra, J.M. Zijlstra-Baalbergen

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

24 Citations (Web of Science)


PURPOSEImmunochemotherapy 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 METHODSA 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.RESULTSCR 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.CONCLUSIONEarly rituximab intensification during R-CHOP-14 does not improve outcome in patients with untreated DLBCL.
Original languageEnglish
Number of pages18
JournalJournal of Clinical Oncology
Issue number29
Publication statusPublished - 10 Oct 2020


  • chemotherapy
  • dose-dense rituximab
  • doxorubicin
  • elderly-patients
  • exposure
  • non-hodgkin-lymphoma
  • optimization
  • plus cyclophosphamide
  • response assessment
  • vincristine

Cite this