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. Bohmer, 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 Beeker, 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, Josee M. Zijlstra-Baalbergen, Aart Beker

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Abstract

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 5 .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; P5.15). 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 RRCHOP- 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
Volume38
Issue number29
Early online date30 Jul 2020
DOIs
Publication statusPublished - 10 Oct 2020

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