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)

• DOI: 10.1200/jco.19.03418
• Publication Date: 2020-07-30T20:02:31Z
• Authors: Pieternella Johan...; 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...; Margreet Oosterveld; Kon-Siong G. Jie; Thomas Stauffer L...; Marjolein W. van ...; Maria B. Leijs; Matthijs H. Silbe...; Marinus van Marwi...; Aart Beeker; Marie J. Kersten; Jeanette K. Doord...; Lidwine W. Tick; Rolf E. Brouwer; King H. Lam; Coreline N. Burgg...; Bart de Keizer; Anne I. Arens; Daphne de Jong; Otto S. Hoekstra; Josée M. Zijlstra...
• Keywords: Male; 0301 basic medicine; Cancer Research; chemotherapy; Positron Emission Tomography Computed Tomography; Medical Imaging - Radboud University Medical Center; Antineoplastic Combined Chemotherapy Protocols; ELDERLY-PATIENTS; response assessment; Aged, 80 and over; DOSE-DENSE RITUXIMAB; dose-dense rituximab; Induction Chemotherapy; CHEMOTHERAPY; Middle Aged; EMC NIHES-03-30-02; 3. Good health; Treatment Outcome; Oncology; Vincristine; Female; Lymphoma, Large B-Cell, Diffuse; NON-HODGKIN-LYMPHOMA; Rituximab; optimization; Adult; DOXORUBICIN; Adolescent; Radboud University Medical Center; plus cyclophosphamide; elderly-patients; doxorubicin; vincristine; PLUS CYCLOPHOSPHAMIDE; Maintenance Chemotherapy; 03 medical and health sciences; Journal Article; Humans; non-hodgkin-lymphoma; VINCRISTINE; EXPOSURE; OPTIMIZATION; Cyclophosphamide; Aged; Radboudumc 9: Rare cancers RIHS: Radboud Institute for Health Sciences; EMC MM-03-24-01; exposure; Doxorubicin; Prednisone; RESPONSE ASSESSMENT; Follow-Up Studies

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.