Pieternella Johanna Lugtenburg1, Peter de Nully Brown2, Bronno van der Holt3, Francesco A D'Amore4, Harry R Koene5, Eva de Jongh6, Rob Fijnheer7, Joost W van Esser8, Lara H Böhmer9, Johannes F Pruijt10, Gregor E Verhoef11, Mels Hoogendoorn12, Memis Y Bilgin13, Marcel Nijland14, Nicole C van der Burg-de Graauw15, Margreet Oosterveld16, Kon-Siong G Jie17, Thomas Stauffer Larsen18, Marjolein W van der Poel19, Maria B Leijs20, Matthijs H Silbermann21, Marinus van Marwijk Kooy22, Aart Beeker23, Marie J Kersten24, Jeanette K Doorduijn1, Lidwine W Tick25, Rolf E Brouwer26, King H Lam1, Coreline N Burggraaff27, Bart de Keizer28, Anne I Arens29, Daphne de Jong30, Otto S Hoekstra27, Josée M Zijlstra-Baalbergen27. 1. Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 2. Rigshospitalet Copenhagen University Hospital, Copenhagen, Denmark. 3. Haemato Oncology Foundation for Adults in the Netherlands (HOVON) Data Center, Erasmus MC Cancer Institute, Rotterdam, the Netherlands. 4. Aarhus University Hospital, Aarhus, Denmark. 5. St Antonius Hospital, Nieuwegein, the Netherlands. 6. Albert Schweitzer Hospital, Dordrecht, the Netherlands. 7. Meander MC, Amersfoort, the Netherlands. 8. Amphia Hospital, Breda, the Netherlands. 9. Haga Teaching Hospital, The Hague, the Netherlands. 10. Jeroen Bosch Hospital, 's Hertogenbosch, the Netherlands. 11. University Hospitals Leuven, Leuven, Belgium. 12. Medical Center Leeuwarden, Leeuwarden, the Netherlands. 13. Admiraal de Ruijter Hospital, Goes, the Netherlands. 14. University Medical Center Groningen, Groningen, the Netherlands. 15. Bravis Hospital, Roosendaal, the Netherlands. 16. Canisius Wilhelmina Hospital, Nijmegen, the Netherlands. 17. Zuyderland Medical Center, Heerlen, the Netherlands. 18. Odense University Hospital, Odense, Denmark. 19. Maastricht University MC, Maastricht, the Netherlands. 20. Maasstad Hospital, Rotterdam, the Netherlands. 21. Tergooi Hospitals, Hilversum, the Netherlands. 22. Isala Hospital, Zwolle, the Netherlands. 23. Spaarne Gasthuis, Hoofddorp, the Netherlands. 24. Amsterdam UMC, AMC, Amsterdam, the Netherlands. 25. Maxima Medical Center, Eindhoven, the Netherlands. 26. Reinier de Graaf Hospital, Delft, the Netherlands. 27. Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands. 28. UMC Utrecht, Utrecht, the Netherlands. 29. Radboud UMC, Nijmegen, the Netherlands. 30. HOVON Pathology Facility and Biobank, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
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 age18 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.
RCT Entities:
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.
Authors: J J Eertink; C N Burggraaff; M W Heymans; U Dührsen; A Hüttmann; C Schmitz; S Müller; P J Lugtenburg; S F Barrington; N G Mikhaeel; R Carr; S Czibor; T Györke; L Ceriani; E Zucca; M Hutchings; L Kostakoglu; A Loft; S Fanti; S E Wiegers; S Pieplenbosch; R Boellaard; O S Hoekstra; J M Zijlstra; H C W de Vet Journal: Blood Adv Date: 2021-05-11
Authors: Gerben J C Zwezerijnen; Jakoba J Eertink; Maria C Ferrández; Sanne E Wiegers; Coreline N Burggraaff; Pieternella J Lugtenburg; Martijn W Heymans; Henrica C W de Vet; Josée M Zijlstra; Ronald Boellaard Journal: Eur J Nucl Med Mol Imaging Date: 2022-09-27 Impact factor: 10.057
Authors: Coreline N Burggraaff; Jakoba J Eertink; Pieternella J Lugtenburg; Otto S Hoekstra; Anne I J Arens; Bart de Keizer; Martijn W Heymans; Bronno van der Holt; Sanne E Wiegers; Simone Pieplenbosch; Ronald Boellaard; Henrica C W de Vet; Josée M Zijlstra Journal: J Nucl Med Date: 2021-10-21 Impact factor: 11.082
Authors: N George Mikhaeel; Martijn W Heymans; Jakoba J Eertink; Henrica C W de Vet; Ronald Boellaard; Ulrich Dührsen; Luca Ceriani; Christine Schmitz; Sanne E Wiegers; Andreas Hüttmann; Pieternella J Lugtenburg; Emanuele Zucca; Gerben J C Zwezerijnen; Otto S Hoekstra; Josée M Zijlstra; Sally F Barrington Journal: J Clin Oncol Date: 2022-03-31 Impact factor: 50.717
Authors: L Hounsome; T A Eyre; R Ireland; A Hodson; R Walewska; K Ardeshna; S Chaganti; P McKay; A Davies; C P Fox; N Kalakonda; P A Fields Journal: Br J Cancer Date: 2021-10-05 Impact factor: 7.640
Authors: Gerben J C Zwezerijnen; Jakoba J Eertink; Coreline N Burggraaff; Sanne E Wiegers; Ekhlas A I N Shaban; Simone Pieplenbosch; Daniela E Oprea-Lager; Pieternella J Lugtenburg; Otto S Hoekstra; Henrica C W de Vet; Josee M Zijlstra; Ronald Boellaard Journal: J Nucl Med Date: 2021-03-05 Impact factor: 11.082
Authors: Jakoba J Eertink; Elisabeth A G Pfaehler; Sanne E Wiegers; Tim van; Pieternella J Lugtenburg; Otto S Hoekstra; Josée M Zijlstra; Henrica C W de Vet; Ronald Boellaard Journal: J Nucl Med Date: 2021-07-16 Impact factor: 10.057