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781 Excellent Outcome of Young Patients (18-60 years) with Favourable-Prognosis Diffuse Large B-Cell Lymphoma (DLBCL) Treated with 4 Cycles CHOP Plus 6 Applications of Rituximab: Results of the 592 Patients of the Flyer Trial of the Dshnhl/GLAClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)—Results from Prospective Clinical Trials: Initial Treatment
Hematology Disease Topics & Pathways:
Adult, Diseases, Lymphoma (any), Therapies, DLBCL, Non-Hodgkin Lymphoma, B-Cell Lymphoma, Young Adult, Study Population, Clinically relevant, Lymphoid Malignancies
Monday, December 3, 2018: 2:45 PM
Ballroom 20A (San Diego Convention Center)

Viola Poeschel, MD1*, Gerhard Held, MD1*, Marita Ziepert, PhD2*, Bettina Altmann, PhD§2*, Mathias Witzens-Harig, MD3*, Harald Holte, MD, PhD4, Lorenz Thurner, MD5*, Andreas Viardot, MD6, Peter Borchmann, MD7, Lothar Kanz8, Ulrich Keller9*, Christian Schmidt, MD10*, Rolf Mahlberg, MD11*, Bernd Metzner, MD, PhD12, Reinhard Marks13*, Heinz-Gert Hoeffkes, MD14*, Konstantinos Christofyllakis, MD15*, Josif Amam1*, Christian Berdel, MD16*, Stephan Stilgenbauer, MD15, Norbert Schmitz, MD17*, Lorenz Truemper, MD18, Niels Murawski, MD1*, Markus Loeffler, MD19* and Michael Pfreundschuh, MD1

1Department of hematology, oncology and rheumatology, Saarland University Medical School, Homburg/Saar, Germany
2Institute for Medical Informatics, Statistics and Epidemiology, University Leipzig, Leipzig, Germany
3Department of Internal Medicine V, University of Heidelberg, Heidelberg, Germany
4Oslo University Hospital, Oslo, Norway
5Department of hematology, oncology and rheumatology and José Carreras Center for Immuno and Gene therapy, Saarland University Medical School, Homburg/Saar, Germany
6Department of Internal Medicine III, University Hospital Ulm, Ulm, Germany
7Department of Haematology and Oncology, University Hospital of Cologne, Cologne, Germany
8University Hospital Tuebingen, Tuebingen, Germany
9Klinikum Rechts der Isar der TU München, Munchen, Germany
10Department of Medicine III, University Hospital, LMU Munich, Munich, Germany
11Klinikum Mutterhaus der Borromraeerinnen, Trier, Germany
12Klinikum Oldenburg, Oldenburg, Germany
13Department of Hematology and Oncology, University Medical Center, Freiburg, Germany
14Klinikum Fulda Tumorklinik, Fulda, Germany
15Department of Hematology, Oncology, Rheumatology and Clinical Immunology, Saarland University Medical Center, Homburg, Germany
16Department of radiooncology, Saarland University Medical School, Homburg/Saar, Germany
17Medizinische Klinik A, University Hospital Münster, Münster, Germany
18Georg August University, Goettingen, Germany
19Institute for Medical Informatics, Statistics and Epidemiology, Leipzig University, Faculty of Medicine, IMISE, Leipzig, Germany

Background: 6 cycles CHOP-like chemotherapy plus rituximab (6x R-CHOP) are the standard treatment for young patients with DLBCL. The MInT trial established a subgroup with favourable prognosis as defined as aaIPI=0 and no bulky disease [Pfreundschuh et al., Lancet Oncol 2006; 7: 379-391] with a 3-year EFS of 89%, PFS of 95% and OS of 98%. We hypothesized that 4 cycles of CHOP plus 6 applications of rituximab are non-inferior to the standard treatment of 6x R-CHOP in this population.

Patients and Methods: 18 to 60 year-old patients, aaIPI =0 without bulky (≥7.5 cm) disease were randomized to receive 6x R-CHOP or 4x R-CHOP+2xR at 21-day cycles. Radiotherapy was not planned to be given except for prophylactic radiotherapy of the contralateral testis in patients with testicular lymphoma. The primary endpoint was progression free survival (PFS) with events defined as progressive disease, relapse or death. Assuming a 93% 3-years PFS for the 6x R-CHOP arm, it was planned to tolerate an impairment of 5.5% by reducing the number of courses to 4x R-CHOP+2xR to prove non-inferiority with a power of 80% and an alpha-error of 5% (one-sided).

Results: Between 12/2005 and 10/2016, 592 patients were randomized in the international multi-center FLYER trial and 588 patients were evaluable for this final analysis. 295 patients were assigned to receive 6x R-CHOP and 293 were assigned to receive 4x R-CHOP+2xR. There were no relevant differences in demographics (median age: 48 years, 99% aaIPI=0, 1% aaIPI=1, 0.3% bulky disease), protocol adherence and toxicity between the two arms.

PFS, EFS and OS after 4x R-CHOP+2xR were as good as after 6x R-CHOP. After 66 months median observation, the 3-year PFS rate of the patients receiving 4x R-CHOP+2xR was 96% vs. 94% of patients receiving 6x R-CHOP (p=0.760). The lower limit of the 95% CI of the difference between treatment arms was 0% and excludes -5.5% demonstrating the non-inferiority. The 3-year EFS was identical (89%) in both treatment arms. The 3-years OS was 99% in patients receiving 4x R-CHOP+2xR and 98% in patients receiving 6x R-CHOP. In a multivariable analysis adjusting for strata (stage and E-involvement), the hazard ratio of 4x R-CHOP+2xR compared to 6x R-CHOP was 1.0 (95% CI: 0.7-1.6; p=0.896) for EFS, 0.9 (95% CI: 0.5-1.6; p=0.797) for PFS, and 0.8 (95% CI: 0.4-1.9; p=0.671) for OS. With respect to relapse rate there was also no significant difference between the two treatment arms. 4% (95% CI 2-7%) of the patients in the 4x R-CHOP+2xR arm relapsed vs. 5% (95% CI 3-8%) of the patients in the 6x R-CHOP arm. 33% of relapses occurred in the first two years after study inclusion but continue to be seen with longer follow-up in both arms.

Conclusion: In young patients with favourable prognosis DLBCL outcome after 4x R-CHOP+ 2xR is non-inferior compared to the previous standard 6x R-CHOP. Thus, chemotherapy can be spared without compromising prognosis in this population. Supported by Deutsche Krebshilfe

Disclosures: Poeschel: Roche: Other: Travel grants; Amgen: Other: Travel grants. Held: BMS: Consultancy, Other: Travel grants, Research Funding; Amgen: Research Funding; Roche: Consultancy, Other: Travel grants, Research Funding; MSD: Consultancy; Spectrum: Research Funding. Holte: Roche, Norway: Research Funding; Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees. Viardot: Roche: Consultancy, Honoraria; Amgen: Consultancy; Gilead Kite: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria. Borchmann: Novartis: Consultancy, Honoraria. Keller: Celgene: Research Funding; BMS: Consultancy; Takeda: Consultancy, Research Funding; Janssen-Cilag: Consultancy, Equity Ownership; Roche: Consultancy; MSD: Consultancy. Schmidt: Gilead: Honoraria, Other: Travel Grants; Celgene: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel Grants. Marks: Merck: Honoraria; BMS: Honoraria; Servier: Honoraria. Stilgenbauer: Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Genzyme: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer-Ingelheim: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pharmcyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Mundipharma: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Hoffmann La-Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Schmitz: Riemser: Honoraria, Other: Travel grants; Kite/Gilead: Honoraria, Other: Travel grants; Novartis: Honoraria, Other: Travel grants; Celgene: Other: Travel grants; Roche: Honoraria. Murawski: Takeda: Consultancy; Janssen: Other: Travel grants.

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