Rituximab maintenance improves survival in male patients with diffuse large B-cell lymphoma. Results of the HD2002 prospective multicentre randomized phase III trial

British Journal of Haematology

Volumn 171, Issue 5, 2015, Pages 710-719

  Witzens Harig, Mathias ^a   Benner, Axel ^b   McClanahan, Fabienne ^c   Klemmer, Jennifer ^a   Brandt, Julia ^a   Brants, Elke ^a   Rieger, Michael ^d   Meissner, Julia ^a   Hensel, Manfred ^e   Neben, Kai ^f   Dreger, Peter ^a   Lengfelder, Eva ^g   Schmidt Wolf, Ingo ^h   Krämer, Alwin ^a   Ho, Anthony D ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

^b GERMAN CANCER RESEARCH CENTER DKFZ   (Germany)

^c QUEEN MARY UNIVERSITY OF LONDON   (United Kingdom)

^d Onkologische Schwerpunktpraxis   (Germany)

^e Mannheimer Onkologie Praxis   (Germany)

^f Klinikum Mittelbaden   (Germany)

^g MEDICAL FACULTY MANNHEIM HEIDELBERG UNIVERSITY   (Germany)

^h UNIVERSITY OF BONN   (Germany)

Author keywords

Diffuse large B cell lymphoma; Gender differences; Multicentre prospective randomized trial; Rituximab maintenance therapy

Indexed keywords

CD20 ANTIGEN; CYCLOPHOSPHAMIDE; DOXORUBICIN; LACTATE DEHYDROGENASE; PREDNISOLONE; RITUXIMAB; VINCRISTINE; ANTINEOPLASTIC AGENT;

ABSENCE OF SIDE EFFECTS; ADULT; AGED; ARTICLE; CANCER RECURRENCE; CANCER REGRESSION; CANCER STAGING; CANCER SURVIVAL; CENTRAL NERVOUS SYSTEM DISEASE; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE SEVERITY; DRUG TOLERABILITY; DRUG WITHDRAWAL; FEBRILE LEUCOPENIA; FEMALE; FOLLOW UP; HEART DISEASE; HUMAN; INFECTION; INFUSION RELATED REACTION; INTERMETHOD COMPARISON; INTERNATIONAL PROGNOSTIC INDEX; LARGE CELL LYMPHOMA; LEUKOPENIA; LUNG DISEASE; MAINTENANCE THERAPY; MAJOR CLINICAL STUDY; MALE; METASTASIS; MULTICENTER STUDY; MULTIPLE CYCLE TREATMENT; OBSERVATIONAL STUDY; OVERALL SURVIVAL; PRIORITY JOURNAL; PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY; RANDOMIZED CONTROLLED TRIAL; RECURRENCE FREE SURVIVAL; SEX DIFFERENCE; UNSPECIFIED SIDE EFFECT; VERY ELDERLY; CLINICAL TRIAL; DRUG ADMINISTRATION; LYMPHOMA, LARGE B-CELL, DIFFUSE; MIDDLE AGED; MORTALITY; PHASE 3 CLINICAL TRIAL; PROSPECTIVE STUDY; TREATMENT OUTCOME;

ADULT; AGED; AGED, 80 AND OVER; ANTINEOPLASTIC AGENTS; DRUG ADMINISTRATION SCHEDULE; FEMALE; HUMANS; LYMPHOMA, LARGE B-CELL, DIFFUSE; MALE; MIDDLE AGED; PROSPECTIVE STUDIES; RITUXIMAB; TREATMENT OUTCOME;

EID: 84955362459     PISSN: 00071048     EISSN: 13652141     Source Type: Journal    
DOI: 10.1111/bjh.13652     Document Type: Article

References (26)

1. Carella, A.M., de Souza, C.A., Luminari, S., Marcheselli, L., Chiappella, A., di Rocco, A., Cesaretti, M., Rossi, A., Rigacci, L., Gaidano, G., Merli, F., Spina, M., Stelitano, C., Hohaus, S., Barbui, A., Puccini, B., Miranda, E.C., Guida, A. & Federico, M. (2013) Prognostic role of gender in diffuse large B-cell lymphoma treated with rituximab containing regimens: a Fondazione Italiana Linfomi/Grupo de Estudos em Moléstias Onco-Hematológicas retrospective study. Leukemia & Lymphoma, 54, 53-57.
2. Cheson, B.D., Horning, S.J., Coiffier, B., Shipp, M.A., Fisher, R.I., Connors, J.M., Lister, T.A., Vose, J., Grillo-López, A., Hagenbeek, A., Cabanillas, F., Klippensten, D., Hiddemann, W., Castellino, F., Harris, N.L., Armitage, J.O., Carter, W., Hoppe, R. & Canellos, G.P. (1999) Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas. Journal of Clinical Oncology, 17, 1244-1253.
3. Coiffier, B., Lepage, E., Briere, J., Herbrecht, R., Tilly, H., Bouabdallah, R., Morel, P., Van Den Neste, E., Salles, G., Gaulard, P., Reyes, F., Lederlin, P. & Gisselbrecht, C. (2002) CHOP chemotherapy plus rituximab compared with CHOP alone in elderly patients with diffuse large-B-cell lymphoma. New England Journal of Medicine, 346, 235-242.
4. Dietrich, S., Weidle, J., Rieger, M., Meissner, J., Radujkovic, A., Ho, A.D., Dreger, P. & Witzens-Harig, M. (2014) Rituximab maintenance therapy after autologous stem cell transplantation prolongs progression-free survival in patients with mantle cell lymphoma. Leukemia, 28, 708-709.
5. Gisselbrecht, C., Schmitz, N., Mounier, N., Singh Gill, D., Linch, D.C., Trneny, M., Bosly, A., Milpied, N.J., Radford, J., Ketterer, N., Shpilberg, O., Dührsen, U., Hagberg, H., Ma, D.D., Viardot, A., Lowenthal, R., Brière, J., Salles, G., Moskowitz, C.H. & Glass, B. (2012) Rituximab maintenance therapy after autologous stem-cell transplantation in patients with relapsed CD20(+) diffuse large B-cell lymphoma: final analysis of the collaborative trial in relapsed aggressive lymphoma. Journal of Clinical Oncology, 30, 4462-4469.
6. Grambsch, P. & Therneau, T. (1994) Proportional hazards tests and diagnostics based on weighted residuals. Biometrika, 81, 515-526.
7. Habermann, T.M., Weller, E.A., Morrison, V.A., Gascoyne, R.D., Cassileth, P.A., Cohn, J.B., Dakhil, S.R., Woda, B., Fisher, R.I., Peterson, B.A. & Horning, S.J. (2006) Rituximab-CHOP versus CHOP alone or with maintenance rituximab in older patients with diffuse large B-cell lymphoma. Journal of Clinical Oncology, 24, 3121-3127.
8. Haioun, C., Mounier, N., Emile, J.F., Ranta, D., Coiffier, B., Tilly, H., Récher, C., Fermé, C., Gabarre, J., Herbrecht, R., Morchhauser, F. & Gisselbrecht, C. (2009) Rituximab versus observation after high-dose consolidative first-line chemotherapy with autologous stem-cell transplantation in patients with poor-risk diffuse large B-cell lymphoma. Annals of Oncology, 20, 1985-1992.
9. Heinze, G. & Schemper, M. (2001) A solution to the problem of monotone likelihood in Cox regression. Biometrics, 57, 114-119.
10. Jaeger, U., Trneny, M., Melzer, H., Praxmarer, M., Fridrik, M. & Nawarawong, W. (2013) Rituximab maintenance significantly prolongs event free (EFS) and progression free survival (PFS) in male patients with aggressive B-cell lymphoma in the NHL13 study. Blood, 122, 851.
11. Jäger, U., Fridrik, M., Zeitlinger, M., Heintel, D., Hopfinger, G., Burgstaller, S., Mannhalter, C., Oberaigner, W., Porpaczy, E., Skrabs, C., Einberger, C., Drach, J., Raderer, M., Gaiger, A., Putman, M. & Greil, R.; Arbeitsgemeinschaft Medikamentöse Tumortherapie (AGMT) Investigators. (2012) Rituximab serum concentrations during immuno-chemotherapy of follicular lymphoma correlate with patient gender, bone marrow infiltration and clinical response. Haematologica, 97, 1431-1438.
12. Kluin-Nelemans, H.C., Hoster, E., Hermine, O., Walewski, J., Trneny, M., Geisler, C.H., Stilgenbauer, S., Thieblemont, C., Vehling-Kaiser, U., Doorduijn, J.K., Coiffier, B., Forstpointner, R., Tilly, H., Kanz, L., Feugier, P., Szymczyk, M., Hallek, M., Kremers, S., Lepeu, G., Sanhes, L., Zijlstra, J.M., Bouabdallah, R., Lugtenburg, P.J., Macro, M., Pfreundschuh, M., Procházka, V., Di Raimondo, F., Ribrag, V., Uppenkamp, M., André, M., Klapper, W., Hiddemann, W., Unterhalt, M. & Dreyling, M.H. (2012) Treatment of older patients with mantle-cell lymphoma. New England Journal of Medicine, 367, 520-531.
13. Kosmas, C., Stamatopoulos, K., Stavroyianni, N., Tsavaris, N. & Papadaki, T. (2002) Anti-CD20-based therapy of B cell lymphoma: state of the art. Leukemia, 16, 2004-2015.
14. Ladetto, M., Zallio, F., Vallet, S., Ricca, I., Cuttica, A., Caracciolo, D., Corradini, P., Astolfi, M., Sametti, S., Volpato, F., Bondesan, P., Vitolo, U., Boccadoro, M., Pileri, A., Gianni, A.M. & Tarella, C. (2012) Concurrent administration of high-dose chemotherapy and rituximab is a feasible and effective chemo/immunotherapy for patients with high-risk non-Hodgkin's lymphoma. Leukemia, 15, 1941-1949.
15. Moher, D., Schulz, K.F. & Altman, D.G. (2001) The CONSORT statement: revised recommendations for improving the quality of reports of parallel-group randomised trials. Lancet, 357, 1191-1194.
16. Müller, C., Murawski, N., Wiesen, M.H., Held, G., Poeschel, V., Zeynalova, S., Wenger, M., Nickenig, C., Peter, N., Lengfelder, E., Metzner, B., Rixecker, T., Zwick, C., Pfreundschuh, M. & Reiser, M. (2012) The role of sex and weight on rituximab clearance and serum elimination half-life in elderly patients with DLBCL. Blood, 119, 3276-3284.
17. van Oers, M.H., Klasa, R., Marcus, R.E., Wolf, M., Kimby, E., Gascoyne, R.D., Jack, A., Van't Veer, M., Vranovsky, A., Holte, H., van Glabbeke, M., Teodorovic, I., Rozewicz, C. & Hagenbeek, A. (2006) Rituximab maintenance improves clinical outcome of relapsed/resistant follicular non-Hodgkin lymphoma in patients both with and without rituximab during induction: results of a prospective randomized phase 3 intergroup trial. Blood, 108, 3295-3301.
18. Pfreundschuh, M., Schubert, J., Ziepert, M., Schmits, R., Mohren, M., Lengfelder, E., Reiser, M., Nickenig, C., Clemens, M., Peter, N., Bokemeyer, C., Eimermacher, H., Ho, A., Hoffmann, M., Mertelsmann, R., Trümper, L., Balleisen, L., Liersch, R., Metzner, B., Hartmann, F., Glass, B., Poeschel, V., Schmitz, N., Ruebe, C., Feller, A.C. & Loeffler, M.; German High-Grade Non-Hodgkin Lymphoma Study Group (DSHNHL). (2008) Six versus eight cycles of bi-weekly CHOP-14 with or without rituximab in elderly patients with aggressive CD20+ B-cell lymphomas: a randomised controlled trial (RICOVER-60). The Lancet. Oncology, 9, 105-116.
19. Pfreundschuh, M., Müller, C., Zeynalova, S., Kuhnt, E., Wiesen, M.H., Held, G., Rixecker, T., Poeschel, V., Zwick, C., Reiser, M., Schmitz, N. & Murawski, N. (2014) Suboptimal dosing of rituximab in male and female patients with DLBCL. Blood, 123, 640-646.
20. R Core Team. (2015) R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria.
21. Riihijärvi, S., Taskinen, M., Jerkeman, M. & Leppä, S. (2011) Male gender is an adverse prognostic factor in B-cell lymphoma patients treated with immunochemotherapy. European Journal of Haematology, 86, 124-128.
22. Saito, B., Shiozawa, E., Usui, T., Nakashima, H., Maeda, T., Hattori, N., Shimozuma, J., Adachi, D., Yamochi-Onizuka, T., Takimoto, M., Nakamaki, T., Ota, H. & Tomoyasu, S. (2007) Rituximab with chemotherapy improves survival of non-germinal center type untreated diffuse large B-cell lymphoma. Leukemia, 21, 2563-2566.
23. Salles, G., Seymour, J.F., Offner, F., López-Guillermo, A., Belada, D., Xerri, L., Feugier, P., Bouabdallah, R., Catalano, J.V., Brice, P., Caballero, D., Haioun, C., Pedersen, L.M., Delmer, A., Simpson, D., Leppa, S., Soubeyran, P., Hagenbeek, A., Casasnovas, O., Intragumtornchai, T., Fermé, C., daSilva, M.G., Sebban, C., Lister, A., Estell, J.A., Milone, G., Sonet, A., Mendila, M., Coiffier, B. & Tilly, H. (2011) Rituximab maintenance for 2 years in patients with high tumour burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomised controlled trial. Lancet, 377, 42-51.
24. Schemper, M. & Smith, T.L. (1996) A note on quantifying follow-up in studies of failure time. Controlled Clinical Trials, 17, 343-346.
25. Tarella, C., Zanni, M., Di Nicola, M., Patti, C., Calvi, R., Pescarollo, A., Zoli, V., Fornari, A., Novero, D., Cabras, A., Stella, M., Comino, A., Remotti, D., Ponzoni, M., Caracciolo, D., Ladetto, M., Magni, M., Devizzi, L., Rosato, R., Boccadoro, M., Bregni, M., Corradini, P., Gallamini, A., Majolino, I., Mirto, S. & Gianni, A.M.; Gruppo Italiano Terapie Innovative nei Linfomi. (2007) Prolonged survival in poor-risk diffuse large B-cell lymphoma following front-line treatment with rituximab-supplemented, early-intensified chemotherapy with multiple autologous hematopoietic stem cell support: a multicenter study by GITIL (Gruppo Italiano Terapie Innovative nei Linfomi). Leukemia, 21, 1802-1811.
26. Vellenga, E., van Putten, W.L., van 't Veer, M.B., Zijlstra, J.M., Fibbe, W.E., van Oers, M.H., Verdonck, L.F., Wijermans, P.W., van Imhoff, G.W., Lugtenburg, P.J. & Huijgens, P.C. (2008) Rituximab improves the treatment results of DHAP-VIM-DHAP and ASCT in relapsed/progressive aggressive CD20+ NHL: a prospective randomized HOVON trial. Blood, 111, 537-543.