Skip to main content
Top
Published in: Annals of Hematology 12/2020

01-12-2020 | Lymphoma | Original Article

First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A—results of a retrospective analysis

Authors: M. Pouyiourou, A. Meyer, A. Stroux, A. Viardot, P. La Rosée, G. Maschmeyer, D. Kämpfe, C. Kahl, V. Vucinic, A. Monecke, C. Hirt, T. Weber, J. Meissner, M. Witzens-Harig, S. Böttcher, H. Schmalenberg, R. Marks, G. Prange-Krex, F. Kroschinsky, E. Hauf, U. Keller, K. Koch, W. Klapper, M. Herold, Christian W. Scholz, on behalf of the East German Study Group for Hematology and Oncology (OSHO)

Published in: Annals of Hematology | Issue 12/2020

Login to get access

Abstract

Based on centroblast frequency, follicular lymphoma (FL) is subdivided into grades 1-2, 3A, and 3B. Grade FL3A frequently coexists with FL1-2 (FL1-2-3A). Based on clinical trials, FL1-2 is treated with rituximab (R) or obinutuzumab plus bendamustine (B) or CHOP, while FL3B is treated with R-CHOP. In contrast, there are little data guiding therapy in FL3A. We present a retrospective, multicenter analysis of 95 FL3A or FL1-2-3A and 203 FL1-2 patients treated with R-CHOP or R-B first-line. R-CHOP facilitated a higher response rate (95% versus 76%) and longer overall survival (OS) (3-year OS 89% versus 73%, P = 0.008) in FL3A or FL1-2-3A, whereas the difference in progression-free survival (PFS) did not reach statistical significance. While transformation rates into aggressive lymphoma were similar between both groups, there were more additional malignancies after R-B compared with R-CHOP (6 versus 2 cases). In FL1-2, R-B achieved a higher 3-year PFS (79% versus 47%, P < 0.01), while there was no significant difference regarding OS or transformation. With the limitations of a retrospective analysis, these results suggest a benefit for R-CHOP over R-B in FL3A or FL1-2-3A. Confirmatory data from prospective clinical trials are needed.
Appendix
Available only for authorised users
Literature
1.
go back to reference Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman J (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. In: WHO classification of tumours, Lyon. WHO reference number: 17024002. 266–279 Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri SA, Stein H, Thiele J, Vardiman J (2017) WHO classification of tumours of haematopoietic and lymphoid tissues. In: WHO classification of tumours, Lyon. WHO reference number: 17024002. 266–279
2.
go back to reference Ott G, Katzenberger T, Lohr A, Kindelberger S, Rüdiger T, Wilhelm M, Kalla J, Rosenwald A, Müller JG, Michaela Ott M, Müller-Hermelink HK (2002) Cytomorphologic, immunohistochemical, and cytogenetic profiles of follicular lymphoma: 2 types of follicular lymphoma grade 3. Blood. 99(10):3806–3812CrossRef Ott G, Katzenberger T, Lohr A, Kindelberger S, Rüdiger T, Wilhelm M, Kalla J, Rosenwald A, Müller JG, Michaela Ott M, Müller-Hermelink HK (2002) Cytomorphologic, immunohistochemical, and cytogenetic profiles of follicular lymphoma: 2 types of follicular lymphoma grade 3. Blood. 99(10):3806–3812CrossRef
3.
go back to reference Horn H, Schmelter C, Leich E, Salaverria I, Katzenberger T, Ott MM, Kalla J, Romero M, Siebert R, Rosenwald A, Ott G (2011) Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles. Haematologica. 96:1327–1334CrossRef Horn H, Schmelter C, Leich E, Salaverria I, Katzenberger T, Ott MM, Kalla J, Romero M, Siebert R, Rosenwald A, Ott G (2011) Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles. Haematologica. 96:1327–1334CrossRef
4.
go back to reference Horn H, Kohler C, Witzig R, Kreuz M, Leich E, Klapper W, Hummel M, Loeffler M, Trümper L, Spang R, Rosenwald A, Ott G (2018) Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2. Haematologica. 103(7):1182–1190CrossRef Horn H, Kohler C, Witzig R, Kreuz M, Leich E, Klapper W, Hummel M, Loeffler M, Trümper L, Spang R, Rosenwald A, Ott G (2018) Gene expression profiling reveals a close relationship between follicular lymphoma grade 3A and 3B, but distinct profiles of follicular lymphoma grade 1 and 2. Haematologica. 103(7):1182–1190CrossRef
5.
go back to reference Koch K, Hoster E, Ziepert M, Unterhalt M, Ott G, Rosenwald A, Hansmann ML, Bernd W, Stein H, Pöschel V, Dreyling M, Trümper L, Löffler M, Schmitz N, Hiddemann W, Pfreundschuh M, Klapper W (2016) Clinical, pathological and genetic features of follicular lymphoma grade 3A: a joint analysis of the German low-grade and high-grade lymphoma study groups GLSG and DSHNHL. Ann Oncol 27(7):1323–1329CrossRef Koch K, Hoster E, Ziepert M, Unterhalt M, Ott G, Rosenwald A, Hansmann ML, Bernd W, Stein H, Pöschel V, Dreyling M, Trümper L, Löffler M, Schmitz N, Hiddemann W, Pfreundschuh M, Klapper W (2016) Clinical, pathological and genetic features of follicular lymphoma grade 3A: a joint analysis of the German low-grade and high-grade lymphoma study groups GLSG and DSHNHL. Ann Oncol 27(7):1323–1329CrossRef
6.
go back to reference Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger AM, Szczepanowski M, Pott C, Kopp N, Murakami M, Horn H, Leich E, Moccia AA, Mottok A, Sunkavalli A, Van Hummelen P, Ducar M, Ennishi D, Shulha HP, Hother C, Connors JM, Sehn LH, Dreyling M, Neuberg D, Möller P, Feller AC, Hansmann ML, Stein H, Rosenwald A, Ott G, Klapper W, Unterhalt M, Hiddemann W, Gascoyne RD, Weinstock DM, Weigert O (2015) Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol 16(9):1111–1122CrossRef Pastore A, Jurinovic V, Kridel R, Hoster E, Staiger AM, Szczepanowski M, Pott C, Kopp N, Murakami M, Horn H, Leich E, Moccia AA, Mottok A, Sunkavalli A, Van Hummelen P, Ducar M, Ennishi D, Shulha HP, Hother C, Connors JM, Sehn LH, Dreyling M, Neuberg D, Möller P, Feller AC, Hansmann ML, Stein H, Rosenwald A, Ott G, Klapper W, Unterhalt M, Hiddemann W, Gascoyne RD, Weinstock DM, Weigert O (2015) Integration of gene mutations in risk prognostication for patients receiving first-line immunochemotherapy for follicular lymphoma: a retrospective analysis of a prospective clinical trial and validation in a population-based registry. Lancet Oncol 16(9):1111–1122CrossRef
7.
go back to reference Casulo C (2018) Risk stratification in follicular lymphoma. Best Pract Res Clin Haematol 31(1):15–22 Casulo C (2018) Risk stratification in follicular lymphoma. Best Pract Res Clin Haematol 31(1):15–22
8.
go back to reference Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W (2017) Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med 377(14):1331–1344CrossRef Marcus R, Davies A, Ando K, Klapper W, Opat S, Owen C, Phillips E, Sangha R, Schlag R, Seymour JF, Townsend W, Trněný M, Wenger M, Fingerle-Rowson G, Rufibach K, Moore T, Herold M, Hiddemann W (2017) Obinutuzumab for the first-line treatment of follicular lymphoma. N Engl J Med 377(14):1331–1344CrossRef
9.
go back to reference Salles G, Mounier N, De Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C (2008) Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 112:4824–4831CrossRef Salles G, Mounier N, De Guibert S, Morschhauser F, Doyen C, Rossi JF, Haioun C, Brice P, Mahé B, Bouabdallah R, Audhuy B, Ferme C, Dartigeas C, Feugier P, Sebban C, Xerri L, Foussard C (2008) Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood. 112:4824–4831CrossRef
10.
go back to reference Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE (2018) Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol 36(23):2395–2404CrossRef Hiddemann W, Barbui AM, Canales MA, Cannell PK, Collins GP, Dürig J, Forstpointner R, Herold M, Hertzberg M, Klanova M, Radford J, Seymour JF, Tobinai K, Trotman J, Burciu A, Fingerle-Rowson G, Wolbers M, Nielsen T, Marcus RE (2018) Immunochemotherapy with obinutuzumab or rituximab for previously untreated follicular lymphoma in the GALLIUM study: influence of chemotherapy on efficacy and safety. J Clin Oncol 36(23):2395–2404CrossRef
11.
go back to reference Flinn IW, Van Der Jagt R, Kahl BS, Wood P, Hawkins TE, MacDonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM (2014) Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 123(19):2944–2952CrossRef Flinn IW, Van Der Jagt R, Kahl BS, Wood P, Hawkins TE, MacDonald D, Hertzberg M, Kwan YL, Simpson D, Craig M, Kolibaba K, Issa S, Clementi R, Hallman DM, Munteanu M, Chen L, Burke JM (2014) Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study. Blood. 123(19):2944–2952CrossRef
12.
go back to reference Rummel MJ, Niederle N, Maschmeyer G, Banat GA, Von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381(9873):1203–1210. https://doi.org/10.1016/S0140-6736(12)61763-2 [Internet]CrossRefPubMed Rummel MJ, Niederle N, Maschmeyer G, Banat GA, Von Grünhagen U, Losem C, Kofahl-Krause D, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk H, Ballo H, Stauch M, Roller F, Barth J, Hoelzer D, Hinke A, Brugger W (2013) Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial. Lancet 381(9873):1203–1210. https://​doi.​org/​10.​1016/​S0140-6736(12)61763-2 [Internet]CrossRefPubMed
13.
go back to reference Roisman A, Castellano G, Navarro A, Gonzalez-Farre B, Pérez-Galan P, Esteve-Codina A, Dabad M, Heath S, Gut M, Bosio M, Bellot P, Salembier P, Oliveras A, Slavutsky I, Magnano L, Horn H, Rosenwald A, Ott G, Aymerich M, López-Guillermo A, Jares P, Martín-Subero JI, Campo E, Hernández L (2019) Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas. Br J Haematol 184(3):373–383CrossRef Roisman A, Castellano G, Navarro A, Gonzalez-Farre B, Pérez-Galan P, Esteve-Codina A, Dabad M, Heath S, Gut M, Bosio M, Bellot P, Salembier P, Oliveras A, Slavutsky I, Magnano L, Horn H, Rosenwald A, Ott G, Aymerich M, López-Guillermo A, Jares P, Martín-Subero JI, Campo E, Hernández L (2019) Differential expression of long non-coding RNAs are related to proliferation and histological diversity in follicular lymphomas. Br J Haematol 184(3):373–383CrossRef
14.
go back to reference Fisher RL, LeBlanc M, Press OW, Maloney DG, Unger JM, Miller TP (2005) New treatment options have changed the survival of patients with follicular lymphoma. J Clin Oncol 23(33):8447–52 Fisher RL, LeBlanc M, Press OW, Maloney DG, Unger JM, Miller TP (2005) New treatment options have changed the survival of patients with follicular lymphoma. J Clin Oncol 23(33):8447–52
15.
go back to reference Ladetto M, De Marco F, Benedetti F, Vitolo U, Parti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Scalabrini DR, Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C (2008) Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood 111(8):4004–13 Ladetto M, De Marco F, Benedetti F, Vitolo U, Parti C, Rambaldi A, Pulsoni A, Musso M, Liberati AM, Olivieri A, Gallamini A, Pogliani E, Scalabrini DR, Callea V, Di Raimondo F, Pavone V, Tucci A, Cortelazzo S, Levis A, Boccadoro M, Majolino I, Pileri A, Gianni AM, Passera R, Corradini P, Tarella C (2008) Prospective, multicenter randomized GITMO/IIL trial comparing intensive (R-HDS) versus conventional (CHOP-R) chemoimmunotherapy in high-risk follicular lymphoma at diagnosis: the superior disease control of R-HDS does not translate into an overall survival advantage. Blood 111(8):4004–13
16.
go back to reference Mondello P, Steiner N, Willenbacher W, Cerchione C, Nappi D, Mauro E, Ferrero S, Cuzzocrea S, Mian M (2018) Bendamustine plus rituximab versus R-CHOP as first-line treatment for patients with follicular lymphoma grade 3A: evidence from a multicenter, retrospective study. Oncologist 23(4):454–460CrossRef Mondello P, Steiner N, Willenbacher W, Cerchione C, Nappi D, Mauro E, Ferrero S, Cuzzocrea S, Mian M (2018) Bendamustine plus rituximab versus R-CHOP as first-line treatment for patients with follicular lymphoma grade 3A: evidence from a multicenter, retrospective study. Oncologist 23(4):454–460CrossRef
17.
go back to reference Shah NN, Szabo A, Saba R, Strelec L, Kodali D, Vaughn JL, Esan O, Yang DT, Mato AR, Kanate AS, Olteanu H, Hamadani M, Fenske TS, Kenkre VP, Svoboda J, Cashen AF, Epperla N (2019) Multicenter analysis of advanced stage grade 3A follicular lymphoma outcomes by frontline treatment regimen. Clin Lymphoma Myeloma Leuk 19(2):95–102 Shah NN, Szabo A, Saba R, Strelec L, Kodali D, Vaughn JL, Esan O, Yang DT, Mato AR, Kanate AS, Olteanu H, Hamadani M, Fenske TS, Kenkre VP, Svoboda J, Cashen AF, Epperla N (2019) Multicenter analysis of advanced stage grade 3A follicular lymphoma outcomes by frontline treatment regimen. Clin Lymphoma Myeloma Leuk 19(2):95–102
18.
go back to reference Steen CB, Leich E, Myklebust JH, Lockmer S, Wise JF, Wahlin BE, Østenstad B, Liestøl K, Kimby E, Rosenwald A, Smeland EB, Holte H, Lingjærde OC, Brodtkorb M (2019) A clinico-molecular predictor identifies follicular lymphoma patients at risk of early transformation after first-line immunotherapy. Haematologica. 104(10):E460–E464CrossRef Steen CB, Leich E, Myklebust JH, Lockmer S, Wise JF, Wahlin BE, Østenstad B, Liestøl K, Kimby E, Rosenwald A, Smeland EB, Holte H, Lingjærde OC, Brodtkorb M (2019) A clinico-molecular predictor identifies follicular lymphoma patients at risk of early transformation after first-line immunotherapy. Haematologica. 104(10):E460–E464CrossRef
19.
go back to reference Montoto S, Davies AJ, Matthews J, Calaminici M, Norton AJ, Amess J, Vinnicombe S, Waters R, Rohatiner AZS, Lister TA (2007) Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol 25(17):2426–2433CrossRef Montoto S, Davies AJ, Matthews J, Calaminici M, Norton AJ, Amess J, Vinnicombe S, Waters R, Rohatiner AZS, Lister TA (2007) Risk and clinical implications of transformation of follicular lymphoma to diffuse large B-cell lymphoma. J Clin Oncol 25(17):2426–2433CrossRef
20.
go back to reference Sarkozy C, Trneny M, Xerri L, Wickham N, Feugier P, Leppa S, Brice P, Soubeyran P, Da Silva MG, Mounier C, Offner F, Dupuis J, Caballero D, Canioni D, Paula M, Delarue R, Zachee P, Seymour J, Salles G, Tilly H (2016) Risk factors and outcomes for patients with follicular lymphoma who had histologic transformation after response to first-line immunochemotherapy in the PRIMA trial. J Clin Oncol 34(22):2575–82 Sarkozy C, Trneny M, Xerri L, Wickham N, Feugier P, Leppa S, Brice P, Soubeyran P, Da Silva MG, Mounier C, Offner F, Dupuis J, Caballero D, Canioni D, Paula M, Delarue R, Zachee P, Seymour J, Salles G, Tilly H (2016) Risk factors and outcomes for patients with follicular lymphoma who had histologic transformation after response to first-line immunochemotherapy in the PRIMA trial. J Clin Oncol 34(22):2575–82
21.
go back to reference Rummel MJ, Maschmeyer G, Ganser A, Heider A, von Gruenhagen U, Losem C, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk HA, Ballo H, Stauch M, Blau W, Burchardt A, Barth J, Kauff F, Brugger W (2017) Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: nine-year updated results from the StiL NHL1 study. J Clin Oncol 35:7501CrossRef Rummel MJ, Maschmeyer G, Ganser A, Heider A, von Gruenhagen U, Losem C, Heil G, Welslau M, Balser C, Kaiser U, Weidmann E, Dürk HA, Ballo H, Stauch M, Blau W, Burchardt A, Barth J, Kauff F, Brugger W (2017) Bendamustine plus rituximab (B-R) versus CHOP plus rituximab (CHOP-R) as first-line treatment in patients with indolent lymphomas: nine-year updated results from the StiL NHL1 study. J Clin Oncol 35:7501CrossRef
22.
go back to reference Flinn IW, Van Der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM (2019) First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol 37(12):984–991. https://doi.org/10.1200/JCO.18.00605 [internet]CrossRefPubMedPubMedCentral Flinn IW, Van Der Jagt R, Kahl B, Wood P, Hawkins T, MacDonald D, Simpson D, Kolibaba K, Issa S, Chang J, Trotman J, Hallman D, Chen L, Burke JM (2019) First-line treatment of patients with indolent non-Hodgkin lymphoma or mantle-cell lymphoma with bendamustine plus rituximab versus R-CHOP or R-CVP: results of the BRIGHT 5-year follow-up study. J Clin Oncol 37(12):984–991. https://​doi.​org/​10.​1200/​JCO.​18.​00605 [internet]CrossRefPubMedPubMedCentral
23.
go back to reference Jurinovic V, Passerini V, Oestergaard MZ, Knapp A, Mundt K, Araf S, Richter J, Fitzgibbon J, Klapper W, Marcus RE, Davies A, Herold M, Hiddemann W, Unterhalt M, Hoster E, Weigert O (2019) Evaluation of the m7-FLIPI in patients with follicular lymphoma treated within the Gallium trial: EZH2 mutation status may be a predictive marker for differential efficacy of chemotherapy. Blood. 134:122CrossRef Jurinovic V, Passerini V, Oestergaard MZ, Knapp A, Mundt K, Araf S, Richter J, Fitzgibbon J, Klapper W, Marcus RE, Davies A, Herold M, Hiddemann W, Unterhalt M, Hoster E, Weigert O (2019) Evaluation of the m7-FLIPI in patients with follicular lymphoma treated within the Gallium trial: EZH2 mutation status may be a predictive marker for differential efficacy of chemotherapy. Blood. 134:122CrossRef
Metadata
Title
First-line treatment with R-CHOP or rituximab-bendamustine in patients with follicular lymphoma grade 3A—results of a retrospective analysis
Authors
M. Pouyiourou
A. Meyer
A. Stroux
A. Viardot
P. La Rosée
G. Maschmeyer
D. Kämpfe
C. Kahl
V. Vucinic
A. Monecke
C. Hirt
T. Weber
J. Meissner
M. Witzens-Harig
S. Böttcher
H. Schmalenberg
R. Marks
G. Prange-Krex
F. Kroschinsky
E. Hauf
U. Keller
K. Koch
W. Klapper
M. Herold
Christian W. Scholz
on behalf of the East German Study Group for Hematology and Oncology (OSHO)
Publication date
01-12-2020
Publisher
Springer Berlin Heidelberg
Published in
Annals of Hematology / Issue 12/2020
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI
https://doi.org/10.1007/s00277-020-04171-7

Other articles of this Issue 12/2020

Annals of Hematology 12/2020 Go to the issue