Rituximab plus Lenalidomide in Advanced Untreated Follicular Lymphoma

被引：299

作者：

Morschhauser, F. ^{[1
]}

Fowler, N. H. ^{[20
]}

Feugier, P. ^{[2
]}

Bouabdallah, R. ^{[3
]}

Tilly, H. ^{[5
,6
]}

Palomba, M. L. ^{[21
]}

Fruchart, C. ^{[7
]}

Libby, E. N. ^{[22
]}

Casasnovas, R-O. ^{[8
]}

Flinn, I. W. ^{[23
]}

Haioun, C. ^{[9
]}

Maisonneuve, H. ^{[10
]}

Ysebaert, L. ^{[11
]}

Bartlett, N. L. ^{[24
]}

Bouabdallah, K. ^{[12
]}

Brice, P. ^{[13
]}

Ribrag, V. ^{[14
]}

Daguindau, N. ^{[15
]}

Le Gouill, S. ^{[16
]}

Pica, G. M. ^{[17
]}

Martin Garcia-Sancho, A. ^{[25
,26
]}

Lopez-Guillermo, A. ^{[27
]}

Larouche, J-F. ^{[28
]}

Ando, K. ^{[30
]}

Gomes da Silva, M. ^{[31
]}

Andre, M. ^{[32
]}

Zachee, P. ^{[33
]}

Sehn, L. H. ^{[29
]}

Tobinai, K. ^{[34
]}

Cartron, G. ^{[18
]}

Liu, D. ^{[35
]}

Wang, J. ^{[35
]}

Xerri, L. ^{[4
]}

Salles, G. A. ^{[19
]}

机构：

[1] Univ Lille, CHU, Grp Rech Formes Injectables & Technol Associees, Lille, France

[2] CHU Reg Nancy, Serv Hematol, Vandoeuvre Les Nancy, France

[3] Inst Paoli Calmettes, Marseille, France

[4] Aix Marseille Univ, Ctr Rech Cancerol Marseille, CNRS, Dept Pathol,Inst Paoli Calmettes,INSERM, Marseille, France

[5] Univ Rouen, Ctr Henri Becquerel, U1245, Rouen, France

[6] Univ Rouen, Dept Hematol, Rouen, France

[7] Inst Hematol Basse Normandie, Caen, France

[8] CHU Bocage, Serv Hematol Clin, Dijon, France

[9] Hop Henri Mondor, Unite Hemopathies Lymphoides, Creteil, France

[10] Ctr Hosp Dept Vendee, Serv Oncohematol, La Roche Sur Yon, France

[11] Inst Univ Canc Toulouse Oncopole, Serv Hematol, Toulouse, France

[12] CHU Bordeaux, Serv Hematol, Bordeaux, France

[13] Hop St Louis, Serv Oncohematol, Paris, France

[14] Gustave Roussy Canc, Villejuif, France

[15] Ctr Hosp Annecy Genevois Serv, Annecy, France

[16] Univ Nantes, Ctr Rech Cancerol & Immunol, CNRS, Hotel Dieu,Serv Hematol Clin,INSERM, Nantes, France

[17] Ctr Hosp Metropole Savoie, Serv Hematol, Chambery, France

[18] Univ Montpellier, CHU Montpellier, Dept Hematol, Montpellier, France

[19] Univ Lyon, Ctr Hosp Lyon Sud, Hosp Civils Lyon, Pierre Benite, France

[20] Univ Texas MD Anderson Canc Ctr, Dept Lymphoma & Myeloma, Houston, TX 77030 USA

[21] Mem Sloan Kettering Canc Ctr, Dept Med, 1275 York Ave, New York, NY 10021 USA

[22] Univ Washington, Dept Med, Div Med Oncol, Seattle, WA USA

[23] Tennessee Oncol, Sarah Cannon Res Inst, Nashville, TN USA

[24] Washington Univ, Sch Med, Siteman Canc Ctr, St Louis, MO USA

[25] Hosp Univ Salamanca, Dept Hematol, Salamanca, Spain

[26] Ctr Invest Biomed Red Canc, Inst Invest Biomed Salamanca, Salamanca, Spain

[27] Hosp Clin Barcelona, Dept Hematol, Barcelona, Spain

[28] CHU Quebec, Hop Enfant Jesus, Quebec City, PQ, Canada

[29] Univ British Columbia, British Columbia Canc Ctr Lymphoid Canc, Vancouver, BC, Canada

[30] Tokai Univ Hosp, Dept Hematol & Oncol, Isehara, Kanagawa, Japan

[31] Inst Portugues Oncol Francisco Gentil, Dept Hematol, Lisbon, Portugal

[32] Univ Catholique Louvain Namur, CHU, Dept Hematol, Yvoir, Belgium

[33] Ziekenhuis Netwerk Antwerpen Stuivenberg, Dept Hematol, Antwerp, Belgium

[34] Natl Canc Ctr, Dept Hematol, Tokyo, Japan

[35] Celgene, Summit, NJ USA

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2018年 / 379卷 / 10期

关键词：

MANTLE CELL LYMPHOMA; 1ST-LINE TREATMENT; OPEN-LABEL; INDOLENT; IKAROS; IMMUNOCHEMOTHERAPY; POMALIDOMIDE; DEGRADATION; PHASE-3; AIOLOS;

D O I：

10.1056/NEJMoa1805104

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Rituximab plus chemotherapy has been shown to be effective in patients with advanced-stage, previously untreated follicular lymphoma; nevertheless, most patients will have a relapse. Combination immunotherapy with lenalidomide and rituximab is an immunomodulatory regimen that has shown promising activity in patients with indolent B-cell non-Hodgkin's lymphoma. METHODS We conducted this multicenter, international, phase 3 superiority trial to evaluate rituximab plus lenalidomide, as compared with rituximab plus chemotherapy, in patients with previously untreated follicular lymphoma. Patients were randomly assigned to receive one of the two regimens, followed by maintenance monotherapy with rituximab. Treatment with rituximab plus lenalidomide consisted of 18 cycles of the two drugs, followed by rituximab maintenance therapy every 8 weeks for 12 cycles (six additional doses). Treatment with rituximab plus chemotherapy consisted of the investigator's choice of one of three rituximab-based regimens, followed by maintenance monotherapy with rituximab every 8 weeks for 12 cycles. The primary end points were complete response (confirmed or unconfirmed) at 120 weeks and progression-free survival. RESULTS A total of 1030 patients were randomly assigned to receive rituximab plus lenalidomide (513 patients) or rituximab plus chemotherapy (517 patients). The rate of confirmed or unconfirmed complete response at 120 weeks was similar in the two groups: 48% (95% confidence interval [CI], 44 to 53) in the rituximab-lenalidomide group and 53% (95% CI, 49 to 57) in the rituximab-chemotherapy group (P = 0.13). The interim 3-year rate of progression-free survival was 77% (95% CI, 72 to 80) and 78% (95% CI, 74 to 82), respectively. A higher percentage of patients in the rituximabchemotherapy group had grade 3 or 4 neutropenia (32% vs. 50%) and febrile neutropenia of any grade (2% vs. 7%), and a higher percentage of patients in the rituximab-lenalidomide group had grade 3 or 4 cutaneous reactions (7% vs. 1%). CONCLUSIONS Among patients with previously untreated follicular lymphoma, efficacy results were similar with rituximab plus lenalidomide and rituximab plus chemotherapy (with both regimens followed by rituximab maintenance therapy). The safety profile differed in the two groups.

引用

页码：934 / 947

页数：14

共 31 条

[1] Rate of CRL4CRBN substrate Ikaros and Aiolos degradation underlies differential activity of lenalidomide and pomalidomide in multiple myeloma cells by regulation of c-Myc and IRF4 [J].

Bjorklund, C. C. ;

Lu, L. ;

Kang, J. ;

Hagner, P. R. ;

Havens, C. G. ;

Amatangelo, M. ;

Wang, M. ;

Ren, Y. ;

Couto, S. ;

Breider, M. ;

Ning, Y. ;

Gandhi, A. K. ;

Daniel, T. O. ;

Chopra, R. ;

Klippel, A. ;

Thakurta, A. G. .

BLOOD CANCER JOURNAL, 2015, 5 :e354-e354

[2] Comparison in low-tumor-burden follicular lymphomas between an initial no-treatment policy, prednimustine, or interferon alfa: A randomized study from the Groupe D'Etude des Lymphomes Folliculaires [J].

Brice, P ;

Bastion, Y ;

Lepage, E ;

Brousse, N ;

Haioun, C ;

Moreau, P ;

Straetmans, N ;

Tilly, H ;

Tabah, I ;

SolalCeligny, P .

JOURNAL OF CLINICAL ONCOLOGY, 1997, 15 (03) :1110-1117

[3] Transformed follicular non-Hodgkin lymphoma [J].

Casulo, Carla ;

Burack, W. Richard ;

Friedberg, Jonathan W. .

BLOOD, 2015, 125 (01) :40-47

[4] Report of an international workshop to standardize response criteria for non-Hodgkin's lymphomas [J].

Cheson, BD ;

Horning, SJ ;

Coiffier, B ;

Shipp, MA ;

Fisher, RI ;

Connors, JM ;

Lister, TA ;

Vose, J ;

Grillo-López, A ;

Hagenbeek, A ;

Cabanillas, F ;

Klippensten, D ;

Hiddemann, W ;

Castellino, R ;

Harris, NL ;

Armitage, JO ;

Carter, W ;

Hoppe, R ;

Canellos, GP .

JOURNAL OF CLINICAL ONCOLOGY, 1999, 17 (04) :1244-1253

[5]

Chiu HL, 2017, BLOOD, V130

[6] Hematopoietic growth factors: ESMO Clinical Practice Guidelines for the applications [J].

Crawford, J. ;

Caserta, C. ;

Roila, F. .

ANNALS OF ONCOLOGY, 2010, 21 :v248-v251

[7] Ikaros regulates neutrophil differentiation [J].

Dumortier, A ;

Kirstetter, P ;

Kastner, P ;

Chan, S .

BLOOD, 2003, 101 (06) :2219-2226

[8] Randomized trial of bendamustine-rituximab or R-CHOP/R-CVP in first-line treatment of indolent NHL or MCL: the BRIGHT study [J].

Flinn, Ian W. ;

van der Jagt, Richard ;

Kahl, Brad S. ;

Wood, Peter ;

Hawkins, Tim E. ;

MacDonald, David ;

Hertzberg, Mark ;

Kwan, Yiu-Lam ;

Simpson, David ;

Craig, Michael ;

Kolibaba, Kathryn ;

Issa, Samar ;

Clementi, Regina ;

Hallman, Doreen M. ;

Munteanu, Mihaela ;

Chen, Ling ;

Burke, John M. .

BLOOD, 2014, 123 (19) :2944-2952

[9]

Fowler N., 2015, HEMATOL ONCOL, V33, P200

[10] Safety and activity of lenalidomide and rituximab in untreated indolent lymphoma: an open-label, phase 2 trial [J].

Fowler, Nathan H. ;

Davis, R. Eric ;

Rawal, Seema ;

Nastoupil, Loretta ;

Hagemeister, Fredrick B. ;

McLaughlin, Peter ;

Kwak, Larry W. ;

Romaguera, Jorge E. ;

Fanale, Michelle A. ;

Fayad, Luis E. ;

Westin, Jason R. ;

Shah, Jatin ;

Orlowski, Robert Z. ;

Wang, Michael ;

Turturro, Francesco ;

Oki, Yasuhiro ;

Claret, Linda C. ;

Feng, Lei ;

Baladandayuthapani, Veerabhadran ;

Muzzafar, Tariq ;

Tsai, Kenneth Y. ;

Samaniego, Felipe ;

Neelapu, Sattva S. .

LANCET ONCOLOGY, 2014, 15 (12) :1311-1318

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