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Current Oncology Reports
Published in: Current Oncology Reports 6/2010

01-11-2010

Maintenance and Consolidation Strategies in Non-Hodgkin’s Lymphoma: A Review of the Data

Author: Fredrick B. Hagemeister

Published in: Current Oncology Reports | Issue 6/2010

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Abstract

Results of treatment for patients with non-Hodgkin’s lymphomas have significantly improved over the last decade, especially following the discovery that anti-CD20 antibody therapy can significantly change the outlook for patients with both aggressive and indolent lymphomas. Although investigators have previously attempted to prevent relapses by intensifying chemotherapy programs for patients with poor-risk disease, further improvements in treatment will require development of biologic agents that can be added to current programs and exploitation of currently available drugs that can prevent recurrence of these diseases with good tolerability. This review analyzes currently available plans that can be used to maintain responses or “consolidate” initial responses to therapy, programs that may prevent relapse and potentially cure more patients with lymphomas, with a review of current ongoing trials designed along these lines.
Literature
1.
•• McLaughlin P, Grillo-Lopez AJ, Link BK, et al.: Rituximab chimeric anti-CD20 monoclonal antibody therapy for relapsed indolent lymphoma: half of patients respond to a four-dose treatment program. J Clin Oncol 1998, 16:2825–2833. This article describes the pivotal experience with rituximab, the first antibody approved by the FDA for therapy of cancer.
2.
Hagenbeek A, Gadeberg O, Johnson P, et al.: First clinical use of ofatumumab, a novel fully human anti-CD20 monoclonal antibody in relapsed or refractory follicular lymphoma: results of a phase 1/2 trial. Blood 2008, 111:5486–5495.CrossRefPubMed
3.
Morschhauser F, Leonard JP, Fayad L, et al.: Humanized anti-CD20 antibody, veltuzumab, in refractory/recurrent non-Hodgkin's lymphoma: Phase I/II results. J Clin Oncol 2009, 27:3346–3353.CrossRefPubMed
4.
Morschhauser F, Marlton P, Vitolo U, et al.: Interim results of a phase I/II study of ocrelizumab, a new humanized anti-CD20 antibody in patients with relapsed/refractory follicular non-Hodgkin’s lymphoma. Blood (ASH Annual Meeting Abstracts) 2007, 110:abstract 645.
5.
Salles G, Morschhauser F, Cartron P, et al.: A phase I/II study of RO5072759 (GA101) in patients with relapsed/refractory CD20+ malignant disease. Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 234.
6.
Leonard P, Schuster S, Emmanouilides C, et al.: Durable complete responses from therapy with combined epratuzumab and rituximab. Cancer 2008, 113:2714–2723.CrossRefPubMed
7.
Friedberg J, Younes A, Fisher D, et al.: Durable responses in patients treated with galiximab (anti-CD80) in combination with rituximab for relapsed or refractory follicular lymphoma: long-term follow-up of a phase II clinical trial. Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 1004.
8.
Bargou R, Kufer P, Goebeler M, et al.: Sustained response duration seen after treatment with single agent blinatumomab (MT103/MEDI-538) in the ongoing phase I study MT103-104 in patients with relapsed NHL. Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 267.
9.
Hiddemann W, Kneba M, Dreyling M, et al.: Frontline therapy with rituximab added to the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) significantly improves the outcome for patients with advanced stage follicular lymphoma compared with therapy with CHOP alone: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2005, 106:3725–3732.CrossRefPubMed
10.
• Marcus R, Imrie K, Belch A, et al.: CVP chemotherapy plus rituximab compared with CVP as first-line treatment for advanced follicular lymphoma. Blood 2005, 105:1417–1423. This was the first study that demonstrated in a randomized fashion that rituximab plus chemotherapy provided better PFS and OS results than did chemotherapy alone.
11.
Herold M, Haas A, Srock S, et al.: Rituximab added to first-line mitoxantrone, chlorambucil, and prednisolone chemotherapy followed by interferon maintenance prolongs survival in patients with advanced follicular lymphoma: an East German Study Group Hematology and Oncology Study. J Clin Oncol 2007, 25:1986–1992.CrossRefPubMed
12.
Salles G, Mounier N, de Guibert S, et al.: Rituximab combined with chemotherapy and interferon for follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008, 112:4824–4831.CrossRefPubMed
13.
Forstpointner R, Dreyling M, Repp R, et al.: The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group. Blood 2004, 104:3064–3071.CrossRefPubMed
14.
van Oers M, Glabbeke MV, Baila L, et al.: Rituximab maintenance treatment of relapsed/resistant follicular non-Hodgkin’s lymphoma: long-term outcome of the EORTC 20981 phase III randomized intergroup study. J Clin Oncol (ASCO Annual Meeting Abstracts) 2008, 26:abstract 836.
15.
van Oers M: Rituximab maintenance therapy: a step forward in follicular lymphoma. Haematologica 2007, 92:826–832.CrossRefPubMed
16.
Schulz H, Skoetz N, Bohlius J, et al.: Does combined immunochemotherapy with the monoclonal antibody rituximab improve overall survival in the treatment of patients with indolent non-Hodgkin’s lymphoma? Preliminary results of a comprehensive meta-analysis. Blood (ASH Annual Meeting Abstracts) 2005, 106:abstract 351.
17.
• Ghielmini M, Schmitz S, Cogliatti S, et al.: Prolonged treatment with rituximab in patients with follicular lymphoma significantly increases event-free survival and response duration compared with the standard weekly x 4 schedule. Blood 2004, 103:4416–4423. This study provided information suggesting that rituximab maintenance was effective in prolonging remission following single-agent rituximab as induction.
18.
Ghielmini M, Hsu Schmitz S, Martinelli G, et al.: Long-term follow-up of patients with follicular lymphoma (FL) receiving single-agent rituximab at two different schedules in study SAKK 35/98. J Clin Oncol (ASCO Annual Meeting Abstracts) 2009, 27:abstract 8512.
19.
Hochster H, Weller E, Gascoyne R, et al.: Maintenance rituximab after cyclophosphamide, vincristine, and prednisone prolongs progression-free survival in advanced indolent lymphoma: results of the randomized phase III ECOG1496 study. J Clin Oncol 2009, 27:1607–1614.CrossRefPubMed
20.
Hainsworth J, Litchy S, Shaffer D, et al.: Maximizing therapeutic benefit of rituximab: maintenance therapy versus re-treatment at progression in patients with indolent non-Hodgkin’s lymphoma–a randomized phase II trial of the Minnie Pearl Cancer Research Network. J Clin Oncol 2005, 23:1088–1095.CrossRefPubMed
21.
Berinstein N, Grillo-Lopez AJ, White CA, et al.: Association of serum rituximab (IDEC-C2B8) concentration and anti-tumor response in the treatment of recurrent low-grade or follicular non-Hodgkin’s lymphoma. Ann Oncol 1998, 9:995–1001.CrossRefPubMed
22.
Gordan L, Grow W, Pusateri A, et al.: Phase II trial of individualized rituximab dosing for patients with CD20-positive lymphoproliferative disorders. J Clin Oncol 2005, 23:1096–1102.CrossRefPubMed
23.
•• Salles G, Seymour J, Feugier P, et al.: Rituximab maintenance for 2 years in patients with untreated high tumor burden follicular lymphoma after response to immunochemotherapy. J Clin Oncol 2010, 23:abstract 8044. These authors performed the first randomized study of rituximab maintenance following initial therapy for FL using rituximab and chemotherapy, and changed patterns of care.
24.
Hagemeister F: Rituximab for the treatment of non-Hodgkin’s lymphoma and chronic lymphocytic leukaemia. Drugs 2010, 70:2661–2672.CrossRef
25.
Witzig T, Gordon L, Cabanillas F, et al.: Randomized controlled trial of yttrium-90-labeled ibritumomab tiuxetan radioimmunotherapy versus rituximab immunotherapy for patients with relapsed or refractory low-grade, follicular, or transformed B-cell non-Hodgkin’s lymphoma. J Clin Oncol 2002, 20:2453–2463.CrossRefPubMed
26.
Kaminski MS, Zelenetz AD, Press OW, et al.: Pivotal study of iodine I-131 tositumomab for chemotherapy-refractory low-grade or transformed low-grade B-cell non-Hodgkin’s lymphomas. J Clin Oncol 2001, 19:3918–3928.PubMed
27.
Wiseman G, Witzig T: Yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) induces long-term durable responses in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma. Cancer Biother Radiopharmaceuticals 2005, 20:185–188.CrossRef
28.
Witzig T, Flinn I, Gordon L, et al.: Treatment with ibritumomab tiuxetan radioimmunotherapy in patients with rituximab-refractory follicular non-Hodgkin’s lymphoma. J Clin Oncol 2002, 20:3262–3269.CrossRefPubMed
29.
Carella A, Nati S, Orcioni F, et al.: 90Y Ibritumomab tiuxetan as initial treatment for follicular lymphoma (ZEUS Protocol). An Italian Cooperative Study Group. Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 3061.
30.
Kaminski M, Tuck M, Estes J, et al.: 131 I-tositumomab therapy as initial treatment for follicular lymphoma. N Engl J Med 2005, 352:441–449.CrossRefPubMed
31.
Fisher R, Kaminski M, Wahl R, et al.: Tositumomab and iodine-131 tositumomab produces durable complete remissions in a subset of heavily pretreated patients with low-grade and transformed non-Hodgkin’s lymphomas. J Clin Oncol 2005, 23:7565–7573.CrossRefPubMed
32.
Horning SJ, Younes A, Jain V, et al.: Efficacy and safety of tositumomab and iodine-131 tositumomab (Bexxar) in B-cell lymphoma, progressive after rituximab. J Clin Oncol 2005, 23:712–719.CrossRefPubMed
33.
Czuczman M, Witzig T, Gaston B, et al.: Zevalin radioimmunotherapy is not associated with an increased incidence of secondary myelodyplastic syndrome (MDS) or acute myelogenous leukemia (AML). Blood (ASH Annual Meeting Abstracts) 2002, 100:abstract 1386.
34.
Ansell S, Ristow K, Habermann T, et al.: Subsequent chemotherapy regimens are well tolerated after radioimmunotherapy with yttrium-90 ibritumomab tiuxetan for non-Hodgkin’s lymphomas. J Clin Oncol 2002, 20:3885–3890.CrossRefPubMed
35.
Dosik A, Coleman M, Kostakoglu L, et al.: Subsequent therapy can be administered after tositumomab and iodine I-131 tositumomab for non-Hodgkin lymphoma. Cancer 2006, 106:616–622.CrossRefPubMed
36.
Gopal A, Gooley T, Maloney D, et al.: High-dose radioimmunotherapy versus conventional high-dose therapy and autologous hematopoietic stem cell transplantation for relapsed follicular non-Hodgkin lymphoma: A multivariable cohort analysis. Blood 2003, 102:2351–2357.CrossRefPubMed
37.
Shipley D, Greco F, Spigel D, et al.: Rituximab with short duration chemotherapy followed by 90Y ibritumomab tiuxetan as first-line treatment for patients with follicular lymphoma: update of a Minnie Pearl Cancer Research Network phase II trial. J Clin Oncol (ASCO Annual Meeting Abstracts) 2005, 23:abstract 6577.
38.
Jankowitz R, Foon K, Luong T, et al.: Phase II study of short course CHOP-Rituximab followed by 90-Y ibritumomab tiuxetan as first-line treatment for follicular lymphoma: an update and extension of preliminary findings on predictors of relapse. Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 2001.
39.
Leonard J, Coleman M, Kostakoglu L, et al.: Abbreviated chemotherapy with fludarabine followed by tositumomab and iodine I 131 tositumomab for untreated follicular lymphoma. J Clin Oncol 2005, 23:5696–5704.CrossRefPubMed
40.
Link B, Kaminski M, Coleman M, Leonard J: Phase II study of CVP followed by tositumomab and iodine I-131 tositumomab (Bexxar therapeutic regimen) in patients with untreated follicular non-Hodgkin’s lymphoma (NHL). J Clin Oncol (ASCO Annual Meeting Abstracts) 2004, 22:abstract 6520.
41.
McLaughlin P, Neelapu S, Fanale M, et al.: R-FND followed by radioimmunotherapy for high-risk follicular lymphoma. Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 3056.
42.
Gregory S, Kassar M, Fung H, et al.: A prospective study evaluating the safety and efficacy of combination therapy with fludarabine plus mitoxantrone followed by yttrium-90 (90Y) ibritumomab tiuxetan (Zevalin) and maintenance rituximab as front line therapy for patients with intermediate or high risk follicular non-Hodgkin’s lymphoma. Blood (ASH Annual Meeting Abstracts) 2007, 110:abstract 1360.
43.
Miller T, Unger J, Spier C, et al.: Effect of adding ibritumomab tiuxetan (Zevalin) radioimmunotherapy consolidation to three cycles of CHOP plus involved-field radiotherapy for limited-stage aggressive diffuse B-cell lymphoma (SWOG 0313). Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 3598.
44.
Hamlin P, Moskowitz C, Wegner B, et al.: Early safety and efficacy analysis of a phase II study of sequential R-CHOP and yttrium-90 ibritumomab tiuxetan (Zevalin) for elderly high risk patients with untreated DLBCL. Blood (ASH Annual Meeting Abstracts) 2005, 106:abstract 926.
45.
• Press O, Unger J, Braziel R, et al.: Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular non-Hodgkin’s lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9991. J Clin Oncol 2006, 24:4143–4149. This is the precursor study to the randomized SWOG trial testing rituximab plus CHOP versus radioimmunotherapy as consolidation following CHOP.
46.
Morschhauser F, Radford J, Van Hoof A, et al.: Phase III trial of consolidation therapy with Yttrium-90-ibritumomab tiuxetan compared with no additional therapy after first remission in advanced follicular lymphoma. J Clin Oncol 2008, 26:5156–5164.CrossRefPubMed
47.
Levy R, Robertson M, Ganjoo K, et al.: Results of a phase III trial evaluating safety and efficacy of specific immunotherapy, recombinant idiotype (Id) conjugated to KLH (Id-KLH) with GM-CSF, compared to non-specific immunotherapy, KLH with GM-CSF, in patients with follicular non-Hodgkin’s lymphoma (fNHL). Clin Cancer Res (AACR Annual Meeting Abstracts) 2008, 99:abstract LB-204.
48.
Freedman A, Neelapu S, Nichols C, et al.: A placebo-controlled phase III trial of patient-specific immunotherapy with mitumprotimut-T (Id-KLH) and GM-CSF following rituximab in patients with CD20+ follicular lymphoma. Blood 2008, 112:asbtract 236.
49.
• Shuster M, Neelapu S, Gause B, et al.: Idiotype vaccine therapy (BiovaxID) in follicular lymphoma in first complete remission: phase III clinical trial results. J Clin Oncol 2009, 27:abstract 2. These investigators demonstrated that vaccine therapy may prolong remissions in patients following induction with intensive chemotherapy.
50.
Inoges S, Rodriguez-Cavillo M, Zabalegui N, et al.: Clinical benefit associated with idiotypic vaccination in patients with follicular lymphoma. J Natl Cancer Inst 2006, 98:1292–1301.CrossRefPubMed
51.
Robertson M, Kahl B, Vose J, et al.: Phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory diffuse large B-cell lymphoma. J Clin Oncol 2007, 13:1741–1746.CrossRef
52.
53.
Chng W, Lau L, Yusof N, Mow B: Targeted therapy in multiple myeloma. CA Control 2005, 12:91–104.
54.
Drach J, Seidl S, Kaufmann H: Treatment of mantle cell lymphoma: targeting the microenvironment. Expert Rev Cancer 2005, 5:477–485.CrossRef
55.
Wiernik P, Lossos I, Tuscano J, et al.: Lenalidomide monotherapy in relapsed or refractory aggressive non-Hodgkin’s lymphoma. J Clin Oncol 2008, 26:4952–4957.CrossRefPubMed
56.
Czuczman M, Vose J, Zinzani P, et al.: Efficacy and safety of lenalidomide oral monotherapy in patients with relapsed or refractory diffuse large-B-cell lymphoma: results from an international study (NHL-003). J Clin Oncol (ASCO Annual Meeting Abstracts) 2009, 27:abstract 19504.
57.
Witzig TE, Wiernik PH, Moore, T, et al.: Efficacy of oral lenalidomide monotherapy in relapsed or refractory indolent non-Hodgkin’s lymphoma: final results of NHL-001. J Clin Oncol (ASCO Annual Meeting Abstracts) 2009, 27:abstract 15.
58.
DeRook I, Odonnell R, Noble B, et al.: R2: Preliminary results of a phase II study of lenalidomide and rituximab in relapsed/refractory indolent non-Hodgkin’s lymphoma (NHL). Blood (ASH Annual Meeting Abstracts) 2008, 112:abstract 3060.
59.
Fowler N, McLaughlin P, Kwak L, et al.: Lenalidomide and rituximab for untreated indolent non-Hodgkin’s lymphoma. J Clin Oncol (ASCO Annual Meeting Abstracts) 2009, 27:abstract 8548.
60.
Nowakowski G, LaPlant B, Habermann T, et al.: A phase I/II trial of lenalidomide and RCHOP (R2CHOP) in patients with newly diagnosed diffuse large B-cell (DLBCL) and follicular grade 3 Lymphoma. Blood (ASH Annual Meeting Abstracts) 2009, 114:abstract 1669.
61.
Hernandez-Ilizaturri F, Deeb G, Zinzani P, et al.: Response of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) with nongerminal center B-cell phenotype to lenalidomide (L) alone or in combination with rituximab (R). J Clin Oncol 2010, 28:abstract 8038.
62.
Huang S, Bjornsti M, Houghton P: Rapamycins: mechanism of action and cellular resistance. Cancer Biol Ther 2003, 2:222–232.PubMed
63.
Fingar D, Blenis J: Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 2004, 23:3151–3171.CrossRefPubMed
64.
Lam L, Davis E, Peirce J, et al.: Small molecule inhibitors of IkB kinase are selectively toxic for subgroups of diffuse large cell lymphoma defined by gene expression profiling. Clin Cancer Res 2005, 11:28–40.CrossRefPubMed
65.
Wanner K, Hipp S, Oelsner M, et al.: Mammalian target of rapamycin inhibition induces cell cycle arrest in diffuse large B cell lymphoma (DLBCL) cells and sensitizes DLBCL cells to rituximab. Br J Haematol 2006, 134:475–484.CrossRefPubMed
66.
Haritunians T, Mori A, O’Kelly J, et al.: Antiproliferative activity of RAD001 (everolimus) as a single agent and combined with other agents in mantle cell lymphoma. Leukemia 2007, 21:333–339.CrossRefPubMed
67.
Hudes G, Carducci M, Tomczak, et al.: Temsirolimus, interferon alfa, or both for advanced renal cell carcinoma. N Engl J Med 2007, 356:2271–2281.
68.
Motzer R, Escudier B, Oudard S, et al.: Phase III trial of everolimus for metastatic renal cell carcinoma: final results and analysis of prognostic factors. Cancer 2010, In press.
69.
70.
Ansell S, Inwards D, Rowland K, et al.: Low-dose single-agent temsirolimus for relapsed mantle cell lymphoma. A phase 2 trial in the North Central Cancer Treatment Group. Cancer 2008, 113:508–514.
71.
Witzig T, Habermann T, Reeder C, et al.: A phase II trial of the oral mTOR inhibitor everolimus in relapsed non-Hodgkin’s lymphoma (NHL) and Hodgkin’s disease. Hematologica (EHA Annual Meeting Abstracts) 2009, 94:abstract 426.
72.
Metadata
Title
Maintenance and Consolidation Strategies in Non-Hodgkin’s Lymphoma: A Review of the Data
Author
Fredrick B. Hagemeister
Publication date
01-11-2010
Publisher
Current Science Inc.
Published in
Current Oncology Reports / Issue 6/2010
Print ISSN: 1523-3790
Electronic ISSN: 1534-6269
DOI
https://doi.org/10.1007/s11912-010-0128-x

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