The role of maintenance strategies in lymphoma and CLL
Purchase on Springer.com
$39.95 / €34.95 / £29.95*
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.
Maintenance treatment is used in patients if a curative therapy is not available and is currently explored where curation rates need to be improved in aggressive lymphoma. A discussion of valid endpoints is specifically important in the case of indolent lymphoma. The most valid endpoint for maintenance treatment is clearly overall survival, but adequate trial designs may be difficult to achieve and times to relevant results may be excessive. Therefore other endpoints such as quality-adjusted life year or the time to resistance to maintenance treatment or to resistance to repeated reinduction therapies are explored. Several drugs are used for maintenance treatment. The best data exist for interferon alfa and Rituximab. Interferon alfa is able to prolong survival in indolent lymphoma, but it has too many side effects. Rituximab had proven efficacy in second remission in follicular lymphoma and may be useful even in first remission. It has also proven effective in mantle-cell, marginal, and small lymphocytic lymphoma. Maintenance strategies for chronic lymphocytic leukemia have only been explored in phase II designs so far. However, a number of trials currently explore the use of Rituximab or Lenalidomide in a randomized fashion for chronic lymphocytic leukemia maintenance. At all entities included in the overview, several maintenance treatment trials are under way and patients are to be entered in these trials.
- Cheson BD, Pfistner B, Juweid ME, Gascoyne RD, Specht L, Horning SJ, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007 Feb 10;25(5):579–86. CrossRef
- Miyamoto JM, Eraker SA. Parameter estimates for a QALY utility model. Med Decis Making. 1985 Summer;5(2):191–213. CrossRef
- Horning SJ, Rosenberg SA. The natural history of initially untreated low-grade non-Hodgkin’s lymphomas. N Engl J Med. 1984 Dec 6;311(23):1471–5. CrossRef
- Rohatiner AZS, Gregory WM, Peterson B, Borden E, Solal-Celigny P, Hagenbeek A, et al. Meta-analysis to evaluate the role of interferon in follicular lymphoma. J Clin Oncol. 2005 April 1;23(10):2215–23. CrossRef
- Vidal L, Gafter-Gvili A, Salles G, Dreyling MH, Ghielmini M, Hsu Schmitz S-F, et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: an updated systematic review and meta-analysis of randomized trials. J Natl Cancer Inst. 2011 Dec 7;103(23):1799–806. CrossRef
- Gilles S, John Francis S, Fritz O, Armando L-G, David B, Luc X, et al. Rituximab maintenance for 2 years in patients with high tumor burden follicular lymphoma responding to rituximab plus chemotherapy (PRIMA): a phase 3, randomized controlled trial. Lancet. 2011;377(9759):42–51. CrossRef
- Ardeshna KM, Qian W, Smith P, Warden J, Stevens L, Pocock CF, et al. An intergroup randomized trial of rituximab versus a watch and wait strategy in patients with stage II, III, IV, asymptomatic, non-bulky follicular lymphoma (Grades 1, 2 and 3a). A preliminary analysis. ASH annual meeting abstracts. 2010 Nov 19;116(21):6.
- Williams ME, Hong F, Kahl BS, Gayscoyne RD, Wagner LI, Krauss JC, et al. A subgroup analysis of small lymphocytic and marginal zone lymphomas in the Eastern cooperative Oncology group protocol E4402 (RESORT): a randomized phase III study comparing two different rituximab dosing strategies for low tumor burden indolent non-Hodgkin lymphoma. J Clin Oncol. (abstract). 2012;30(15_suppl):abstract #8007.
- Rummel MJ, Niederle N, Maschmeyer G, Banat A, Gruenhagen Uv, Losem C, et al. Bendamustine plus rituximab is superior in respect of progression free survival and CR rate when compared to CHOP plus rituximab as first-line treatment of patients with advanced follicular, indolent, and mantle cell lymphomas: final results of a randomized phase III study of the stiL (Study group indolent lymphomas, Germany). ASH Annual Meeting Abstracts. 2009 Nov 20;114(22):405.
- Kluin-Nelemans HC, Hoster E, Hermine O, Walewski J, Trneny M, Geisler CH, et al. Treatment of older patients with mantle-cell lymphoma. N Engl J Med. 2012;367(6):520–31. CrossRef
- Avilés A, Cleto S, Huerta-Guzmán J, Neri N. Interferon alfa 2b as maintenance therapy in poor risk diffuse large B-cell lymphoma in complete remission after intensive CHOP–BLEO regimens. Eur J Haematol. 2001;66(2):94–9. CrossRef
- Gisselbrecht C, Schmitz N, Mounier N, Singh Gill D, Linch DC, Trneny M, et al. 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. J Clin Oncol. 2012 December 20;30(36):4462–9. CrossRef
- Hallek M, Fischer K, Fingerle-Rowson G, Fink AM, Busch R, Mayer J, et al. Addition of rituximab to fludarabine and cyclophosphamide in patients with chronic lymphocytic leukemia: a randomized, open-label, phase 3 trial. Lancet. 2010;376(9747):1164–74. CrossRef
- Bosch F, Ferrer A, Lopez-Guillermo A, Gine E, Bellosillo B, Villamor N, et al. Fludarabine, cyclophosphamide and mitoxantrone in the treatment of resistant or relapsed chronic lymphocytic leukemia. Br J Haematol. 2002;119(4):976–84. CrossRef
- Moreton P, Kennedy B, Lucas G, Leach M, Rassam SMB, Haynes A, et al. Eradication of minimal residual disease in B-cell chronic lymphocytic leukemia after alemtuzumab therapy is associated with prolonged survival. J Clin Oncol. 2005;23(13):2971–9. CrossRef
- Bottcher S, Ritgen M, Fischer K, Stilgenbauer S, Busch RM, Fingerle-Rowson G, et al. Minimal residual disease quantification is an independent predictor of progression-free and overall survival in chronic lymphocytic leukemia: a multivariate analysis from the randomized GCLLSG CLL8 trial. J Clin Oncol.30(9):980–8.
- Schweighofer CD, Ritgen M, Eichhorst BF, Busch R, Abenhardt W, Kneba M, et al. Consolidation with alemtuzumab improves progression-free survival in patients with chronic lymphocytic leukemia (CLL) in first remission: long-term follow-up of a randomized phase III trial of the German CLL Study Group (GCLLSG). Br J Haematol. 2009;144(1):95–8. CrossRef
- Lin TS, Donohue KA, Byrd JC, Lucas MS, Hoke EE, Bengtson EM, et al. Consolidation therapy with subcutaneous alemtuzumab after fludarabine and rituximab induction therapy for previously untreated chronic lymphocytic leukemia: final analysis of CALGB 10101. J Clin Oncol. 28(29):4500–6.
- Thieblemont C, Bouafia F, Hornez E, Dumontet C, Tartas S, Antal D, et al. Maintenance therapy with a monthly injection of alemtuzumab prolongs response duration in patients with refractory B-cell chronic lymphocytic leukemia/small lymphocytic lymphoma (B-CLL/SLL). Leuk Lymphoma. 2004;45(4):711–4. CrossRef
- Kaufman MS, Caramanica A, Janson D, Driscoll N, Johnson C, Kohn N, et al. Alemtuzumab maintenance may safely prolong chemotherapy-free intervals in chronic lymphocytic leukemia. Med Oncol. 2011;28(2):532–8. CrossRef
- Mauro FR, Zinzani P, Zaja F, Gentile M, Vegna ML, Stefoni V, et al. Fludarabine plus prednisone ± alpha-interferon followed or not by alpha-interferon maintenance therapy for previously untreated patients with chronic lymphocytic leukemia: long term results of a randomized study. Haematologica. 2003;88(12):1348–57.
- Bosch F, Abrisqueta P, Villamor N, Terol MJ, Gonzalez-Barca E, Gonzalez M, et al. Rituximab maintenance in patients with chronic lymphocytic leukemia (CLL) after upfront treatment with rituximab plus fludarabine, cyclophosphamide, and mitoxantrone (R-FCM): final results of a multicenter phase II trial on behalf of the Spanish CLL study group (GELLC). Blood. 2011;118(21):136–7.
- Egle A, Weiss L, Melchardt T, Gunsilius E, Petzer AL, Fridrik M, et al. Final Analysis of induction treatment with fludarabine, cyclophosphamide plus rituximab (FCR) followed by fludarabine plus rituximab (FR) and remission maintenance therapy with rituximab in previously untreated B-chronic lymphocytic leukemia (B-CLL): the chairos AGMT CLL4/Roche ML18434 Study. Blood. 2010;116(21):593–4.
- Chanan-Khan A, Miller KC, Musial L, Lawrence D, Padmanabhan S, Takeshita K, et al. Clinical efficacy of lenalidomide in patients with relapsed or refractory chronic lymphocytic leukemia: Results of a phase II study. J Clin Oncol. 2006;24(34):5343–9. CrossRef
- Hochster H, Weller E, Gascoyne RD, Habermann TM, Gordon LI, Ryan T, 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 April 1;27(10):1607–14. CrossRef
- Martinelli G, Hsu Schmitz S-F, Utiger U, Cerny T, Hess U, Bassi S, et al. Long-term follow-up of patients with follicular lymphoma receiving single-agent rituximab at two different schedules in trial SAKK 35/98. J Clin Oncol. 2010 Oct 10;28(29):4480–4. CrossRef
- Kahl BS, Hong F, Williams ME, Gascoyne RD, Wagner LI, Krauss JC, et al. Results of eastern cooperative oncology group protocol E4402 (RESORT): a randomized phase III study comparing two different rituximab dosing strategies for low tumor burden follicular lymphoma. ASH annual meeting abstracts. 2011 Nov 18;118(21):LBA-6.
- Forstpointner R, Unterhalt M, Dreyling M, Bock H-P, Repp R, Wandt H, et al. Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG). Blood. 2006 Dec 15;108(13):4003–8. CrossRef
- Hainsworth JD, Litchy S, Shaffer DW, Lackey VL, Grimaldi M, Greco FA. 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 Feb 20;23(6):1088–95. CrossRef
- Pettengell R, Schmitz N, Gisselbrecht C, Caballero D, Colombat P, Conde E, et al. Randomized study of rituximab in patients with relapsed or resistant follicular lymphoma prior to high-dose therapy as in vivo purging and to maintain remission following high-dose therapy. J Clin Oncol. (abstract). 2010;28(15-suppl).
- van Oers MHJ, Van Glabbeke M, Giurgea L, Klasa R, Marcus RE, Wolf M, 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. 2010 June 10;28(17):2853–8. CrossRef
- The role of maintenance strategies in lymphoma and CLL
memo - Magazine of European Medical Oncology
Volume 6, Issue 2 , pp 102-108
- Cover Date
- Print ISSN
- Online ISSN
- Springer Vienna
- Additional Links
- Chronic lymphocytic leukemia
- Maintenance treatment
- Interferon alfa
- Industry Sectors
- Author Affiliations
- 1. 3rd Department of Medicine, Center of Hematology and Medical Oncology, AKh-Linz, Krankenhausstrasse 9, 4010, Linz, Austria
- 2. Department of Internal Medicine III with Hematology, Medical Oncology, Hemostaseology, Infectious Diseases, Rheumatology, Oncologic Center, Laboratory for Immunological and cancer research, Paracelsus Medical University Salzburg, Müllner Hauptstrasse 48, 5020, Salzburg, Austria