Consolidation Therapy for Follicular Lymphoma

Consolidation Therapy for Follicular Lymphoma

Christian Buske


| More
dots

The cohorts were from two randomised controlled trials that ran between 1986 and 1994 (the Groupe d’Etude des Lymphomes Folliculaires [GELF-86] study) and 1994 and 2001 (the Groupe d’Etude des Lymphomes de l’Adulte (GELA) study [GELF-96].12 HDT significantly improved event-free survival from relapse and survival after relapse (SAR). Interestingly, patients in relapse fared best when they received rituximab/chemotherapy plus HDT compared with immuno-chemotherapy or HDT alone. Patients treated with a rituximab containing salvage regimen followed by HDT had five-year SAR of more than 90%.12 These data suggest that HDT after rituximab/ chemotherapy may add additional clinical benefit, a question which will be addressed for intermediate-/high-risk FL-treatment-naïve patients by an international study (Ri-CHOP study) co-ordinated by the German Low-grade Lymphoma Study Group (GLSG): in this trial patients in need of therapy will be randomised to either R-CHOP followed by rituximab maintenance or R-CHOP followed by consolidating HDT and subsequent rituximab maintenance. Radioimmunotherapy (RIT) should also be considered in the consolidation setting in relapsed disease, particularly in antibody-refractory patients and in widespread disease following multiple prior therapies.11

The Follicular Lymphoma International Prognostic Index (FLIPI)13 was developed to predict the prognosis of patients with FL. Based on five easily obtained clinical and laboratory parameters such as age, Ann Arbor stage, number of nodal areas, LDH and haemoglobin levels, the FLIPI discriminates between three major subgroups of patients with FL with regard to overall survival, carrying a low- (none to one risk factors), intermediate- (two risk factors) or high-risk (three to five risk factors) factor.14 A recent analysis evaluated FLIPI’s predictive value in rituximab-treated advanced FL patients and found that FLIPI identified high-risk patients with advanced-stage FL after first-line treatment with rituximab chemotherapy.13 There are ongoing efforts to develop a novel prognostic score validated after rituximab chemotherapy.15

Antibody Therapy in Follicular Lymphoma
Rituximab is a chimaeric immunoglobulin G (IgG) kappa monoclonal antibody that recognises the CD20 antigen expressed on normal B cells and most malignant B-cell lymphomas.15 The addition of rituximab to the armamentarium of agents for the treatment of NHL has greatly improved management of the disease. Since its approval for clinical use in 1997, rituximab (either as part of induction treatment or as maintenance therapy)17–23 has improved response rates and prolonged OS in patients with follicular NHL and DLBCL.21 Ongoing research is being conducted to define the timing (schedule) and administration necessary for optimum treatment of hard-to-cure lymphomas.

However, nearly every third patient in the first-line setting25 and about half of patients at relapse19 do not respond to rituximab single-agent treatment, and virtually all patients suffer from recurrent disease or progress at some time after rituximab treatment, revealing the critical need to improve and enhance the efficacy of monoclonal antibody activity. RIT is a new modality of targeted therapy in which conjugated radioisotopes to anti-CD20 antibodies are delivered to tumour targets.

« first‹ previous1234next ›last »
References:
  1. Muller AM, Ihorst G, Mertelsmann R, Engelhardt M, Epidemiology of non-Hodgkin’s lymphoma (NHL), Ann Hematol, 2005;84:1–12.
  2. Jaffe ES, Harris NL, Stein H, et al., Pathology and genetics of tumours of haematopoietic and lymphoid tissues, Lyon: International Agency for Research on Cancer, 2001.
  3. Alexander DD, Mink PJ, Adami HO, et al., The non-Hodgkin lymphomas: a review of the epidemiologic literature, Int J Cancer, 2007;120(Suppl. 12):1–39.
  4. Percy CL, Smith MA, Linet M, et al., Lymphomas and reticuloendothelial neoplasms. In: Ries LAG, Smith MA, Gurney JG, et al. (eds), Cancer Incidence and Survival among Children and Adolescents: US SEER Program 1975–1995, Bethesda, MD: National Cancer Institute, 1999;99–464: 935–50.
  5. Link MP, Shuster JJ, Donaldson SS, et al., Treatment of children and young adults with early-stage non-Hodgkin lymphoma, N Engl J Med, 1997;337:1259–66.
  6. Gerrard M, Cairo M, Weston C, et al., Results of the FAB international study in children and adolescents (C+A) with localised, resected B cell lymphoma (large cell [LCL], Burkitt [BL] and Burkitt-like [BLL]), Proc Am Soc Clin Oncol, 2003;22: abstract 3197.
  7. The Non-Hodgkin’s Lymphoma Classification Project, A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma, Blood, 1997;89:3909–18.
  8. Morton LM, Wang SS, Devesa SS, et al., Lymphoma incidence patterns by WHO subtype in the US, 1992–2001, Blood, 2006;107(1):265–76.
  9. Nathwani BN, Harris NL, Weisenburger D, et al., Follicular lymphoma. In: Jaffe ES, Harris NL, Stein H, Vardiman JW (eds), World Health Organization classification of tumours. Pathology and genetics of tumours of haematopoietic and lymphoid tissues, Lyon: IARC Press, 2001;162–7.
  10. Bierman PJ, Natural history of follicular grade 3 nonHodgkin’s lymphoma, Curr Opin Oncol, 2007;19(5):433–7.
  11. Dreyling M, ESMO Guidelines Working Group, Newly diagnosed and relapsed follicular lymphoma: ESMO clinical recommendations for diagnosis, treatment and follow-up, Ann Oncol, 2008;19(Suppl. 2):77–8.
  12. Sebban C, Brice P, Delarue R, et al., Impact of Rituximab and/or High-Dose Therapy With Autotransplant at Time of Relapse in Patients With Follicular Lymphoma: A GELA Study, J Clin Oncol, 2008; Epub ahead of print.
  13. Buske C, Hoster E, Dreyling M, et al., The Follicular Lymphoma International Prognostic Index (FLIPI) separates high-risk from intermediate- or low-risk patients with advanced-stage follicular lymphoma treated front-line with rituximab and the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) with respect to treatment outcome, Blood, 2006;108: 1504–8.
  14. Solal-Celigny P, Roy P, Colombat P, et al., Follicular Lymphoma International Prognostic Index, Blood, 2004;104:1258–65.
  15. Federico M, Bellei M, Marcheselli L, et al., F2 Prognostic Index, Presented at the 10th International Conference on Malignant Lymphoma, Lugano, 2008; abstract 058.
  16. Reff ME, Carner K, Chambers KS, et al., Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20, Blood, 1994;83:435–45.
  17. Maloney D, Grillo-Lopez AJ, Link BK, et al., IDEC-C2B8 (rituximab) anti-CD20 monoclonal antibody therapy in patients with relapsed lowgrade non-Hodgkin’s lymphoma, Blood, 1997;90:2188–95.
  18. Maloney DG, Grillo-Lopez AJ, Bodkin DJ, et al., IDEC-C2B8: Results of a phase I multiple-dose trial in patients with relapsed non-Hodgkin’s lymphoma, J Clin Oncol, 1997;15:3266–74.
  19. McLaughlin P, Grillo-López 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(8): 2825–33.
  20. Ghielmini M, Hsu Schmitz SF, Burki K, et al., The effect of rituximab on patients with follicular and mantle-cell lymphoma, Ann Oncol, 2000;11(Suppl. 1):S123–6.
  21. Czuczman MS, Grillo-Lopez AJ, McLaughlin PC, et al., Treatment of patients with low-grade B-cell lymphoma with the combination of chimeric anti-CD20 monoclonal antibody and CHOP chemotherapy, J Clin Oncol, 1999;17: 268–76.
  22. Emmanouilides C, Bosserman L, Grody W, Mobilization of peripheral stem cells in patients with indolent lymphoma using a combination of MINE with rituximab, Blood, 1999;94:351b; abstract 4798.
  23. Coiffier B, Haioun C, Ketterer N, et al., Rituximab for the treatment of relapsing refractory aggressive lymphoma: a multicenter phase II study, Blood, 1998;92:1927–32.
  24. A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin’s lymphoma, The Non-Hodgkin’s Lymphoma Classification Project, Blood, 1997;89:3909–18.
  25. Colombat P, Salles G, Brousse N, Rituximab (anti-CD20 monoclonal antibody) as single first-line therapy for patients with follicular lymphoma with a low tumor burden: clinical and molecular evaluation, Blood, 2001;97:101–6.
  26. 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, Blood, 2005;106:3725–32.
  27. 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: 1417–23.
  28. Herold M, Haas A, Srock S, et al., East German Study Group Hematology and Oncology Study. 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;25:1986–92.
  29. Salles GA, Mounier N, de Guibert S, et al., Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: Final analysis of the GELA-GOELAMS FL2000 study with a five-year follow-up, Blood, 2007;110:243a.
  30. van Oers MH, Klasa R, Marcus RE, et al., 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, 2006;108: 3295–3301.
  31. Forstpointner R, Dreyling M, Repp R, et al., German Low-Grade Lymphoma Study Group, 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;104:3064–71.
  32. Forstpointner R, Unterhalt M, Dreyling M, et al., German Low Grade Lymphoma Study Group (GLSG), 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;108:4003–8.
  33. Hainsworth JD, Litchy S, Shaffer DW, et al., Maximizing therapeutic benefit of rituximab: maintenance therapy versus retreatment 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;23:1088–95.
  34. Hochster HS, Weller E, Gascoyne RD, et al, Maintenance rituximab after CVP results in superior clinical outcome in advanced follicular lymphoma (FL): results of the E1496 phase III trial from the Eastern Cooperative Oncology Group and the Cancer and Leukemia Group B, Blood, 2005;106: 106a.
  35. Cheson BD, Radioimmunotherapy of non-Hodgkin lymphomas, Blood, 2003;101:391–8.
  36. Press OW, Unger JM, Braziel RM, et al., Phase II trial of CHOP chemotherapy followed by tositumomab/iodine I-131 tositumomab for previously untreated follicular nonHodgkin’s lymphoma: five-year follow-up of Southwest Oncology Group Protocol S9911, J Clin Oncol, 2006;24: 4143–9.
  37. Leonard JP, 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.
  38. Shipley DL, Greco FA, Spigel DR, 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, 2005;23(16S): abstract 6577.
  39. Zinzani PL, Tani M, Pulsoni A, et al., Fludarabine and mitoxantrone followed by yttrium-90 ibritumomab tiuxetan in previously untreated patients with follicular non-Hodgkin lymphoma trial: a phase II non-randomised trial (FLUMIZ), Lancet Oncol, 2008;9:352–8.
  40. Hagenbeek A, Bischof-Delaloye A, Radford JA, et al., 90Y-Ibritumomab tiuxetan (Zevalin®) consolidation of first remission in advanced stage follicular non-Hodgkin’s lymphoma: First results of the international randomized phase 3 First-Line Indolent Trial (FIT) in 414 patients, Blood, 2007;110:198a

Copyright® 2004 - 2010 Business Briefings, Ltd. All rights reserved.
Touch Oncology is for informational purposes and should not be considered medical advice, diagnosis or treatement recommendations.