Frontline treatment of follicular lymphoma with fludarabine, cyclophosphamide, and rituximab followed by rituximab maintenance: toxicities overcome its high antilymphoma effect. Results from a Spanish Cooperative Trial (LNHF-03)

References

• A clinical evaluation of the International Lymphoma Study Group classification of non-Hodgkin's lymphoma. The Non-Hodgkin's Lymphoma Classification Project. Blood 1997;89:3909–3918.
   PubMed Web of Science ®Google Scholar
• Cartwright R, Brincker H, Carli PM, et al. The rise in incidence of lymphomas in Europe 1985–1992. Eur J Cancer 1999;35:627–633.
   PubMed Web of Science ®Google Scholar
• Advani R, Rosenberg SA, Horning SJ. Stage I and II follicular non-Hodgkin's lymphoma: long-term follow-up of no initial therapy. J Clin Oncol 2004;22:1454–1459.
   PubMed Web of Science ®Google Scholar
• Ardeshna KM, Smith P, Norton A, et al. Long-term effect of a watch and wait policy versus immediate systemic treatment for asymptomatic advanced-stage non-Hodgkin lymphoma: a randomised controlled trial. Lancet 2003;362:516–522.
   PubMed Web of Science ®Google Scholar
• Liu Q, Fayad L, Cabanillas F, et al. Improvement of overall and failure-free survival in stage IV follicular lymphoma: 25 years of treatment experience at The University of Texas M.D. Anderson Cancer Center. J Clin Oncol 2006;24:1582–1589.
   PubMed Web of Science ®Google Scholar
• Fisher RI, LeBlanc M, Press OW, et al. New treatment options have changed the survival of patients with follicular lymphoma. J Clin Oncol 2005;23:8447–8452.
   PubMed Web of Science ®Google Scholar
• Swenson WT, Wooldridge JE, Lynch CF, Forman-Hoffman VL, Chrischilles E, Link BK. Improved survival of follicular lymphoma patients in the United States. J Clin Oncol 2005;23:5019–5026.
   PubMed Web of Science ®Google Scholar
• Marcus R, Imrie K, Solal-Celigny P, et al. Phase III study of R-CVP compared with cyclophosphamide, vincristine, and prednisone alone in patients with previously untreated advanced follicular lymphoma. J Clin Oncol 2008;26:4579–4586.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Salles G, Mounier N, de Guibert S, et al. Rituximab combined with chemotherapy and interferon in follicular lymphoma patients: results of the GELA-GOELAMS FL2000 study. Blood 2008;112:4824–4831.
   PubMed Web of Science ®Google Scholar
• Friedberg JW. Potential long-term toxicities should influence the choice of therapy for indolent non-Hodgkin's lymphoma. Haematologica 2006;91:1453–1455.
   PubMed Web of Science ®Google Scholar
• Santini G, Chisesi T, Nati S, et al. Fludarabine, cyclophosphamide and mitoxantrone for untreated follicular lymphoma: a report from the non-Hodgkin's lymphoma co-operative study group. Leuk Lymphoma 2004;45:1141–1147.
   PubMed Web of Science ®Google Scholar
• Tam CS, Wolf M, Prince HM, et al. Fludarabine, cyclophosphamide, and rituximab for the treatment of patients with chronic lymphocytic leukemia or indolent non-Hodgkin lymphoma. Cancer 2006;106:2412–2420.
   PubMed Web of Science ®Google Scholar
• Zinzani PL, Pulsoni A, Perrotti A, et al. Fludarabine plus mitoxantrone with and without rituximab versus CHOP with and without rituximab as front-line treatment for patients with follicular lymphoma. J Clin Oncol 2004;22:2654–2661.
   PubMed Web of Science ®Google Scholar
• Hagenbeek A, Eghbali H, Monfardini S, et al. Phase III intergroup study of fludarabine phosphate compared with cyclophosphamide, vincristine, and prednisone chemotherapy in newly diagnosed patients with stage III and IV low-grade malignant non-Hodgkin's lymphoma. J Clin Oncol 2006;24:1590–1596.
   PubMed Web of Science ®Google Scholar
• Demidem A, Lam T, Alas S, Hariharan K, Hanna N, Bonavida B. Chimeric anti-CD20 (IDEC-C2B8) monoclonal antibody sensitizes a B cell lymphoma cell line to cell killing by cytotoxic drugs. Cancer Biother Radiopharm 1997;12:177–186.
   PubMed Web of Science ®Google Scholar
• Yamauchi T, Nowak BJ, Keating MJ, Plunkett W. DNA repair initiated in chronic lymphocytic leukemia lymphocytes by 4-hydroperoxycyclophosphamide is inhibited by fludarabine and clofarabine. Clin Cancer Res 2001;7:3580–3589.
   PubMed Web of Science ®Google Scholar
• Friedberg JW, Taylor MD, Cerhan JR, et al. Follicular lymphoma in the United States: first report of the national LymphoCare study. J Clin Oncol 2009;27:1202–1208.
   PubMed Web of Science ®Google Scholar
• Brown JR, Friedberg JW, Feng Y, et al. A phase 2 study of concurrent fludarabine and rituximab for the treatment of marginal zone lymphomas. Br J Haematol 2009;145:741–748.
   PubMed Web of Science ®Google Scholar
• McLaughlin P, Estey E, Glassman A, et al. Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and interferon alpha. Blood 2005;105:4573–4575.
   PubMed Web of Science ®Google Scholar
• Tam CS, Seymour JF, Prince HM, et al. Treatment-related myelodysplasia following fludarabine combination chemotherapy. Haematologica 2006;91:1546–1550.
   PubMed Web of Science ®Google Scholar
• Laszlo D, Galieni P, Raspadori D, et al. Fludarabine containing-regimens may adversely affect peripheral blood stem cell collection in low-grade non Hodgkin lymphoma patients. Leuk Lymphoma 2000;37:157–161.
   PubMed Web of Science ®Google Scholar
• Rummel MJ, Niederle N, Maschmeyer G, 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. Blood 2009;114(Suppl. 1): Abstract 405.
   Google Scholar
• Ghielmini M, Schmitz SF, Cogliatti SB, 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.
   PubMed Web of Science ®Google Scholar
• Vidal L, Gafter-Gvili A, Leibovici L, et al. Rituximab maintenance for the treatment of patients with follicular lymphoma: systematic review and meta-analysis of randomized trials. J Natl Cancer Inst 2009;101:248–255.
   PubMed Web of Science ®Google Scholar
• Estalilla OC, Medeiros LJ, Manning JT Jr, Luthra R. 5′–>3′ exonuclease-based real-time PCR assays for detecting the t(14;18)(q32;21): a survey of 162 malignant lymphomas and reactive specimens. Mod Pathol 2000;13:661–666.
   PubMed Web of Science ®Google Scholar
• van Dongen JJ, Langerak AW, Bruggemann M, et al. Design and standardization of PCR primers and protocols for detection of clonal immunoglobulin and T-cell receptor gene recombinations in suspect lymphoproliferations: report of the BIOMED-2 Concerted Action BMH4-CT98-3936. Leukemia 2003;17:2257–2317.
   PubMed Web of Science ®Google Scholar
• Sacchi S, Pozzi S, Marcheselli R, et al. Rituximab in combination with fludarabine and cyclophosphamide in the treatment of patients with recurrent follicular lymphoma. Cancer 2007;110:121–128.
   PubMed Web of Science ®Google Scholar
• 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.
   PubMed Web of Science ®Google Scholar
• Forstpointner R, Unterhalt M, Dreyling M, 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;108:4003–4008.
   PubMed Web of Science ®Google Scholar
• Lai GG, Lim ST, Tao M, Chan A, Li H, Quek R. Late-onset neutropenia following RCHOP chemotherapy in diffuse large B-cell lymphoma. Am J Hematol 2009;84:414–417.
   PubMed Web of Science ®Google Scholar
• Ram R, Ben-Bassat I, Shpilberg O, Polliack A, Raanani P. The late adverse events of rituximab therapy–rare but there! Leuk Lymphoma 2009;50:1083–1095.
   PubMed Web of Science ®Google Scholar
• Hirayama Y, Kohda K, Konuma Y, et al. Late onset neutropenia and immunoglobulin suppression of the patients with malignant lymphoma following autologous stem cell transplantation with rituximab. Intern Med 2009;48:57–60.
   PubMed Web of Science ®Google Scholar
• Treon SP, Branagan AR, Ioakimidis L, et al. Long-term outcomes to fludarabine and rituximab in Waldenstrom macroglobulinemia. Blood 2009;113:3673–3678.
   PubMed Web of Science ®Google Scholar
• Cabanillas F, Liboy I, Pavia O, Rivera E. High incidence of non-neutropenic infections induced by rituximab plus fludarabine and associated with hypogammaglobulinemia: a frequently unrecognized and easily treatable complication. Ann Oncol 2006;17:1424–1427.
   PubMed Web of Science ®Google Scholar
• Aksoy S, Dizdar O, Hayran M, Harputluoglu H. Infectious complications of rituximab in patients with lymphoma during maintenance therapy: a systematic review and meta-analysis. Leuk Lymphoma 2009;50:357–365.
   PubMed Web of Science ®Google Scholar
• Foon KA, Boyiadzis M, Land SR, et al. Chemoimmunotherapy with low-dose fludarabine and cyclophosphamide and high dose rituximab in previously untreated patients with chronic lymphocytic leukemia. J Clin Oncol 2009;27:498–503.
   PubMed Web of Science ®Google Scholar
• Hochster HS, Weller E, Gascoyne RD, et al. Cyclophosphamide and fludarabine in advanced indolent lymphoma: results from the ECOG/CALGB intergroup E1496 trial. J Clin Oncol 2007;25(18S Suppl.): Abstract 8004.
   Google Scholar
• Gamberale R, Galmarini CM, Fernandez-Calotti P, et al. In vitro susceptibility of CD4+ and CD8+ T cell subsets to fludarabine. Biochem Pharmacol 2003;66:2185–2191.
   PubMed Web of Science ®Google Scholar
• Rambaldi A, Carlotti E, Oldani E, et al. Quantitative PCR of bone marrow BCL2/IgH+ cells at diagnosis predicts treatment response and long-term outcome in follicular non-Hodgkin lymphoma. Blood 2005;105:3428–3433.
   PubMed Web of Science ®Google Scholar