1. LONG-TERM Outcome of a Fondazione Italiana Linfomi Study Comparing Short Rituximab Maintenance Vs Observation after Brief First-LINE R-FND Chemoimmunotherapy Followed By Rituximab Consolidation in Elderly Patients with Advanced Follicular Lymphoma (FL)
- Author
-
Annarita Conconi, Annalisa Chiarenza, Giuseppe Rossi, Francesca Dutto, Stefano Volpetti, Benedetta Puccini, Eleonora Russo, Stefan Hohaus, Simone Ferrero, Chiara Bottelli, Chiara Rusconi, Luca Baldini, Umberto Vitolo, Federico De Angelis, Carola Boccomini, Marco Ladetto, Claudia Castellino, Stefano Sacchi, Francesco Merli, and Andrea Evangelista
- Subjects
Oncology ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Immunology ,Population ,Follicular lymphoma ,Cell Biology ,Hematology ,medicine.disease ,Biochemistry ,Chemotherapy regimen ,Fludarabine ,Surgery ,Regimen ,Chemoimmunotherapy ,Internal medicine ,medicine ,Rituximab ,Progression-free survival ,business ,education ,medicine.drug - Abstract
Introduction: we previously reported (Vitolo U, JCO 2013) the results of a randomized study with brief first-line chemoimmunotherapy followed by rituximab maintenance vs observation. With a median follow-up of 42 months, 3-year Progression Free Survival (PFS) and Overall Survival (OS) were 66% and 89%, respectively. The addition of Rituximab maintenance gave a benefit to the patients: 2-year PFS was 81% for rituximab maintenance versus 69% for observation with a HR of 0.63 (95% CI: 0.38-1.05, p=0.079), although not statistically significant. Moreover we also found that achievement of Minimal Residual Disease (MRD) negativity predicted a better PFS: 3-year PFS 72% vs 39%, HR 3.1 (Ladetto M, Blood 2013). Overall these data showed the good efficacy of this brief chemoimmunotherapy regimen in elderly FL patients. Aim of this analysis was to report long-term outcome and long-term toxicities of this regimen. Methods: From January 2004 to December 2007, 242 treatment-naive patients aged 60-75 years with FL Grade I, II and IIIa were enrolled by 33 FIL centres. Patients had to have advanced (high tumor burden stage II or stage III-IV) disease requiring treatment: 4 monthly courses of R-FND (standard doses of Rituximab, Fludarabine, Mitoxantrone, Dexamethasone) every 28 days followed by 4 weekly Rituximab infusions as consolidation. Responders patients [complete remission (CR) + unconfirmed CR + partial remission (PR)] were randomized to brief rituximab maintenance (Arm A), once every 2 months for a total of 4 doses, or observation (Arm B). MRD for the bcl-2/IgH translocation was determined on bone marrow cells in a centralized laboratory belonging to Euro-MRD consortium, using qualitative and quantitative PCR. Results: a total of 234 patients began chemoimmunotherapy: after induction and consolidation treatment overall response rate was 86%, with 69% CR. Of these, 210 completed the planned treatment and 202 responders were randomized. Up to date, median follow-up were 96 months from enrollment and 87 months from randomization; additional follow-up data were available for 127/146 (87%) not relapsed/progressed patients. Five- and 7-year PFS for the whole population were 57% and 51%, respectively; 5- and 7-year OS for the whole population were 85% and 80%, respectively. From enrollment, an advantage in term of PFS and also OS was observed in FLIPI low risk patients: 7-year PFS was 67% for low risk versus 38% for intermediate-high risk patients (p Conclusions: the present long-term results of this trial with a prolonged follow-up of 7 years confirm that a good outcome is achievable in elderly FL patients with a short-term chemoimmunotherapy (R-FND + Rituximab consolidation) with a 7-year PFS of 51% and low toxicity. In addition these results did not show clear evidence in favor of a shortened Rituximab maintenance after R-fludarabine containing chemotherapy. Conversely, the achievement of PCR negativity maintains predictive value for a better outcome. Figure 1. Figure 1. Disclosures Off Label Use: Rituximab maintenance was not licensed in first-line treatment for follicular lymphoma at that time in Italy; Rituximab was provided free by Roche.
- Published
- 2015