Rituximab Maintenance Treatment of Relapsed/Resistant Follicular Non-Hodgkin's Lymphoma: Long-Term Outcome of the EORTC 20981 Phase III Randomized Intergroup Study

Abstract

A B S T R A C T PurposeIn 2006, we published the results of the European Organisation for Research and Treatment of Cancer phase III trial EORTC 20981 on the role of rituximab in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). At that time, the median follow-up for the maintenance phase was 33 months. Now, we report the long-term outcome of maintenance treatment, with a median follow-up of 6 years. Patients and MethodsOverall, 465 patients were randomly assigned to induction with either six cycles of cyclophosphamide, doxorubicin, vincristine, prednisone (CHOP) or rituximab plus CHOP (R-CHOP). Those in complete remission or partial remission after induction (n ϭ 334) were randomly assigned to maintenance treatment with rituximab (375 mg/m 2 intravenously once every 3 months) or observation. ResultsRituximab maintenance significantly improved progression-free survival (PFS) compared with observation (median, 3.7 years v 1.3 years; P Ͻ .001; hazard ratio [HR], 0.55), both after CHOP induction (P Ͻ .001; HR, 0.37) and R-CHOP (P ϭ .003; HR, 0.69). The 5-year overall survival (OS) was 74% in the rituximab maintenance arm, and it was 64% in the observation arm (P ϭ .07). After progression, a rituximab-containing salvage therapy was given to 59% of patients treated with CHOP followed by observation, compared with 26% after R-CHOP followed by rituximab maintenance. Rituximab maintenance was associated with a significant increase in grades 3 to 4 infections: 9.7% v 2.4% (P ϭ .01). ConclusionWith long-term follow-up, we confirm the superior PFS with rituximab maintenance in relapsed/ resistant FL. The improvement of OS did not reach statistical significance, possibly because of the unbalanced use of rituximab in post-protocol salvage treatment.

Fludarabine, cyclophosphamide, and rituximab in patients with advanced, untreated, indolent B‐cell nonfollicular lymphomas

“…Our high percentages of remission resulted in impressive rates of survival, particularly in terms of FFS, PFS, and OS, that are superior to those observed in patients with untreated CLL 28,30 and in patients with indolent lymphoma. 34 To our knowledge, our results are the first reported to date demonstrating the best response rate compared with the previously tested treatment regimens: FC and chlorambucil-epirubicin 11,22 ; we demonstrated a consistent improvement in outcome, and FCR conferred benefits with respect to the 38,39 The dose-dense immunochemotherapy followed by a short maintenance treatment phase seems to offer the best treatment option in this subset of patients with indolent NHL. The administration of rituximab in combination with FC chemotherapy was well tolerated, facilitating compliance with the planned dose intensity.…”

Epitope interactions of monoclonal antibodies targeting CD20 and their relationship to functional properties

“…[6][7][8][9][10] More recently, the use of rituximab in maintenance therapy has been shown to further improve outcomes in patients with follicular lymphoma (FL). [11][12][13][14][15][16] This has established rituximab's position as a standardof-care therapy in the treatment of NHL and CLL. [17][18][19] Other anti-CD20 antibodies have been introduced into use, including ofatumumab (Arzerra ® ; Genmab/GlaxoSmithKline), which is a human antibody approved for refractory CLL, 20,21 and tositumomab (Bexxar ® , GlaxoSmithKline) and ibritumomab tiuxetan (Zevalin ® , Spectrum), which are murine antibodies used clinically as radioimmunoconjugates.…”

A phase 1 study of obinutuzumab induction followed by 2 years of maintenance in patients with relapsed CD20-positive B-cell malignancies

“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] Maintenance therapy with rituximab has been demonstrated to significantly improve responses and progression free-survival in both previously untreated and relapsed follicular lymphoma (FL). [16][17][18] However, indolent lymphomas, such as FL and chronic lymphocytic leukemia (CLL) remain incurable, with patients exhibiting relapses after each treatment, highlighting the need for more effective therapies.…”