Obinutuzumab-based immunochemotherapy and maintenance therapy resulted in longer progression-free survival than rituximab-based therapy. High-grade adverse events were more common with obinutuzumab-based chemotherapy. (Funded by F. Hoffmann-La Roche; GALLIUM ClinicalTrials.gov number, NCT01332968 .).

The combination of cyclophosphamide, vincristine, and prednisone (CVP) is one of several standard treatment options for advanced follicular lymphoma. This, like similar chemotherapeutic regimens, induces response rates of 60% to 80%, with a median response duration of under 2 years. Rituximab, a chimeric monoclonal antibody against CD20, is active in follicular lymphoma, both as monotherapy and in combination with chemotherapy. Previously untreated patients with stages III to IV follicular lymphoma were randomly assigned to receive either 8 cycles of CVP plus rituximab (R-CVP; n ‫؍‬ 162) or CVP (n ‫؍‬ 159). Overall and complete response rates were 81% and 41% in the R-CVP arm versus 57% and 10% in the CVP arm, respectively (P < .0001). At a median follow-up of 30 months, patients treated with R-CVP had a very significantly prolonged time to progression (median 32 months versus 15 months for CVP; P < .0001). Median time to treatment failure was 27 months in patients receiving R-CVP and 7 months in the CVP arm (P < .0001). Rituximab did not add significantly to the toxicity of CVP.

We evaluated the role of rituximab (R) both in remission induction and maintenance treatment of relapsed/resistant follicular lymphoma (FL). A total of 465 patients were randomized to induction with 6 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) (every 3 weeks) or R-CHOP (R: 375 mg/m 2 intravenously, day 1). Those in complete remission (CR) or partial remission (PR) were randomized to maintenance with R (375 mg/m 2 intravenously once every 3 months for a maximum of 2 years) or observation. R-CHOP induction yielded an increased overall response rate (CHOP, 72.3%; R-CHOP, 85.1%; P < .001) and CR rate (CHOP, 15.6%; R-CHOP, 29.5%; P < .001). Median progressionfree survival (PFS) from first randomization was 20.2 months after CHOP versus 33.1 months after R-CHOP (hazard ratio [HR], 0.65; P < .001). Rituximab maintenance yielded a median PFS from second randomization of 51.5 months versus 14.9 months with observation (HR, 0.40; P < .001). Improved PFS was found both after induction with CHOP (HR, 0.30; P < .001) and R-CHOP (HR, 0.54; P ‫؍‬ .004). R maintenance also improved overall survival from second randomization: 85% at 3 years versus 77% with observation (HR, 0.52; P ‫؍‬ .011). This is the first trial showing that in relapsed/ resistant FL rituximab maintenance considerably improves PFS not only after CHOP but also after R-CHOP induction. IntroductionFor patients with follicular lymphoma (FL) chemotherapy alone has not resulted in improved overall survival (OS) over the past 30 years. [1][2][3][4] Although in most patients complete remissions (CRs) or partial remissions (PRs) can be obtained with either single agents or combination chemotherapy, the clinical course is characterized by a high relapse rate. After relapse, both the response rate and relapse-free survival after subsequent salvage treatment regimens steadily decrease, resulting in a median survival of only 4 to 5 years after first relapse. [5][6][7][8] Therefore, new treatment modalities resulting in increased progression-free survival (PFS) and OS are urgently required. Optimal treatment of patients relapsed after 1 or 2 chemotherapy regimens is largely unknown.Rituximab (R) is a chimeric murine/human anti-CD20 monoclonal antibody capable of killing CD20 ϩ lymphoma cells. Effector mechanisms include complement-mediated cytotoxicity, antibodydependent cellular cytotoxicity, and possibly direct induction of apoptosis. 9,10 In the nonrandomized pivotal study in 166 relapsed low-grade lymphoma patients, monotherapy with rituximab resulted in a response rate of 48%, with a 6% complete remission (CR) rate and a median time to progression in responding patients of 13 months. 11 Toxicity was generally mild to moderate (grade 1 or 2) and occurred primarily with the first infusion. 11 In a subsequent small phase 2 study, the combination of R with cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was shown to be safe and effective. 12 Treatment results in FL might not only be improved by more effective induction...

Analysis of all outcome measures, including OS, confirm the benefit of adding R to CVP in the front-line treatment of FL.