Intensified Rituximab Induction Followed By Rituximab Maintenance For Low Grade B Cell Lymphoma: A Multicenter, Phase II Study

Rituximab has markedly improved the clinical outcomes of mature B cell lymphoma, and rituximab maintenance therapy has been shown to be beneficial, especially in low grade B cell lymphoma (LGBCL). Several studies evaluated intensified rituximab administration combined with chemotherapy. But so far, there has not been any trial of rituximab mono-therapy with intensive rituximab induction followed by maintenance. A multicenter, phase II trial was conducted to evaluate the efficacy and safety of rituximab as induction, weekly 8 doses, and maintenance therapy for 2 years for LGBCL.

Patients with measurable LGBCL according to the World Health Organization (WHO) classification (2001) without prior rituximab treatment and staged as II, II, or IV by Ann-Arbor, were eligible. Patients received rituximab (375 mg/m²) weekly for 8 weeks as induction therapy, and then patients who did not have progressive disease at the end of induction received maintenance therapy with 4 weeks of rituximab at six-month intervals (up to 2 years or disease progression). Duration of treatment was 2.5 years in total. The primary endpoint was the best overall response rate (ORR). The secondary endpoints were complete response rate (CRR), 3-year progression free survival (PFS), 3-year overall survival (OS), and safety. Survivals were assessed using the Kaplan-Meier method.

Forty-one patients with a median age of 64 years (41 to 79) were enrolled at 12 institutes belonging to the Clinical Hematology Group of National Hospital Organization (CHG-NHO) of Japan from December 2005 to May 2009. The majority of disease histology was follicular lymphoma in 33 patients. Of 41 patients, 15 were diagnosed as high tumor burden based on GELF criteria, and FLIP risk grouping classified all into 12 low risk, 21 intermediate risk, and 12 high risk cases. Four relapsed cases were included, and they have all received prior systemic chemotherapy without rituximab. Of the 41 patients, 31 (75.6%) completed the planned 2.5 years therapy. The best ORR was 75.6% (31/41, 90% CI: 62.2-86.1%), with 63.4% CR. Three-year PFS at a median follow-up time of 43.0 months (5.3-72) was 79.7% (90% CI, 66.6-88.1%). Three-year OS at a median follow-up time of 49.4 months (5.3-72) was 97.4% (90% CI, 87.1-99.5%). Grade 3 toxicities were neutropenia in 2.5% (1/41), elevated ALT in 2.5% (1/41), and infection in 2.5% (1/41). There was no grade 4 toxicity.

Intensified rituximab induction and maintenance therapy was demonstrated to have high activity, with durable PFS and minimum toxicity in LGBCL patients. Although a further large-scale trial is needed, intensified rituximab induction followed by rituximab maintenance could be a good treatment in rituximab naïve LGBCL.

No relevant conflicts of interest to declare.