Rituximab Maintenance In Patients with Chronic Lymphocytic Leukemia (CLL) After Upfront Treatment with Rituximab Plus Fludarabine, Cyclophosphamide, and Mitoxantrone (R-FCM): Final Results of a Multicenter Phase II Trial On Behalf of the Spanish CLL Study Group (GELLC)

Abstract 293 The effectiveness of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) followed by rituximab maintenance in the treatment of CLL has been investigated in a phase II clinical trial that includes two treatment parts. First, patients were given induction therapy with R-FCM up to 6 cycles, achieving an overall response (OR) rate of 93% and a CR rate of 82% (46% MRD-negative CR) (Bosch et al. J Clin Oncol 27:4578–4584, 2009). Patients achieving CR or PR with the initial part of the treatment received rituximab maintenance. Here we present the final results of the treatment maintenance part, initiated three months after concluding R-FCM, and consisting of rituximab 375 mg/m2 every three months for two years (up to 8 cycles). Sixty-four patients (median age 60 years, 70% male) receiving > 4 cycles of maintenance therapy were evaluated for response, including bone marrow (BM) examination and MRD assessment by four-color flow cytometry of peripheral blood and BM. Patients in whom rituximab maintenance was prematurely interrupted (≤ 4 cycles) due to toxicity were considered as failures. Median number of cycles of maintenance administered was 8 (range, 1 to 8) and 76% of patients completed the entire planned treatment. Treatment was delayed due to insufficient hematological recovery in 9 cycles (2%) and to non-hematological toxicity in 4 cycles (0.8%). Neutropenia was observed in 31.3% of cycles (grade 3&4 in 8.5%), thrombocytopenia in 4.6%, and anemia in 1.2%. At the end of the maintenance therapy, 45% of patients had low IgA serum levels, 37% low IgG, and 66% low IgM. Sixteen patients experienced grade 3&4 infectious episodes, including 9 pneumonia, 2 febrile neutropenia, 1 appendicitis, 1 myositis, 1 herpes zoster, and 1 cerebral abscess. Two patients died, one due to multifocal leukoencephalopathy and the other due to hemophagocytic syndrome. Infectious episodes grade 3&4 were observed in 19.5% of cycles with neutropenia 3&4, but in only 3% of cycles with neutropenia inferior to grade 3 (p Disclosures: Bosch: Hoffman La Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Off Label Use: Rituximab is currently not approved as maintenance therapy for patients with chronic lymphocytic leukemia.