ORLANDO Combined immunochemotherapy results in superior remission rates and overall survival in recurrent follicular and mantle cell lymphoma, and providing rituximab(Drug information on rituximab) (Rituxan) maintenance therapy prolongs duration of response, according to new findings presented by Martin Dreyling, MD, PhD, at the American Society of Clinical Oncology 41st Annual Meeting (abstract 6527 and abstract 6528). "Combined immunotherapy resulted in superior remission rates and survival rates," said Dr. Dreyling, of the University of Munich, Germany. "To the best of my knowledge, this is the first study that proves that on a solid base of data."
Follicular lymphoma typically follows an indolent course and treatment is indicated only in symptomatic patients. The disease is chemosensitive at relapse, and rituximab has been shown to be effective as monotherapy. The German Low Grade Lymphoma Study Group (GLSG) investigated whether administering rituximab with a fludarabine-containing regimen improved remission rates.
Researchers enrolled patients with advanced-stage indolent lymphoma who had relapsed after chemotherapy and were experiencing symptoms. This represented the first relapse for more than half of the patients in each arm and was at least the second relapse for 44% of patients in the chemotherapy-only group and 41% in the chemotherapy plus rituximab arm. Sixteen percent in the chemotherapy arm were refractory, as were 20% in the chemotherapy/rituximab cohort. About two-thirds of patients in both groups had bone marrow involvement. About half had follicular lymphoma and 41% mantle cell lymphoma.
The initial 133 patients received FCM as follows: fludarabine 25 mg/m2 on days 1 to 3, cyclophosphamide(Drug information on cyclophosphamide) 200 mg/m2 on days 1 to 3, and mitoxantrone(Drug information on mitoxantrone) 8 mg/m2 on day 1. Patients in the R-FCM arm also received rituximab 375 mg/m2 on day 0 or day 1.
Among the 130 randomized patients, 12% of the FCM patients achieved a complete response, compared with 33% in the FCM plus rituximab group (P = .005). In both cohorts, 46% of patients obtained a partial response. Hematological toxicities were similar, except for slightly increased lymphocytopenia in the chemotherapy/rituximab group. The rate of severe infection was low in both study arms, at less than 2%.
After observing superior remission rates with rituximab, 111 additional patients were enrolled in the chemotherapy plus rituximab arm. They achieved similar response rates, 27% complete and 57% partial response.
For all patients, there was significant improvement in progression-free and overall survival in the chemotherapy/rituximab group, Dr. Dreyling said.
In the subgroup of follicular lymphoma patients, 23% in the FCM-arm achieved a complete response vs 39% in the randomized R-FCM arm and 36% in the group later assigned to R-FCM. Partial responses were 48%, 56%, and 60%, respectively. "Overall response for rituximab-treated patients was in the range of 95%," Dr. Dreyling said. "More important was the significant improvement in overall survival."
Mantle cell lymphoma is more aggressive and difficult to treat. None of the 26 patients in the FCM cohort achieved a complete response, compared with 29% of the 24 patients in the randomized R-FCM arm and 20% in the 45 patients later assigned to R-FCM. Partial responses were seen in 46%, 29%, and 55% of patients, respectively. The significant benefit in overall survival for rituximab was also seen in this group.
"We think in a setting of relapsed disease, definitely based on overall survival, combined immunochemotherapy should represent the standard approach in this kind of disease," Dr. Dreyling said.
The researchers continued the study to measure the effect of administering rituximab as maintenance therapy. The 142 patients who had achieved a partial or complete response were randomized to an observation-only arm or to a treatment arm in which they were given four weekly doses of rituximab at 3 months and 9 months after completion of induction therapy.
"There was a significant improvement of response duration in the patients who received rituximab maintenance (P = .02)," Dr. Dreyling said. For the subgroup of 119 patients who initially received R-FCM, the researchers also noted a significant difference in response duration in favor of immunochemotherapy.
"Rituximab maintenance results in significant prolongation of response duration for follicular and mantle cell lymphoma," Dr. Dreyling commented. "The potential long-term effect of rituximab maintenance may result in an improved overall survival."