Fotemustine-based therapy in combination with rituximab as a first-line induction chemotherapy followed by WBRT for newly diagnosed primary central nervous system lymphoma: a prospective phase II trial

Objective: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, anddexamethasone (R-FPD) regimen followed by whole-brain radiotherapy (WBRT) for patients with primary central nervous systemlymphoma (PCNSL). Methods: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the FirstAffiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen consisted ofrituximab (375 mg/m2 i.v. on D0), fotemustine (100 mg/m2 i.v. on D1), pemetrexed (600 mg/m2 i.v. on D1), and dexamethasone(40 mg i.v. on D1-5). Patients 60 years or younger who showed a complete response (CR) were treated with 23.4 Gy of WBRT afterthe end of chemotherapy; those older than 60 years with CR were treated with a wait-and-see approach; and those who did not showCR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy + local tumor field irradiation up to 45 Gy, regardless of age. Results: A total of 30 patients were included. After 2 cycles, the objective response rate (ORR) was 96.5% (28/29, 1 CR, 27 PR, 0 SD,and 1 PD). After 4 cycles, the ORR was 73.1% (19/26, 11 CR, 8 PR, 4 SD, and 3 PD). After WBRT, the ORR was 90.9% (10/11, 7 CR,3 PR, and 1 SD). The grade III and IV toxicity responses were mainly leukopenia (20.0%), thrombocytopenia (23.3%), and anemia(10.0%). Conclusions: Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes,providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.