Intensified Rituximab, Methotrexate, Procarbazine, and Cytarabine (R-MPVA) Regimen With Sequential Addition of...

The treatment efficacy, acute toxicity, and neurocognitive sequelae of older patients with primary central nervous system lymphoma (PCNSL) remain therapeutic challenges. The standard first-line therapy consisted of high-dose methotrexate and cytarabine (AraC) and led to a complete response (CR) in half of the patients. To improve the response rate, we proposed intensifying the standard rituximab, methotrexate, procarbazine, vincristine, and cytarabine (R-MPVA) regimen by sequentially adding etoposide (100 mg/m² D2) to R-MPV (R-MPV-E) and ifosfamide (1.5 g/m² Days 1-3) to R-AraC (R-AraC-I) for patients aged between 60 and 70 years. The primary objective of this retrospective study was to determine the CR rates after three and two planned cycles of R-MPV-E and R-AraC-I, respectively. Thirty-two consecutive patients received this regimen between 2013 and 2021 in Lyon University Hospitals. After the R-MPV-E and R-AraC-I sequences, 11 (34.4%) and 26 (81.3%) patients achieved CR or unconfirmed CR (CRu), respectively, with favorable safety profiles (19% and 38%, of ≥ Grade 3 hematological toxicity; 19% and 27%, of ≥ Grade 3 infection during the induction and consolidation, respectively). With a median follow-up of 42.4 months, the 3-year event-free survival (EFS) and overall survival (OS) rates were 40.2% and 63.2%, respectively. Historical comparisons with a subset of patients from the LOC network database revealed an improvement in CR rates of 81% after R-MPV-E/R-AraC-I versus 42.9% and 60.5% after MPVA and R-MPVA, respectively, mainly owing to the addition of ifosfamide to the R-AraC sequence. Similar results were observed in an independent retrospective cohort of 20 patients treated at Toulouse University-Hospital, with a 70% CR rate after R-MPV-E/R-AraC-I. In addition, 7/26 (27%) CR/CRu patients in the main cohort could then be referred for autograft consolidation. In conclusion, this study revealed that ifosfamide combined with R-AraC could increase the CR/CRu rate at the end of induction in 60-70-year-old PCNSL patients.