High-dose methotrexate-based immuno-chemotherapy for elderly primary CNS lymphoma patients (PRIMAIN study)

Abstract

To investigate immuno-chemotherapy for elderly immuno-competent patients (⩾65 years) with newly diagnosed primary central nervous system lymphoma, we conducted a multicentre single-arm trial. One cycle consisted of rituximab (375 mg/m2, days 1, 15, 29), high-dose methotrexate (3 g/m2 days 2, 16, 30), procarbazine (60 mg/m2 days 2–11) and lomustine (110 mg/m2, day 2)—R-MPL protocol. Owing to infectious complications, we omitted lomustine during the study and consecutive patients were treated with the R-MP protocol. Three cycles were scheduled and repeated on day 43. Subsequently, patients commenced 4 weekly maintenance treatment with procarbazine (100 mg for 5 days). Primary end point was complete remission (CR) after 3 cycles. We included 107 patients (69 treated with R-MPL and 38 with R-MP). In all, 38/107 patients achieved CR (35.5%) and 15 (14.0%) achieved partial remission. R-MP was associated with a lower CR rate (31.6%) compared with R-MPL (37.7%), but respective 2-year progression-free survival (All 37.3% R-MP 34.9% R-MPL 38.8%) and overall survival (All 47.0% R-MP 47.7% R-MPL 46.0%) rates were similar. R-MP was associated with less ⩾grade 3 toxicities compared with R-MPL (71.1% vs 87.0%). R-MP is more feasible while still associated with similar efficacy compared with R-MPL and warrants further improvement in future studies.

Low‐dose lenalidomide maintenance after induction therapy in older patients with primary central nervous system lymphoma

“…PCNSL increasingly appears to be a curable brain tumour. However, in most clinical trials to date, outcomes for patients older than 60 years remain poor, with 1‐year progression‐free survival (PFS) rates of ~40% and median overall survival (OS) in the range of 14–30 months (Zhu et al , ; Omuro et al , ; Fritsch et al , ). Recent data from the Central Brain Tumor Registry and the Surveillance, Epidemiology and End Results Program demonstrated that, while median OS of all PCNSL patients doubled, from 12.5 months in the 1970's to 26 months in the 2010's, progress was restricted to younger patients.…”

Novel agents for primary central nervous system lymphoma: evidence and perspectives

“…Elderly PCNSL patients often cannot tolerate aggressive induction or consolidation chemotherapy; these patients are usually treated with oral chemotherapy after achieving good remission. 56,57 Therefore, such a trial would be interesting for this vulnerable population with great medical need. Clinical evidence for checkpoint inhibition is still limited; however, anti-PD-1 treatment may find its role in the framework of combination treatments, including maintenance, but we speculate that it is very unlikely to be used as a single agent inducing remissions.…”

Primary CNS Lymphoma in the Elderly: The Challenge

“…One retrospective study [3] described the outcome of thiotepa-based chemotherapy with ASCT administered to 52 elderly lymphoma patients, of whom 15 were PCNSL treated by this protocol as first-line approach. Nine of the 14 studies dedicated to elderly patients [7, 12, 25, 26, 28-32] were retrospective, and 4 were phase II studies [4, 5, 9, 27], with one of them designed as a randomized phase II study [4]. Six studies that reported on elderly subgroups were phase II studies [6, 14-16, 34, 35], and 1 was a retrospective analysis of elderly patients in a phase III study [13].…”

“…Fourteen studies were dedicated to elderly patients [4, 5, 7, 9, 12, 24-33], and 7 studies accrued adult patients of all ages but contained information on outcome of the elderly subgroup [6, 13-16, 34, 35]. One retrospective study [3] described the outcome of thiotepa-based chemotherapy with ASCT administered to 52 elderly lymphoma patients, of whom 15 were PCNSL treated by this protocol as first-line approach.…”