Age-adjusted high-dose chemotherapy followed by autologous stem cell transplantation or conventional chemotherapy with R-MP as first- line treatment in elderly primary CNS lymphoma patients – the randomized phase III PRIMA-CNS trial

Author:

Isbell Lisa K1,Uibeleisen Roswitha2,Friedl Alexander2,Burger Elvira1,Dopatka Tatja1,Scherer Florian1,Orban Andras1,Lauer Eliza1,Malenica Natalie1,Semenova Inna1,Vreden Annika1,Valk Elke3,Wendler Julia2,Neumaier Simone2,Fricker Heidi1,Rabih Abed Al Hadi El1,Gloggengießer Cora3,Hilbig Daniela3,Bleul Sabine1,Weis Joachim1,Gmehlin Dennis2,Backenstrass Matthias2,Wirtz Sebastian1,Ihorst Gabriele1,Finke Jürgen1,Illerhaus Gerald2,Schorb Elisabeth1

Affiliation:

1. Medical Center-University of Freiburg, University of Freiburg

2. Klinikum Stuttgart

3. Stuttgart Cancer Center - Tumorzentrum Eva Mayer-Stihl, Klinikum Stuttgart

Abstract

Abstract Background Older primary central nervous system lymphoma (PCNSL) patients have an inferior prognosis compared to younger patients because available evidence on best treatment is scarce and treatment delivery is challenging due to comorbidities and reduced performance status. High-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) after high-dose methotrexate (HD-MTX)-based immuno-chemotherapy has become an increasingly used treatment approach in eligible elderly PCNSL patients with promising feasibility and efficacy, but has not been compared with conventional chemotherapy approaches. In addition, eligibility for HCT-ASCT in elderly PCNSL is not well defined. Geriatric assessment (GA) may be helpful in selecting patients for the best individual treatment choice, but no standardized GA exists to date. A randomized controlled trial, incorporating a GA and comparing age-adapted HCT-ASCT treatment with conventional chemotherapy is needed. Methods This open-label, multicenter, randomized phase III trial with two parallel arms will recruit 310 patients with newly diagnosed PCNSL > 65 years of age in 40 centers in Germany and Austria. The primary objective is to demonstrate that intensified chemotherapy followed by consolidating HCT-ASCT is superior to conventional chemotherapy with rituximab, HD-MTX, procarbazine (R-MP) followed by maintenance with procarbazine in terms of progression free survival (PFS). Secondary endpoints include overall survival (OS), event free survival (EFS), (neuro-)toxicity and quality of life (QoL). GA will be conducted at specific time points during the course of the study. All patients will be treated with a pre-phase rituximab-HD-MTX cycle followed by re-assessment of transplant eligibility. Patients judged transplant eligible will be randomized (1:1). Patients in arm A will be treated with 3 cycles of R-MP followed by maintenance therapy with procarbazine for 6 months. Patients in arm B will be treated with 2 cycles of MARTA (R-HD-MTX/AraC) followed by busulfan- and thiotepa-based HCT-ASCT. Discussion The best treatment strategy for elderly PCNSL patients remains unknown. Treatments range from palliative to curative but more toxic therapies, and there is no standardized measure to select patients for the right treatment. This randomized controlled trial will create evidence for the best treatment strategy with the focus on developing a standardized GA to help define eligibility for an intensive treatment approach. Trial registration German clinical trials registry DRKS00024085 registered March 29, 2023.

Publisher

Research Square Platform LLC

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