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 - a Randomized Phase III Trial
Most patients being diagnosed with primary diffuse large B-cell lymphoma of the central nervous system (PCNSL) are 60 years or older. Elderly patients with PCNSL have a poor prognosis and there is a great medical need to improve outcome for this vulnerable population. In Germany and many international centres, there are currently two widely used strategies to treat elderly PCNSL patients who are eligible for high-dose methotrexate (HD-MTX) treatment, which have not yet been compared head-to-head. The R-MP regimen has been established by the Cooperative PCNSL Study Group as a conventional immunochemotherapy standard treatment for elderly patients with newly diagnosed disease and consists of Rituximab, HD-MTX and Procarbazine followed by maintenance therapy with Procarbazine. In contrast, another recently established protocol also includes HD-MTX-based induction therapy, but followed by consolidating high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT). This is an overall more intensive, but substantially shorter treatment approach, feasible for elderly patients being considered eligible for a more intensive treatment. The PRIMA-CNS trial aims to compare these two treatment approaches with respect to survival, response rates and toxicity.
• Immunocompetent patients with newly-diagnosed primary DLBCL of the central nervous system.
• Age \> 70 years or age 65-70 years if not eligible for more intensive treatment (e.g. OptiMATe trial).
• Histologically or cytologically assessed diagnosis of B-cell lymphoma by local pathologist.
• Diagnostic sample obtained by stereotactic or surgical biopsy, cerebrospinal fluid (CSF) cytology examination or vitrectomy.
• Disease exclusively located in the CNS.
• At least 1 measurable lesion.
• Eastern Cooperative Oncology Group (ECOG)-Performance Status (PS) ≤ 2. ECOG PS \> 2 accepted if due to PCNSL symptoms.
• Patients possibly eligible for HCT-ASCT as judged by the treating physician.
• Written informed consent obtained according to international guidelines and local laws by patient or authorized legal representative in case patient is temporarily legally not competent due to his or her disease.
⁃ Additional randomization criteria:
• Patients eligible for HCT-ASCT defined by the EBL score (at most one of the 3 following conditions may apply: ECOG PS \> 1, Barthel Index of activities of daily living (ADL) \< 20 and Lachs geriatric screening \> 3), improvement of PS after pre-phase treatment or clinical judgement by the treating physician after discussion with the study expert team.
• No evidence of disease progression after pre-phase treatment.