title: Intensive chemotherapy and immunotherapy in patients with newly diagnosed primary CNS lymphoma: CALGB 50202 (Alliance 50202).
abstract: OBJECTIVE
  Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome.
  
  
  METHODS
  Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial.
  
  
  RESULTS
  The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age > 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival.
  
  
  CONCLUSIONS
  CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT.
authors.affiliation: Helen Diller Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. jamesr@medicine.ucsf.edu
authors.forename: James L
authors.initials: JL
authors.lastname: Rubenstein
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hsi
authors.forename: Jeffrey L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Sin-Ho
authors.initials: SH
authors.lastname: Jung
authors.forename: Megan O
authors.initials: MO
authors.lastname: Nakashima
authors.forename: Barbara
authors.initials: B
authors.lastname: Grant
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Cheson
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Kaplan
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy* / Q000401:mortality; D002648:Child; D004268:DNA-Binding Proteins / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D051560:Proto-Oncogene Proteins c-bcl-6
chemical_list: C084103:BCL6 protein, human; D004268:DNA-Binding Proteins; D051560:Proto-Oncogene Proteins c-bcl-6