Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: CALGB 50202 (Alliance 50202)

TLDR

Concerns about neurocognitive toxicity from whole‑brain radiotherapy have driven the development of alternative, dose‑intensive chemotherapeutic consolidation strategies for primary CNS lymphoma. The study aimed to evaluate the complete response rate to induction methotrexate, temozolomide, and rituximab, assess the feasibility of high‑dose etoposide‑plus‑cytarabine consolidation, measure progression‑free survival, and examine clinical and molecular prognostic factors in newly diagnosed primary CNS lymphoma. A multicenter prospective trial enrolled 44 patients who received induction methotrexate, temozolomide, and rituximab, and those achieving complete response underwent high‑dose etoposide‑plus‑cytarabine consolidation, with concurrent molecular biomarker analysis. The regimen achieved a 66 % complete response rate, 2‑year progression‑free survival of 57 %, and demonstrated that high‑dose consolidation was feasible and produced outcomes comparable to WBRT‑based regimens, with treatment delay emerging as the strongest prognostic factor and high BCL6 expression linked to poorer survival.

Abstract

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.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.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.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.