Chemoimmunotherapy with methotrexate, cytarabine, thiotepa, and rituximab (MATRix regimen) in patients with primary CNS lymphoma: results of the first randomisation of the International Extranodal Lymphoma Study Group-32 (IELSG32) phase 2 trial

Abstract

Associazione Italiana del Farmaco, Cancer Research UK, Oncosuisse, and Swiss National Foundation.

The role of whole brain radiation in primary CNS lymphoma

“…The addition of thiotepa to rituximab/HD-MTX/HD-Ara-C further increased response rates in this trial, and there was a trend toward better PFS and OS after a median follow-up of 30 months. 16 Based on a systematic review 5 and our updated MEDLINE search, there is only 1 randomized trial that investigated whether consolidative WBRT (45 Gy) can safely be omitted from HD-MTX without compromising OS (primary end point) in patients with newly diagnosed PCNSL who achieved a CR after induction chemotherapy (Table 1). 6 This non-inferiority trial (N 5 551) had several methodological limitations, including a large number of dropouts or patients lost to follow-up, inconsistencies between perprotocol and intention-to-treat analyses, and an underpowered design.…”

“…The first randomization investigated the optimal induction treatment 16 and in the second randomization, patients with at least stable disease were randomly allocated between HDT-ASCT and WBRT (N 5 118); final results are pending. 16 A similar trial in the Association des Neuro-Oncologues d'Expression Française/Groupe Ouest-Est d'Étude des Leucémies et Autres Maladies du Sang (ANOCEF/GOELAMS) group (recruitment target, N 5 140) randomized patients after R-MBVP induction to either WBRT with 40 Gy or HDT-ASCT, with results also pending. These 2 studies will provide evidence for the comparison of HDT-ASCT vs WBRT for consolidation in newly diagnosed PCNSL.…”

A Rare Case of Primary Central Nervous System Lymphoma in an Adolescent Female Treated with High-Dose Methotrexate and Rituximab-Based Chemoimmunotherapy and Consolidation Whole Brain Radiotherapy

“…Treatment-related clinical neurotoxicity in patients with a sustained CR was more frequent in patients who received WBRT (49%) than in those who did not (26%). In the multicenter randomized phase 2 IELSG-32 trial, 227 newly diagnosed patients with PCNSL were randomized (1: 1: 1) to receive 4 courses of HDMTX and cytarabine (group A) or the same combination along with rituximab (group B) or the same methotrexate-cytarabine-rituximab combination along with thiotepa (group C/MATRix regimen) [14]. Patients with responsive or stable disease after induction chemotherapy were randomly allocated between WBRT and ASCT for consolidation.…”

Management of primary central nervous system lymphoma in children

“…23 Prospective randomized trials in adults have demonstrated an improved response rate and PFS when HD-MTX is combined with other chemotherapeutic agents that cross the blood-brain barrier, such as high-dose cytarabine (HD-Ara-C) and thiotepa. 24,25 In most pediatric series, patients with PCNSL have been treated with different chemotherapy regimens; however, common themes exist among these reports (Table 1). In a series of 12 children with PCNSL diagnosed from 1995 to 2003, 10 were treated with chemotherapy alone with a 5-year EFS of 70%.…”

“…A randomized phase 2 trial showed a superior response of the combination of HD-MTX/Ara-C, thiotepa, and rituximab compared with HD-MTX/Ara-C alone, as well as HD-MTX/Ara-C and rituximab. 24 The use of rituximab in systemic B-NHL has been studied in pediatrics in a randomized phase 3 trial. 28 In this study, patients with mature B-NHL were randomly assigned to receive LMB-based chemotherapy with or without rituximab.…”