Final results of a multicentre phase II trial of high-dose methotrexate (HD-MTX), cytarabine, thiotepa, and idarubicin (MATILDE regimen) followed by whole-brain irradiation (WBRT) for primary CNS lymphomas (PCNSL).

1530 Background: A phase II trial was designed to assess MATILDE chemotherapy (CHT) regimen in untreated PCNSL pts. This combination includes drugs active in different phases of the cell cycle, with demonstrated efficacy against aggressive lymphomas and able to cross the blood-brain barrier.,PCNSL pts (HIV-, ≤70 ys, PS<4) received 3 courses of MTX 3.5 g/m d1; idarubicin 13 mg/m d2; cytarabine 1.7 g/mx2 d2; and thiotepa 20 mg/m d3; ev.3 wks, followed by WBRT (30-36 Gy in responders and 40 Gy in the others) plus a 9-Gy boost.,Pt Characteristics: 41 pts (median age 57 ys) were enrolled (5/00-1/04). All pts but one had brain lesions, with ocular and meningeal disease in 3/34 (9%) and 7 (17%) pts, respectively. According to the IELSG score [J Clin Oncol 2003;21(2):266], risk was low in 10 (24%) pts, intermediate in 23 (56%) and high in 8 (20%). Response and survival: At the end of CHT, 18 (44%) pts had CR, 13 (32%) PR (ORR=76%), 6 (15%) PD and 4 died of toxicity. Response rate after WBRT was 83% (n=34), with a CR rate of 56% (n=23). Five of the 7 pts with meningeal disease achieved CR, one had PR; 3 of them relapsed but without meningeal involvement; 3 pts with meningeal disease are alive at 14, 30 and 53 mos. 24 pts experienced failure, with a 3-yr FFS of 41±8%. 16 pts are alive, with a median f-up of 36 mos (13-56), and a 5-yr OS of 37±7%. According to the IELSG score, 3-yr OS was 70±12%, 37±10% and 0% (p=0.0002), respectively for pts with low, intermediate and high risk.,G4 neutropenia, thrombocytopenia and sepsis were reported in 54%, 45% and 14% of the 97 delivered courses. Six pts did not complete CHT due to toxicity (lethal in 4). No pt required MTX dose reduction, while 15 pts needed a dose reduction of ≥1 of the other drugs. Complete data on MiniMental Status Examination were available in 13 survivors (median age 49), neurotoxicity was not observed at a median f-up of 26 mos.,MATILDE regimen is active (ORR=76%). Pts >65 ys or with PS=3 require dose corrections. Meningeal disease can be controlled without intrathecal CHT. Neurotoxicity is rare in young pts. The prognostic value of the IELSG score is confirmed. No significant financial relationships to disclose.