Clinical characteristics and survival outcomes of patients with Primary Central Nervous System Lymphoma treated with high-dose methotrexate-based polychemotherapy and consolidation therapies
Menée à partir de données portant sur 346 patients atteints d'un lymphome primitif du système nerveux central, cette étude multicentrique rétrospective évalue l'efficacité, du point de vue de la survie sans progression, de la survie spécifique et de la survie globale, de polychimiothérapies comportant de hautes doses de méthotrexate en traitement d'induction et de consolidation
Given the rarity of primary central nervous system lymphoma (PCNSL), evaluations of different high-dose methotrexate-(HD-MTX)-based treatment regimens is sparse. This retrospective, multicenter study evaluates clinical characteristics and outcomes (progression-free, overall and disease-specific survival) after five HD-MTX-based polychemotherapeutic regimens and two consolidation therapies. 346 patients with histologically confirmed PCNSL, treated with ≥1 cycle HD-MTX-based strategies (≥3g/m2/cycle) were included. The regimens included MATRIX (HD-MTX, HD-AraC, thiotepa, and rituximab), (R)MBVP±HD-AraC (HD-MTX, teniposide/etoposide, carmustine, prednisolone, ±HD-AraC, ±rituximab), (R)MP (HD-MTX, procarbazine, ±rituximab), and a combination of HD-MTX and HD-AraC. The overall response rate after induction was 69%, 28% complete remission and progressive disease was observed in 100 (29%) patients. 126 (36%) patients received consolidation, including high-dose-BCNU-thiotepa with autologous stem cell transplantation (HD-BCNU-TT/ASCT, n=59 (17%)) or whole brain radiotherapy (WBRT, n=67 (19%)).Clinical characteristics associated with adverse mortality risk by multivariable prognostication contained age >60 years (HR 1.61, p=0.011), elevated LDH (HR 1.75, p=0.004) and WHO status ≥2 (HR 1.56, p=0.010). Independently, induction regimens containing HD-AraC demonstrated survival benefit compared to induction regimens without HD-AraC (HR 0.59, p=0.002). Without preference for HD-BCNU-TT/ASCT or WBRT, a favorable effect of consolidation (HR 0.44 and HR 0.42, p<0.001) was confirmed, also with consolidation as time-dependent variable. Competing risk analysis showed similar low incidence of lymphoma-unrelated deaths in consolidated and unconsolidated patients.This study confirms that age, elevated LDH and WHO status increase the mortality risk. HD-AraC containing treatment regimens and consolidation with HD-BCU-TT/ASCT or WBRT were associated with superior survival, including a favorable low incidence of lymphoma-unrelated deaths.