908O - High-dose methotrexate (HD-MTX) as CNS prophylaxis significantly improves outcome in patients with high-risk diffuse large B-cell lymphoma (DLBCL)

Date 09 October 2016
Event ESMO 2016 Congress
Session Haematological malignancies
Topics Anticancer Agents
Biological Therapy
Presenter Teresa Calimeri
Citation Annals of Oncology (2016) 27 (6): 313-327. 10.1093/annonc/mdw375
Authors T. Calimeri1, C. Cecchetti1, A. Vignati1, M. Sassone1, M. Foppoli1, L. Scarfò1, M. Ponzoni2, A. Ferreri1
  • 1Department Of Oncohematology, IRCCS San Raffaele, 20132 - Milano/IT
  • 2Pathology Unit, IRCCS San Raffaele, 20132 - Milano/IT



CNS dissemination is lethal in DLBCL. However, risk predictors and effective prophylaxis remain to be defined. Thus, we analysed the value of a risk-tailored CNS prophylaxis in a mono-institutional retrospective series of 242 pts with DLBCL in the rituximab era.


Consecutive HIV-neg adults with DLBCL treated with first-line R-CHOP or similar ± RT were considered. CNS dissemination risk was based on involvement of specific extranodal organs (testis, kidney/adrenal, spine, skull, paranasal sinuses, orbit, and/or breast) and/or International Prognostic Index (IPI) of 4-5. CNS prophylaxis, consisting of 3-4 cycles of MTX 3 g/m2 ± intrathecal chemotherapy (IT) was indicated in pts with high CNS recurrence risk diagnosed after 2007.


242 pts were analyzed (median age 66, range 18-89). CNS dissemination risk was low in 147 (61%) and high in 95 (39%). Prophylaxis was indicated in 47 high-risk pts: 36 pts received HD-MTX ± IT, 11 pts receive only IT due to MTHFR polymorphisms, comorbidity or old age. Unexpected toxicity and interruptions were not recorded. At a median follow-up of 51 months (12-171), 11 (4.5%) pts experienced CNS relapse: 6 in the parenchyma, the others in the meninges. CNS relapse rate was


HD-MTX-based prophylaxis is highly effective in DLBCL with increased risk of CNS recurrence defined by involvement of certain extranodal organs and/or high IPI score. The relevant OS effect of HD-MTX can be explained by the high mortality associated with CNS relapse; however, an influence on systemic disease control cannot be excluded.

Clinical trial identification

Legal entity responsible for the study

IRCCS San Raffaele Scientific Institute, Milan, Italy


IRCCS San Raffaele Scientific Institute, Milan, Italy


All authors have declared no conflicts of interest.