ESMO 2016 Selected Oral Presentations: DLBCL – HD-MTX is a highly effective prophylaxis in patients with high-risk of CNS relapse

Dr Teresa Calimeri from the San Raffaele Scientific Institute in Milan, Italy, and colleagues presented during the ESMO congress in October 2016 in Copenhagen, Denmark data from a retrospective study of 242 patients with Diffuse Large B-Cell Lymphoma (DLBCL), analyzing the effect of risk-tailored CNS prophylaxis with High-Dose Methotrexate (HD-MTX).

Patients were separated into two groups based upon their relative risk of CNS recurrence, with high-risk defined as either the involvement of specific extranodal organs and/or with an IPI score of 4–5. The prophylaxis schedule was methotrexate for 3–4 cycles intravenously with or without intrathecal chemotherapy (IT). Overall, 95 patients were in the high-risk group (39%) and 147 in the low-risk group (61%). Of the 95 patients in the high-risk group, 47 received no prophylaxis, 11 received IT alone and 36 received HD-MTX ± IT.

Patient Characteristics


  Low Risk (n = 147) High Risk (n = 95)
Median age 66 (range 18-89) 66 (range 24-89)
M/F ratio 1.19 1.44
PS<2 138 (94%) 69 (73%)
B symptoms 42 (29%) 37 (39%)
Extranodal >1 5 (3.4%) 42 (44%)
Bulky disease 37 (25%) 17 (18%)
Stage III-IV 69 (47%) 67 (71%)
IPI 0-3/4-5 147/- 54/41
Testis - 21
Kidney/adrenal - 18
Orbit - 6
Breast - 1
Paranasal/nasal - 8
Skull/spine - 5
Radiotherapy 61 (41%) 33 (35%)


They reported that with a median follow-up time of 51 months, no one in the high-risk with HD-MTX ± IT prophylaxis group developed CNS relapse. However, two patients (18%) in the IT alone prophylaxis group, and 8 patients (17%) in the no prophylaxis group, developed CNS relapse.

Patient Outcomes - Responses After First-Line

  Low Risk (n = 147) High Risk (n = 95)
CR 23 (84%) 70 (74%)
PR 2 (1%) 4 (4%)
SD 1 (0.7%) 0
PD 19 (13%) 19 (20%)
NA* 2 (1.3%) 2 (2%)

*other causes of death: infections and heart failure

Reported three year PFS rates with HD-MTX ± IT were 81%, compared with 46% without HD-MTX. Three year OS rates were reported as 86% (HD-MTX ± IT), compared with 48% (without HD-MTX).

Their main conclusions at the end of this presentation were that combination prophylaxis with HD-MTX ± IT is highly effective in patients with DLBCL with high-risk of CNS relapse. They tempered this result by reminding the audience that this was a retrospective study and that the high mortality rates associated with CNS relapse could result in the reported OS effect.

Following this presentation, a discussion session was chaired by Professor Peter Johnson from the Faculty of Medicine, University of Southampton, UK. Data was presented on the risk of CNS relapse using either the IPI score or the involvement of specific extranodal organs, the two methods by which Calimeri T. et al. defined the high-risk group.

Prof. Peter Johnson then concluded by summarizing that IV MT-HDX is effective as prophylaxis in high-risk groups, the role of IT in this prophylaxis is unclear, however MT-HDX is most likely the best treatment option for patients in this group.

The talk concluded by stating that the evience remains unsatisfactory and is unlikely to improve greatly.

  • Rituximab has reduced the risk of CNS recurrence
  • High dose IV methotrexate is effective in high risk groups
  • It is not clear whether IT prophylaxis contributes usefully
  • In patients with adequate renal function and no other contraindications, high dose IV methotrexate is probably the treatment of choice