Abstract
Introduction: Patients (pts) with diffuse large B cell lymphoma (DLBCL) and high International Prognostic Index (IPI) or extra-nodal localization are at a higher risk for relapse with central nervous system (CNS) involvement. The current policy at the Rambam Health Care Campus (Haifa, Israel) is to give DLBCL pts 6 cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) together with 4 doses of intrathecal (IT) methotrexate (MTX), which may be followed by 2 additional cycles of an intermediate dose (3 g/m2) of intravenous MTX (ID-MTX). The present study aimed to compare the outcome of DLBCL pts with risk factors for CNS relapse who did or did not receive prophylaxis with ID-MTX.
Methods: We retrospectively evaluated a cohort of DLBCL pts treated at Rambam between the years 1991 and 2012. Overall survival (OS), progression-free survival (PFS) and CNS involvement at relapse were estimated in 203 of 355 pts [96 females, 107 males; median age 59 (range18-90) years]. The study included all pts with the primary diagnosis of DLBCL and risk factors for CNS relapse, i.e., Waldeyer ring (5%), breast (2%), testicular (3%), orbital (1%) involvement, bone marrow involvement (25%), stage IV disease (63%), LDH > normal (68%), ≥1 extra-nodal site (26%), IPI ≥3 (41%). Ten percent of pts had stage I-IE disease, 15% - stage II-IIE, 12% - stage III, 63% - stage IV, 38% had B symptoms. Pts with CNS involvement at diagnosis were excluded from the study.
Results: One hundred and fifty patients (74%) were treated with R-CHOP. In this group, 40% of pts with IPI=0/1, 29% with IPI=2 and 47% with IPI ≥3 received ID-MTX prophylaxis. Sixty four pts received ID-MTX (32%), 14 pts (7%) received IT MTX only, 125 pts had no prophylaxis (62%). At a median follow-up of 92 months, 5% of pts had CNS relapse with no difference in incidence between the study groups. Pts with IPI≥3 treated with ID-MTX had a reduced overall relapse rate and significantly better PFS and OS (table 1).
Conclusion: The addition of 2 cycles of ID-MTX to the R-CHOP regimen improved both PFS and OS of DLBCL pts with IPI≥3. A randomized controlled study is warranted to provide stronger evidence.
| All patients . | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| . | Pts No. . | PFS % . | P . | *HR . | 95% CI . | P . | OS % . | #HR . | 95% CI . |
| ID-MTX | 65 | 60 | 1 | 88 | 1 | ||||
| IT MTX | 15 | 56 | 0.09 | 1.92 | 0.9-4.1 | 0.008 | 43 | 3.27 | 1.4-7.8 |
| No prophylaxis | 123 | 42 | 0.04 | 1.58 | 1.0-2.49 | 0.002 | 51 | 2.49 | 1.4-4.4 |
| R-CHOP Data | |||||||||
| IPI≥3 no prophylaxis | 35 | 20 | 1 | 26 | 1 | ||||
| IPI≥3 +ID-MTX | 31 | 58 | 0.004 | 0.38 | 0.29-0.85 | 0.001 | 67 | 0.29 | 0.14-0.6 |
| All patients . | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| . | Pts No. . | PFS % . | P . | *HR . | 95% CI . | P . | OS % . | #HR . | 95% CI . |
| ID-MTX | 65 | 60 | 1 | 88 | 1 | ||||
| IT MTX | 15 | 56 | 0.09 | 1.92 | 0.9-4.1 | 0.008 | 43 | 3.27 | 1.4-7.8 |
| No prophylaxis | 123 | 42 | 0.04 | 1.58 | 1.0-2.49 | 0.002 | 51 | 2.49 | 1.4-4.4 |
| R-CHOP Data | |||||||||
| IPI≥3 no prophylaxis | 35 | 20 | 1 | 26 | 1 | ||||
| IPI≥3 +ID-MTX | 31 | 58 | 0.004 | 0.38 | 0.29-0.85 | 0.001 | 67 | 0.29 | 0.14-0.6 |
No.: number; *HR: hazard ratio for progression; #HR for mortality; CI: confidential interval
No relevant conflicts of interest to declare.
Author notes
Asterisk with author names denotes non-ASH members.
