Central nervous system relapse in younger patients with diffuse large B-cell lymphoma: a LYSA and GLA/DSHNHL analysis

Abstract

The majority of patients with diffuse large B-cell lymphoma (DLBCL) can be cured with immunochemotherapy comprising rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP). Patients suffering progression or relapse in the central nervous system (CNS) face dismal outcomes. The impact of more aggressive regimens used in front-line therapy has not systematically been investigated in this context. To this end, we analyzed a large cohort of 2203 younger DLBCL patients treated on ten German and French prospective phase II and III trials following first-line therapy with R-CHOP, R-CHOEP (R-CHOP+etoposide), dose-escalated R-CHOEP followed by repetitive stem cell transplantation (R-MegaCHOEP), or rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, prednisone (R-ACVBP) followed by consolidation including multiple drugs crossing the blood-brain-barrier (BBB). DLBCL patients with age-adjusted International Prognostic Index (aaIPI) of 0-1 showed very low cumulative incidence (CI) rates of CNS relapse regardless of first-line therapy and CNS prophylaxis (3-year CI 0% - 1%). Younger high-risk patients with aaIPI of 2-3 had 3-year CI rates of 1.6% and 4% after R-ACVBP plus consolidation or R-(Mega)CHO(E)P, respectively (Hazard Ratio 2.4 (95% confidence interval: 0.8-7.4), p=0.118). Thus, for younger high-risk patients, front-line regimens incorporating agents crossing the BBB may reduce often fatal CNS relapse.

Controversies in central nervous system prophylaxis of high-risk diffuse large B-cell lymphoma

“…The French Lymphoma Study Alliance (LYSA) and the German Lymphoma Alliance (GLA) recently analyzed the risk of CNS relapse in 2203 younger patients (age < 60 years) treated in several prospective phase II and phase III trials with R-CHOP, R-CHOEP (R-CHOP and etoposide), dose-escalated R-CHOEP followed by stem cell transplantation (R-MegaCHOEP) or rituximab, doxorubicin, cyclophosphamide, vindesine, bleomycine, prednisone (R-ACVBP) and consolidation including drugs crossing the BBB. The cumulative incidence of CNS relapse was generally low in the high-risk patients (age-adjusted IPI of 2--3, n = 627), especially in those receiving R-ACVBP and consolidation vs. (Mega)-R-CHO (E)P with a 3-year confidence interval (CI) of 1.6 vs. 4% [hazard ratio 2.4 (95% CI: 0.8–7.4), respectively ( P = 0.118] [39]. Although these data are retrospective, it is of interest and supports intensive approaches incorporating agents that cross the BBB in fit patients.…”