CELL OF ORIGIN COMBINED WITH CNS INTERNATIONAL PROGNOSTIC INDEX IMPROVES IDENTIFICATION OF DLBCL PATIENTS WITH HIGH CNS RELAPSE RISK AFTER INITIAL IMMUNOCHEMOTHERAPY

Abstract

Introduction: Central nervous system (CNS) relapse is a rare, and usually fatal, event in diffuse large B‐cell lymphoma (DLBCL). Improved identification of patients (pts) with high CNS relapse risk is needed. The CNS International Prognostic Index (CNS IPI, Schmitz JCO 2016), a clinical prognostic model that identifies pts with higher CNS relapse risk, may be improved by integration of biomarkers. Methods: CNS relapse was analysed in DLBCL pts treated with firstline obinutuzumab (G) or rituximab (R) plus CHOP in the Phase III GOYA study (Vitolo Blood 2016; NCT01287741). Cell‐of‐origin (COO) was assessed using gene expression profiling (Nanostring Lymphoma Subtyping). Cumulative incidence and time to CNS relapse were estimated with Kaplan‐Meier statistics. The impact of variables of interest (CNS IPI score, COO, study stratification factors ‐ number of planned cycles, geographical region) on CNS relapse was assessed using a multivariate (MV) Cox regression model. Results: of 1418 pts, 19.7% were categorised by CNS IPI score as low risk (0‐1) for CNS relapse, 63.0% as intermediate risk (2‐3) and 17.3% as high risk (4‐6). After 29.0 mo (range 0.1‐56.6) median observation, 40 (2.8%) pts developed CNS relapse (21 G‐CHOP; 19 R‐CHOP). Median time to CNS relapse was 8.5 mo (range 0.9‐43.5); 2‐yr CNS relapse rates were 3.0% overall and 0.8%, 2.1% and 9.3%, for the low, intermediate and high risk CNS IPI subgroups, respectively.COO was available in 933 pts (65.8%). In these pts, 2‐yr relapse rates were 1.4%, 2.2% and 10.3% for the low, intermediate and high risk CNS IPI subgroups, respectively (Figure A). Pts with activated B‐cell‐like (ABC) and unclassified subtypes had significantly higher CNS relapse risk vs the germinal‐center B‐cell‐like subtype (2‐yr rates: 6.9%, 4.8% vs 1.5%, respectively). The impact of dual BCL2 and MYC protein expression on CNS relapse risk is being evaluated and will be presented.On MV analysis, CNS IPI score (hazard ratio [HR] 2.06; 95% CI 1.50‐2.82, p < 0.001) and ABC (HR 4.37; 95% CI 1.84‐10.37, p < 0.001) or unclassified COO subtypes (HR 3.94; 95% CI 1.45‐10.68, p = 0.007) were associated with CNS relapse risk. Three risk subgroups were identified according to presence of high CNS IPI score and/or ABC/unclassified COO (n = 933): low risk (L‐R, no risk factors; n = 450, 48.2%); intermediate risk (I‐R, 1 risk factor [high CNS IPI or ABC/unclassified COO]; n = 408, 43.7%); and high risk (H‐R, both risk factors [high CNS IPI and ABC/unclassified COO]; n = 75, 8.0%). Two‐yr CNS relapse risk was 0.5% (L‐R), 4.7% (I‐R) and 15.2% (H‐R) (Figure B). Conclusions: CNS IPI score and ABC/unclassified COO subtypes were independent risk factors for CNS relapse in DLBCL in the GOYA study. Combining these factors improved prediction of CNS relapse vs CNS IPI alone and stratified pts into 3 risk groups, including a small but notable subgroup (8.0%) of pts with a very high risk of CNS relapse (2‐yr risk: 15.2%).