Median Absolute Lymphocyte Count Independently Predicts Survival of Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-Chemotherapy: Analysis of 651 Patients Included In the Czech Lymphoma Project
Authors: Prochazka Vit , Trneny Marek , Salek David , Belada David , Kozak Tomas , Papajik Tomas , Pytlik Robert , Vasova Ingrid , Sykorova Alice , Jankovska Milada , Kubackova Katerina , Brejcha Martin , Matuska Milan , Petrakova Katarina , Pirnos Jan , Nepomucka J. , Starostka David , Lysy Milan , Campr Vit , Boudova Ludmila , Trnkova Marie , Petrova Marketa ,   on Behalf Of Czech Lymphoma Study Group
Published: October 2019

Abstract
Abstract 2882
Absolute lymphocyte count (ALC) at time of diagnosis has been documented as an independent predictor of survival in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL). The optimal cut-off values of ALC are still a matter of debate. An extensive analysis of the prognostic impact of ALC in the elderly population treated with rituximab has not yet been carried out. Thus, we assessed the prognostic significance of different ALCs in unselected, newly diagnosed elderly patients with DLBCL in the population of the Central European region (the Czech Lymphoma Project registry). We analyzed data of 651 patients with confirmed DLBCL older than 59 years. Those with CNS involvement were excluded. The median age at diagnosis was 69 years (range, 60–97); the Ann Arbor stages were as follows: I (16.5%), II (26.1%), III (15.9%), and IV (41.5%). The IPI scores were: low (L) 19.8%, low-intermediate (LI) 26.6%, intermediate-high (IH) 24.3%, and high (H) 29.3%. We analyzed the prognostic value of lymphopenia with 3 different cut-off values. Values of ALC < 1.0 × 109/L and ALC < 0.84 × 109/L were chosen according to the previously published data, the third value was the median ALC at diagnosis (ALC 1.35 × 109/L). ALC < 1.0 × 109/L was observed in 201 (31%) and ALC < 0.84 × 109/L in 159 (24%) patients. ALCs below predefined levels were associated with higher (IH, H) IPI scores: ALC < 0.84 × 109/L (78% vs 46%, p < 0.001), ALC < 1.0 × 109/L (77% vs 43%, p < 0.001), and ALC < 1.35 × 109/L (68% vs 38%, p < 0.001); advanced disease (stages III/IV): ALC < 0.84 × 109/L (72% vs 53%, p < 0.001), ALC < 1.0 × 109/L (72% vs 51%, p < 0.001), and ALC < 1.35 × 109/L (66% vs 48%, p < 0.001); and low performance status (ECOG ≥ 2): ALC < 0.84 × 109/L (52% vs 27%, p < 0.001), ALC < 1.0 × 109/L (50% vs 25%, p < 0.001), and ALC < 1.35 × 109/L (43% vs 22%, p < 0.001). In 85% of patients, treatment was initiated with an anthracycline-containing regimen (CHOP), i.e. only 15% of patients recieved a non-anthracycline-based regimen (COP). The median number of chemotherapy cycles was 6. Chemotherapy was combined with rituximab in all patients (a median of 6 doses). Generally, treatment response was assessed in 544 (83.6%) patients. Complete remission (CR) or unconfirmed CR was achieved in 79.8% and partial remission in 12.5% of patients, with 7.7% of patients being classified as having stable disease or disease progression. CR rates were significantly higher in patients with higher lymphocyte counts: ALC > 0.84 × 109/L (82% vs 71%, p = 0.006), ALC >1.0 × 109/L (83.1% vs 71.7%, p = 0.008), and ALC > 1.35 × 109/L (85% vs 75%, p = 0.027). The overall survival (OS) and event-free survival (EFS) rates were superior in all subgroups of patients with higher ALC levels. The 3-year OS rates stratified by lymphocyte count: ALC > 0.84 × 109/L (67% vs 51%, p = 0.0002), ALC > 1.0 × 109/L (67% vs 52%, p = 0.0017), and ALC > 1.35 × 109/L (71% vs 55%, p = 0.0001). The 3-year EFS rates stratified by lymphocyte count: ALC > 0.84 × 109/L (61% vs 44%, p = 0.0002), ALC > 1.0 × 109/L (62% vs 44%, p = 0.0002), and ALC > 1.35 × 109/L (66% vs 47%, p < 0.0001). Only ALC < 1.35 × 109/L was found to be an independent negative prognostic factor for the OS (RR = 1.53, p = 0.006) and EFS (RR = 1.43, p = 0.013) in a multivariate analysis when compared with the LDH level, clinical stage, performance status and age (above median). In summary, the data support the hypothesis that host innate immunity is critical in tumor growth control and is a limiting factor for the efficacy of immunochemotherapy in elderly patients with DLBCL. The optimal cut-off levels of ALC may be different in various populations. This fact should be taken into account when designing new ALC-based prognostic schemes.

Disclosures:
Prochazka: ROCHE: Honoraria. Pytlik:ROCHE: Honoraria.