Impact of Anthracycline Dose in Elderly Patients with Difusse Large B Cell Lymphoma (DLBCL) at the Instituto Nacional De Cancerologia Mexico
Authors: Nolasco -Medina Diana , Alejandro Mohar , Reynoso-Noveron Nancy , Aviles-Salas Alejandro , Garcia Osvaldo , Candelaria Myrna 
Published: October 2019

Abstract
Background: Lymphoproliferative disorders have increased in last decades. The value of the cyclophosphamide, adriamycin, vincristine and prednisone (CHOP) plus rituximab (R-CHOP) combination therapy in both aggressive and indolent B-cell lymphoma has been demonstrated in several clinical trials. Treatment of patients > 65 years remains controversial and chemotherapy dose has been decreased due to comorbities, particularly cardiac insuficiency
Methods: Retrospective, comparative, non randomized study. Inclussion criteria: > 65 years patients with hystologically diagnosis of DLBCL, treated in a single national reference, from January 2011 until January 2015. Demographic characteristics, comorbidities were analyzed. Three regimens of treatment (RCHOP , RChOP & RCOP, see doses in table) were compared in terms of response, efficacy and survival. Descriptive analysis was done fore demographic & clinical characteristics. Suvival was calculated with Kaplan-Meier method Log rank test analysis was done to compare DFS & OS, stratifed by treatment regimen.
Results:
141 cases, with a median age of 74.15 y (range 65- 96 y), None difference was found among the 3 treatment regimens for the following variables: Comorbities are detailed by treatment group in the following table. (25 % Diabetes mellitus, 29 % blood hypertension), B symptoms (70 %), clinical stage III- IV ( 68 %), most had an adequate ECOG (1-2: 90 %), and most were considere as high-intermediate or high risk (68 %) according with R-IPI scale. However, only a higher proportion of patients with GC subtype was documented in RCHOP patients (54.7 % vs 35 % and 27.1% in RChOP & RCOP groups, respectively.
Global response (CR + PR) was achieved in 77.3 %, 60 % & 68.8 % in patients treated with RCHOP, RChop & RCOP, respectively. The following table describes toxicities by treatment regimen. DFS (but not OS) and OS was better in patients with RCHOP.
Table. RCHOP RChoP RCOP P Doses 375 mg/m² RTX, 750 mg/m² CFM, 50 mg/m² DOXO, 1.4 mg VCR ,100 mg daily x 5 PDN 375 mg/m² RTX, 750 mg/m² CFM, 25 mg/m² DOXO, 1.4 mg VCR ,100 mg daily x 5 PDN 375 mg/m² RTX, 750 mg/m² CFM, 1.4 mg VCR ,100 mg daily x 5 PDN -- N (%) 53 (100) 48 (100) 40 (100) -- Blood arterial hypertention 26.4 % 27.1 % 35 % 0.62 Diabetes mellitus 11.3 % 25 % 32.5 % 0.042 DiabeteR-IPI (3-4) 58.5 % 60.4 % 65 % 0.85 Complications of treatment: Infections None/ambulatory/hospitalization 18/15/8 14/12/1112 23/10/43 0.090 MyelosupressionNone/none without transfusion required/ required transfusion 36/6/11 30/8/10 26/5/9 0.948 Other complication (G III-IV):None Cardiovascular Renal Gastrointestinal Neuropathy Thrombosis - 28 8 4 8 1 1 - 17 5 7 5 5 3 - 24 4 2 6 2 0 0.359 Disease free survival Median (P25-P75) -33.26 (25.43-39.10) 26.13(19.85-30.33) 36.16 (26.76-37.83) 0.011 Overall survival Media (95 % Confidence interval) 37.7 (32.7-42.7)) 29.44 (23.60-35.28) 27.09 (20.81-33.37) 0.135
Conclussion: The group of patients treated with RChOP & RCOP had a worse DFS and but not OS, which may be influenced by a either higher proportion of patients with non-GC subtype, or reduction of anthracycline dose. Although regimens with chemotherapy dose reductions (mini-RCHOP) have been accepted for these patients, an individual evaluation is recommended in this population.

Disclosures
No relevant conflicts of interest to declare.