HIGH TOXICITY AND POOR SURVIVAL WITH ASSOCIATION CHOP PLUS ETOPOSIDE COMPARED TO CHOP REGIMEN IN 124 BRAZILIAN PATIENTS WITH NODAL PTCL LYMPHOMAS (NPTCL): A REAL-LIFE EXPERIENCE

Abstract

Nodal-PTCL constitute a heterogeneous group of rare malignancies derived from mature T-lymphocytes. It presents aggressive clinical-biological behavior and distinct outcomes. These tumors have significant geographic variation, making important studies of clinical and epidemiological characteristics and outcomes of patients in specific areas of the word. Latin American data on nPTCL are scarce in the literature. Therefore, this study aims to describe clinical, laboratory and epidemiological characteristics, identify prognostic factors and analyze the outcomes of patients with nPTCL treated with CHOP-like regimens in Brazil. This is a retrospective, observational and unicentric study involving 124-Brazilian patients with nPTCL treated at HC–FMUSP from January 2000 to December 2017. All cases were submitted to centralized histopathological review and classified according to the criteria proposed by WHO-2016. OS and PFS curves were estimated by the Kaplan-Meier method. Univariate Cox analysis was used to determine factors with prognostic impact through the association between categorical variables and survival curves. Variables that were significant in the univariate analysis were tested in a multivariate analysis. P-values ≤ 0.05 were considered statistically significant. With a median age of 48.5 years and 57.3% of male, about 81.5% had B-symptoms, 88.7% with CS III/IV and 58.1% had IPI ≥ 3. ORR to first-line treatment was 58.9%, 37.9% were treated with CHOP and 35.5% with CHOEP, 30.1% were submitted to radiotherapy and 32.3% were consolidated with ASCT. We observed a higher 2-year OS for patients treated with CHOP versus CHOEP (78.7% x 61.4%; p = 0.05), as well as a better 2-year PFS for the same regimen (69.7% x 25.0%; p < 0.0001). CHOEP treatment was associated with higher rates of G3-4 neutropenia, febrile neutropenia and G3-4 thrombocytopenia (57% x 88% p = 0.001, 38% x 70% p = 0.003 and 27% x 63% p = 0.0007, respectively). Overall mortality rate was 55.6%, with disease progression being the major cause of death. With a median follow-up of 23.7 months, medians of OS and PFS were 48.0 months (95% CI: 9.0-86.9) and 8.8 months (95% CI: 3.9-13.7), respectively. Estimative of 2-year OS and PFS for the global cohort were 61.3% and 41.5%, respectively. In the univariate analysis, factors with a favorable prognostic impact on OS were: IPI < 3 (HR: 0.30; p < 0.0001), absence of bone marrow infiltration (HR: 0.39; p = 0.005), LDH < 480 U/L (HR: 0.36; p = 0.002), radiotherapy (HR: 0.23; p = 0.001) and ASCT (HR: 0.28; p < 0.0001). Factors associated with better 2-year PFS were: IPI < 3 (HR: 0.36; p = 0.004), absence of bone marrow infiltration (HR: 0.30; p = 0.03), LDH < 480 U/L (HR: 0.36; p = 0.001), radiotherapy (HR: 0.17; p < 0.0001) and ASCT (HR: 0.03; p = 0.001). In the multivariate analysis, factors associated with better 2-year OS were: LDH < 480 U/L (HR: 0.40; p = 0.005) and ASCT (HR: 0.47; p = 0.003). LDH < 480 U/L (HR: 0.45; p = 0.01) and ASCT (HR: 0.07; p = 0.01) were also associated with higher 2-year PFS in our cohort. This is the largest real-life Latin American nPTCL cohort published to date. Patients with nPTCL have poor survival and high rate of chemo-resistance. In our cohort, adding etoposide to the CHOP regimen showed no survival benefit and was associated with high toxicity. Normal values of LDH and consolidation with ASCT were independent factors associated with better outcomes in Brazilian patients with nPTCL.