Up-front Therapy With CHOP Plus Etoposide in Brazilian nodal PTCL Patients: Increased Toxicity and No Survival Benefit Compared to CHOP Regimen-Results of a Real-Life Study From a Middle-Income Country

Author(s)

de Padua Covas Lage, Luis Alberto ; Brito, Claudio Vinicius ; Barreto, Guilherme Carneiro ; Culler, Hebert Fabricio ; Reichert, Cadiele Oliana ; Levy, Debora ; Costa, Renata de Oliveira ; Nogueira Zerbini, Maria Claudia ; Rocha, Vanderson ; Pereira, Juliana

• Document type: Journal article
• Source: CLINICAL LYMPHOMA MYELOMA & LEUKEMIA; v. 22, n. 11, p. 13-pg., 2022-11-01.

Abstract

This is the largest cohort of Latin American patients with nPTCL treated under real-life conditions. Here, 124 nPTCL Brazilian patients had high rates of chemo-resistance to anthracycline-based regimens and poor clinical outcomes, particularly those with PTCL, NOS, and AITL. We demonstrated that the addition of etoposide to CHOP not only did not add survival benefits, but also showed greater toxicity. For the first time in nPTCL setting, we showed that eight cycles of CHOP-like regimen was not associated with higher ORR and survival when compared with 6 cycles, but upfront consolidation with ASCT significantly improved the outcomes. Background: Nodal peripheral T-cell lymphoma (nPTCL) constitute a heterogeneous group of neoplasms with aggressive behavior and poor-survival. They are more prevalent in Latin America and Asia, although data from Brazil are scarce. Its primary therapy is still controversial and ineffective. Therefore, we aim to describe clinical-epidemiological characteristics, outcomes, predictors factors for survival and compare the results of patients treated with CHOP and CHOEP regimens. Methods: Retrospective, observational and single-center study involving 124 nPTCL patients from Brazil treated from 2000 to 2019. Results: With a median follow-up of 23.7 months, the estimated 2-year overall survival (OS) and progression-free survival (PFS) were 59.2% and 37.3%, respectively. The median age was 48.5 years and 57.3% (71/124) were male, 81.5% (101/124) had B-symptoms, 88.7% (110/124) had advanced disease (stage III/IV) and 58.1% (72/124) presented International Prognostic Index (IPI) score >= 3, reflecting a real-life cohort. ORR to first-line therapy was 58.9%, 37.9% (N = 47) received CHOP-21 and 35.5% (N = 44) were treated with CHOEP-21; 30.1% (37/124) underwent to consolidation with involved field radiotherapy (IF-RT) and 32.3% (40/124) were consolidated with autologous hematopoietic stem cell transplantation (ASCT). The overall response rate (ORR) was similar for CHOP-21 (76.6%) and CHOEP-21 (65.9%), P = .259. Refractory disease was less frequent in the CHOEP-21 group (4.5% vs. 21.2%, P = .018). However, few patients were able to complete 6-cycles of CHOEP-21 (31.8%) than to CHOP-21 (61.7%), P = .003. Delays >= 2 weeks among the cycles of chemotherapy were more frequent for patients receiving CHOEP-21 (43.1% vs. 10.6%), P = .0004, as well as the toxicities, including G3-4 neutropenia (88% vs. 57%, P = .001), febrile neutropenia (70% vs. 38%, P = .003) and G3-4 thrombocytopenia (63% vs. 27%, P = .0007). The 2-year OS was higher for CHOP (78.7%) than CHOEP group (61.4%), P = .05, as well as 2-year PFS (69.7% vs. 25.0%, P < .0001). In multivariate analysis, high LDH (HR 3.38, P = .007) was associated with decreased OS. CR at first line (HR: 0.09, P < .001) and consolidation with ASCT (HR: 0.08, P = .015) were predictors of increased OS. Conclusion: In the largest cohort of nPTCL from Latin America, patients had poor survival and high rate of chemo-resistance. In our cohort, the addition of etoposide to the CHOP-21 backbone showed no survival benefit and was associated with high-toxicity and frequent treatment interruptions. Normal LDH values, obtaintion of CR and consolidation with ASCT were independent factors associated with better outcomes. (AU)

• FAPESP's process: 12/50495-3 - Analysis of gene expression profile of cell proliferation and inflammatory response and the pattern of methylation of tumor suppressor genes p16INK4A and p15INK4b and its implications in the prognosis of peripheral T-cell lymphomas
• Grantee: Juliana Pereira
• Support Opportunities: Regular Research Grants