Clinical Features, Therapy Patterns and Survival Outcomes of Limited-Stage Peripheral T-Cell Lymphomas: A Cross-Continental Study

Introduction: Peripheral T-cell lymphomas (PTCL) encompass a diverse group of mature T-cell neoplasms characterized by unfavorable prognosis, with limited-stage (LS) disease presentation being particularly rare. Current clinical practice in LS PTCL varies, with some clinicians employing abbreviated courses of chemotherapy in conjunction with radiotherapy (RT) (combined modality therapy, CMT), while others adopt more aggressive approaches. This variability is due to the high relapse rates observed in PTCL and the lack of supporting evidence from clinical trials. Most evidence for management arises from real-world studies encompassing all stages of PTCL, with the limited available studies involving small cohorts, leaving the optimal management of LS PTCL undefined. To reduce this knowledge gap, we describe the presentation and management of LS PTCL, and compared outcomes across therapy approaches. Methods: We conducted a retrospective international pooled cohort study of patients (pts) aged ≥18 with newly diagnosed LS PTCL during 2000-2023. Data were obtained from the Grupo de Estudio Latinoamericano de Linfoproliferativos (GELL) registry, the Brazilian T Cell Project (BTCP), and two academic US cancer centers. Primary and secondary endpoints were overall survival (OS) and progression-free survival (PFS). We stratified PTCL subtypes as anaplastic large cell lymphoma (ALCL, regardless of ALK status) and non-ALCL groups (i.e., PTCL not otherwise specified [NOS]; angioimmunoblastic T cell lymphoma [AITL]; and lymphomatous type adult T cell leukemia/lymphoma [L-ATL]). Chemotherapy regimens were classified as brentuximab vedotin (BV)-based (i.e., BV-CH[E]P); CHOP and intensive chemotherapy [iCT] (e.g., CHOEP, EPOCH, HyperCVAD) with or without RT. A pre-pooled analysis confirmed no heterogeneity in endpoints based on regions (i.e., US vs Latin America), suggesting the feasibility of combining the data. Outcomes of first-line therapy are presented by PTCL stratification. Time-to-event endpoints were analyzed using Kaplan-Meier. Results: We enrolled 333 pts (GELL 44%, BTCP 30%, US 26%). The overall median age at diagnosis was 56 years (18-95); most were male (60%), had stage II disease (62%), nodal presentation (65%), ECOG 0-1 (86%), lacked B symptoms (65%), normal serum LDH (54%) and serum albumin >3.5 g/dL (81%). PTCL NOS was the most common non-ALCL subtype (53% vs 8% AITL and 8% L-ATL); 31% were ALCL (ALK+ 15%, ALK- 14%, unknown 2%). Most pts (91%) received first-line therapy with curative intent. CHOP (40%) and iCT (40%) were the most common approaches; only 12% received BV-based therapy and were generally treated at US centers. CMT was given to 27% of LS PTCL. With a median follow-up of 36.2 months in all pts, the 3-year OS and PFS rates were 67% and 52%, respectively. Better survival was seen in ALCL than non-ALCL pts (OS 87% [95% CI 79-94] vs 56% [48-65]; PFS 70% [61-81] vs 42% [35-51], both p<0.001, respectively). The overall response and complete response (CR) rates of BV-, CHOP- and iCT-based approaches were 91% (CR 77%), 81% (CR 62%) and 80% (CR 57%), respectively. None of the chemotherapy regimens offered OS or PFS advantage for ALCL and non-ALCL subtypes. However, in ALCL pts, CMT conferred superior OS (100% [100-100] vs 80% [71-92], p=0.025) and PFS (100% [100-100] vs 57% [45-73], p<0.001) than chemotherapy alone. This effect remains positive even in those managed with abbreviated courses (e.g. 3-4 chemo cycles followed by RT). A non-statistically significant trend towards improved OS (p=0.072) and PFS (p=0.10) was seen in non-ALCL pts treated with CMT; yet, pts aged >70 had better OS (83% [58-100] vs 31% [14-67] p=0.027) and PFS (42% [15-100] vs 21% [8-55] p=0.025) with CMT. Conclusion: In this large study evaluating LS PTCL, most pts were middle-aged, fit, and presenting with nodal disease. Our findings suggest no survival benefit of BV-based over other chemotherapy approaches in LS PTCL, contrasting previous studies that included all PTCL stages. However, RT consolidation provided a survival advantage in ALCL and elderly non-ALCL pts. This research provides critical insights into the management and outcomes of this rare subset of aggressive lymphomas, contributing to optimizing therapeutic strategies in LS PTCL. Future prospective studies should validate our findings. Additional data, including response rates in specific PTCL subtypes, will be presented at the meeting.