Paper Details

ABSTRACT

Background

Peripheral T-cell lymphomas (PTCL) are rare and heterogeneous non-Hodgkin lymphomas of mature T-cell origin. Despite advances in front-line treatment options, outcomes remain poor in non-ALCL PTCL subtypes. Event-free survival (EFS)-based endpoints have found traction as surrogates for overall survival (OS) and can identify patients who need alternative treatments. We characterized survival outcomes including OS, event-free survival (EFS), and subsequent OS (sOS) after early-event endpoints across nodal PTCL subtypes in the Lymphoma Epidemiology of Outcomes (LEO) prospective cohort.

Methods

Patients with PTCL diagnoses based on central pathologic confirmation from LEO (enrollment from 2015-2020) were analyzed. OS was calculated from date of diagnosis to date of death from any cause or last follow-up. EFS was defined as time from diagnosis to progression, retreatment, or death. EFS6, EFS12, and EFS24 were defined as being alive and event-free 6, 12, or 24 months, respectively, after diagnosis. Failure of EFS6, EFS12, or EFS24 meant experiencing an early event prior to said endpoints. sOS was defined as time from achieving EFS6, EFS12, or EFS24, or time from progression if it occurred within the said endpoints to death or last follow-up. EFS and OS were evaluated using Cox regression models and Kaplan-Meier curves across subtypes of nodal PTCL.

Results

A total of 361 patients with nodal PTCL (149 [41%] PTCL-NOS, 108 [30%] PTCL-TFH, 63 [18%] ALK- ALCL, and 41 [11%] ALK+ ALCL) were included. At diagnosis, median age was 62 (interquartile range [IQR] 50-71), 58% male, performance score ≥2 21%, stage III-IV 72%, and IPI 2-5 65%. Patients with non-ALCL subtypes were older (median 64 [IQR 53-72] vs 55 [IQR 44-65], respectively; P<0.001), had more advanced disease (stage III-IV 82% vs 48%, respectively; P<0.001), and had higher IPI scores (IPI 2-5 72% vs 46%, respectively; P<0.001). Among non-ALCL subtypes, patients with PTCL-TFH were older compared to those with PTCL-NOS (median 65 [IQR 58-74] vs 63 [IQR 49-71], respectively; P=0.043) with more advanced-stage disease (stage III-IV 91% vs 76%, respectively; P=0.006).

With median follow up of 7.1 years (IQR 5.5-8.2), median OS and EFS were 4.6 years (95%CI 3.4-6.5) and 1.3 years (95%CI 1.0-1.7), respectively. Estimated 5-year OS for ALK+ ALCL, ALK- ALCL, PTCL-TFH, and PTCL-NOS were 86% (95%CI 76-98%), 72% (95%CI 61-85%), 48% (95%CI 39-59%), and 26% (95%CI 20-35%), respectively; estimated 5-year EFS were 75% (95%CI 63-90%), 54% (95%CI 43-69%), 30% (95%CI 22-40%), and 16% (95%CI 11-24%), respectively. Comparing non-ALCL subtypes, median OS and EFS were 4.6 years (95%CI 3.1-7.7) and 1.1 years (95%CI 0.8-1.7), respectively, for PTCL-TFH vs 1.9 years (95%CI 1.4-2.9) and 0.7 years (95%CI 0.5-1.2), respectively, for PTCL-NOS. PTCL-TFH was associated with superior OS (HR 0.55; 95% CI, 0.40-0.76; P<0.001) and EFS (HR 0.66; 95% CI, 0.49-0.88; P=0.005) after multivariable adjustment for IPI and gender.

In total, 56%, 42%, and 27% of patients achieved EFS6, EFS12, and EFS24 in PTCL-NOS, compared to 78%, 48%, and 34% in PTCL-TFH, respectively. Estimated 5-year sOS for PTCL-NOS and PTCL-TFH were 41% (95%CI 31-53%) and 53% (95%CI 43-65%), respectively, for those achieving EFS6, 44% (95%CI 32-59%) and 68% (95%CI 56-82%), respectively, for those achieving EFS12, and 60% (95%CI 46-78%) and 82% (95%CI 70-97%), respectively, for those achieving EFS24. Among those failing early-event endpoints, PTCL-TFH was associated with improved estimated 5-year sOS as compared with PTCL-NOS: 18% (95%CI 6-56%) vs 5% (95%CI 1-18%), respectively, for EFS6 (HR 0.51; 95% CI, 0.27-0.96; P=0.036); 28% (95%CI 17-47%) vs 11% (95%CI 5-23%), respectively, for EFS12 (HR 0.52; 95%CI 0.34-0.82; P=0.004); 27% (95%CI 17-44%) vs 11% (95%CI 6-22%), respectively, for EFS24 (HR 0.57; 95% CI, 0.38-0.85; P=0.006).

Conclusions

The LEO prospective cohort delineates the evolving outcomes of PTCL nodal subtypes in the modern era. While non-ALCL nodal subtypes continue to have inferior survival compared to ALCL, PTCL-TFH has improved outcomes compared to PTCL-NOS, representing a unique clinical subtype with divergent pathogenesis and treatment responses. In addition, patients with PTCL-TFH with early relapses who fail EF6 and EFS12 appear to do better than those with PTCL-NOS at time of relapse, reflecting likely biological differences in responses to salvage treatment sequencing (NCT02736357).