International Assessment of Event-Free Survival at 24 Months and Subsequent Survival in Peripheral T-Cell Lymphoma

Abstract

Purpose Peripheral T-cell lymphomas (PTCLs) have aggressive clinical behavior. We have previously shown that event-free survival (EFS) at 24 months (EFS24) is a clinically useful end point in diffuse large B-cell lymphoma. Here, we assess EFS24 and subsequent overall survival (OS) in large, multinational PTCL cohorts. Patients and Methods Patients with systemic PTCL newly diagnosed from 2000 to 2012 and treated with curative intent were included from the United States and Sweden (initial cohorts) and from Canada (replication cohort). EFS was defined as time from date of diagnosis to progression after primary treatment, retreatment, or death. Subsequent OS was measured after achieving EFS24 or from the time of progression if it occurred within 24 months. OS rates were compared with the age-, sex-, and country-matched general population. Results Seven hundred seventy-five patients were included in the study (the median age at diagnosis was 64 years; 63% were men). Results were similar in the initial and replication cohorts, and a combined analysis was undertaken. Sixty-four percent of patients progressed within the first 24 months and had a median OS of only 4.9 months (5-year OS, 11%). In contrast, median OS after achieving EFS24 was not reached (5-year OS, 78%), although relapses within 5 years of achieving EFS24 occurred in 23% of patients. Superior outcomes after achieving EFS24 were observed in younger patients (≤ 60 years of age: 5-year OS, 91%). Conclusion EFS24 stratifies subsequent outcome in PTCL. Patients with PTCL with primary refractory disease or early relapse have extremely poor survival. However, more than one third of patients with PTCL remain in remission 2 years after diagnosis with encouraging subsequent OS, especially in younger patients. These marked differences in outcome suggest that EFS24 has utility for patient counseling, study design, and risk stratification in PTCL.

Fig 1.

Overall survival (OS) based on 24-month event-free survival (EFS24) in initial and replication cohorts. (A) Subsequent OS of patients who did not achieve EFS24 (progression within 24 months after diagnosis) in the Molecular Epidemiology Resource (MER) and Sweden (SWE). (B) Subsequent OS of patients who achieved EFS24 in the MER and SWE cohorts. (C) Subsequent OS of patients who did not achieve EFS24 in the British Columbia Cancer Agency (BCCA) replication cohort. (D) Subsequent OS of patients who achieved EFS24 in the BCCA cohort. PTCL, peripheral T-cell lymphoma.

Fig 2.

Overall survival (OS) based on 24-month event-free survival (EFS24) in combined cohorts (n = 775). (A) Subsequent OS of patients who did not achieve EFS24. (B) Subsequent OS of patients who achieved EFS24. SMR, standardized mortality ratio.

Fig 3.

Disease relapse in patients with peripheral T-cell lymphoma (PTCL) after achieving 24-month event-free survival (EFS24). (A) Estimated 5-year cumulative incidence of relapse or progression after achieving EFS24. The competing risk of death as a result of other or unknown causes is also shown. (B) Subsequent overall survival (OS) after relapse after initially achieving EFS24.

Fig 4.

Subsequent overall survival after achieving 24-month event-free survival (EFS24) stratified by the following pathologic subtypes: (A) angioimmunoblastic T-cell lymphoma; (B) anaplastic lymphoma kinase–negative anaplastic large-cell lymphoma; (C) peripheral T-cell lymphoma, not otherwise specified; and (D) other peripheral T-cell lymphoma subtypes.

Fig A1.

Event-free survival (A) and overall survival (B) in patients with peripheral T-cell lymphoma by cohort. BCCA, British Columbia Cancer Agency; MER, Molecular Epidemiology Resource.

Fig A2.

Event-free survival (A) and overall survival (B) in patients with peripheral T-cell lymphoma (PTCL) by subtype. AITL, angioimmunoblastic T-cell lymphoma; ALCL, anaplastic large-cell lymphoma; ALK, anaplastic lymphoma kinase; NOS, not otherwise specified.

Fig A3.

Overall survival after achieving 24-month event-free survival (EFS24) in (A) patients age ≤ 60 years and (B) patients receiving autologous stem-cell transplantation in first remission. PTCL, peripheral T-cell lymphoma.