Outcomes of PTCL patients failing first line therapy: International T-cell project analysis

An analysis of outcomes with patients with peripheral T-cell lymphoma (PTCL) who have failed first-line therapy was published online by Haematologica on 29 March 2018. The prospective study was part of the International T-cell Lymphoma Project (ITCLP) published by Monica Bellei, University of Modena and Reggio Emilia, Modena, Italy, and colleagues.

The ITCLP is led by the International T-Cell non-Hodgkin Lymphoma Study Group that is made up of a team of experts and worldwide institutions. The collaborative project aims to investigate T-cell lymphoma patient characteristics in order to have a better understanding of the factors that influence survival of patients.

A previous publication by the study group in the Journal of Clinical Oncology demonstrated that the World Health Organization (WHO) classification for defining PTCL and natural killer (NK)TCL was a useful tool however, diagnosis by experts was varied and in some cases led to misdiagnosis. The study authors recommended that diagnosis was still reviewed by an expert in hematopathology for accurate differentiation of PTCL and NKTCL subtypes. The importance of this being that patients receive the right treatment, which could lead to improved outcomes.

The current project (NCT01142674) is the largest cohort of prospectively collected international data on aggressive T-cell lymphoma. The aim was to improve the definition of clinical characteristics and therapies for common PTCL subtypes including (PTCL not otherwise specified (NOS)) and angioimmunoblastic T-cell lymphoma (AITL) and uncommon subtypes. This could therefore help to predict the prognosis of newly diagnosed patients. A primary outcome of the study was survival after relapse (SAR).

Key Findings

• N = 1,020 patients were included in the study with newly diagnosed disease enrolled between September 2006 and December 2015. Patients were treated accordingly to the current worldwide stands of care
• 937 patients who received first line treatment were identified as refractory (47%) or relapsed (21%)
• Median time from end of treatment to relapse was 8 months (range 2–73 months)
• Median follow up from relapsed/refractory (R/R) disease = 38 months (1–96)
  • It was noted that 440 patients died
• Median SAR was 5.8 months (95% CI, 4.9–7.2) overall
  • Median SAR for refractory patients = 5 months
  • Median SAR for relapsed patients = 11 months
• 3-year overall survival refractory patients (21%) vs relapsed (28%) P < 0.001
• 3-year SAR for patients receiving salvage bone marrow transplant (BMT) vs not receiving salvage BMT = 48% vs 18% (P < 0.001)

The authors also found that patients who had salvage therapy with HCT had better outcomes than patients who did not undergo this treatment (HR=0.36, 95% CI 0.26-0.48, P < 0.001). Refractory disease was associated with higher risk of death compared to relapsed disease. Additionally, there was longer SAR associated with later relapse than early relapse (HR=0.57, 95CI 0.41-0.79, P = 0.001). A univariate analysis demonstrated that in the first 24 months, patients with refractory disease had statistically significant poorer outcomes than relapsed patients (HR 1.50, 95% CI, 1.12–1.86, P < 0.001). However, after 24 months the outcomes were not significantly different.

From the study results, the authors found that patients with PTCL have “dismal outcomes” after relapse or disease progression. No significant difference was seen in outcomes in R/R patients between subtypes, apart from ALCL and ALK+. Outcomes were improved for patients who received transplant and there was better long term remission with later relapse undergoing high dose therapy and hematopoietic cell transplantation. However, due to refractory disease, early relapse and poor performance status, many patients are unable to have this kind of treatment.

The authors concluded that there is an “urgent need for novel agents and more effective salvage therapies”. Additionally, they hope that the results of this analysis will “provide a useful baseline on which to assess the efficacy of novel agents and therapies for R/R patients with T-cell lymphomas”.