Optimal treatment in patients with refractory or relapsed peripheral T-cell lymphomas (R/R T-NHL) is unknown. In this population-based study, outcome in R/R PTCL not otherwise specified (PTCL NOS), angioimmunoblastic T-cell lymphoma (AITL) and ALK+ and ALK- anaplastic large cell lymphoma (ALCL) was evaluated. Patients with PTCL NOS, AITL, ALK+ ALCL and ALK- ALCL (≥18 years) diagnosed in 2014-2019 were identified using the Netherlands Cancer Registry. Endpoints were overall response rate (ORR), progression-free survival (PFS) and overall survival (OS). The 2-year PFS of 821 patients was 57%. Among 311 patients with a relapse, 243 received second-line treatment: 44% salvage chemotherapy, 20% brentuximab vedotin (BV) and 36% other treatment. In third-line, BV was most commonly used (38%). ORR following second-line treatment was 47%. Two-year PFS and OS after relapse were 25% and 34%, respectively. Risk of second relapse was negatively affected by early relapse (<12 months post-diagnosis), while BV reduced this risk compared to salvage chemotherapy (HR 0.55; 0.35-0.87; p=0.01). Reduced risk of relapse was independent of histological subtype. The best outcomes were observed for patients treated with salvage chemotherapy receiving consolidative autologous and allogeneic stem cell transplantation (SCT) (2-year OS 68%), patients treated with BV achieving a second complete remission (2-year OS 74%) and patients with allogeneic SCT (2-year OS 60%). The risk of second relapse was significantly lower for R/R T-NHL patients treated with BV compared to patients treated with salvage chemotherapy, and this was irrespective of subtype. Therefore, the use of salvage chemotherapy for R/R T-NHL patients is challenged.
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