Safety and Effectiveness of Denileukin Diftitox‐cxdl in Patients With Relapsed/Refractory Peripheral T‐Cell Lymphoma and Cutaneous T‐Cell Lymphoma: An All‐Case Post‐Marketing Study in Japan

Introduction

Denileukin diftitox (DD)‐cxdl, a fusion protein comprising diphtheria toxin fragments and human interleukin‐2, is a treatment for peripheral T‐cell lymphoma (PTCL) and cutaneous T‐cell lymphoma (CTCL). Previous trials have enrolled a limited number of patients, and there is a need to evaluate DD‐cxdl in a more diverse population, including those with different ages and treatment histories.

Methods

This observational post‐marketing study (19 May 2021 to 1 February 2024) was conducted in over 200 institutions in Japan to evaluate the safety and effectiveness of DD‐cxdl in patients with relapsed or refractory PTCL and CTCL (NCT05137847; jRCT2031220196). Patient characteristics, status of drug administration, adverse events (AEs), adverse drug reactions (ADRs), and effectiveness were assessed. Capillary leak syndrome was specified as an AE of special interest.

Results

Data from 104 patients were analyzed (PTCL: 85; CTCL: 19), including 57 male patients (54.8%). The median age was 74 (range: 20–88) years. The median number of prior chemotherapy lines was 3.5 (1.0–10.0), and approximately half (55.8%) of the patients discontinued treatment during cycle 1. Most patients experienced AEs (94.2%) and ADRs (84.6%), and the most common serious ADR was capillary leak syndrome (22.1%). Effectiveness could be assessed in 80/104 patients. The overall objective response rate was 16.3% (95% confidence interval: 8.9, 26.2), and in patients with PTCL and CTCL it was 15.4% (7.6, 26.5) and 20.0% (4.3, 48.1), respectively. Four patients (6.2%) with PTCL achieved a complete response.

Conclusions

This is the first observational study to evaluate the safety and effectiveness of DD‐cxdl in Japanese patients with relapsed or refractory PTCL and CTCL in daily clinical practice. No new safety concerns were identified. Clinicians should remain aware of the risk of capillary leak syndrome.

Trail Registration: ClinicalTrials.gov identifier: NCT05137847 and Japan Registry of Clinical Trials identifier: jRCT2031220196.