Bone marrow biopsy revealed the presence of large, atypical lymphoma cells with vesicular nuclei and prominent nucleoli, infiltrating sinusoidal vessels (haematoxylin and eosin stain × 200).
The FDA has accepted a Biologics license application (BLA) for denileukin diftitox (I/ONTAK, Citius Pharmaceuticals) as a treatment option in patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL). This application is based on the findings of a phase 3 study (NCT01871727).
Denileukin diftitox is an engineered cytotoxic fusion protein combining interleukin-2 (IL-2) and diphtheria toxin. The fusion protein has a high affinity for IL-2 receptors expressed on the surface of malignant cells. Once bound, it is taken up by the cell, releasing diphtheria toxin in the cytoplasm causing cell death. I/ONTAK is a reformulation (purified version) of ONTAK that received FDA approval in 2008 in patients with CTCL. However, ONTAK was voluntarily withdrawn from the US markets in 2014. A phase III study investigated I/ONTAK’s efficacy and safety.
The multicentre, single-arm, open-label, phase III study enrolled CD25-positive patients with a histopathological diagnosis of CTCL. The eligibility criteria included ECOG 0 to 2, acceptable bone marrow function and life expectancy of at least 3 months. The participants received prior treatment for their disease and a washout period of at least a month before receiving their treatment.
The first part of the study was done to determine the optimal dose of I/ONTAK in 21 patients. The participants received daily doses of I/ONTAK from 6 µg/kg to 15 µg/kg and determined 9 µg/kg daily as the optimal dose. In the next part of the study, 91 patients with CTCL received I/ONTAK (9 µg/kg daily) for 5 consecutive days every 21-day cycle.
The independent review committee (IRC) found an objective response rate (ORR) of 36.2% (95% CI, 25.0%-48.7%) with I/ONTAK treatment in the primary efficacy analysis set (n=69 patients). Further, the median duration of the response (DOR) and time to response (TTR) was 6.5 and 1.41 months, respectively. In the efficacy analysis set (n=71) an ORR of 42.3% along with DOR and TTR of 5.7 months and 1.41 months were reported.
The target action date is set on September 28, 2023.
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