The National Comprehensive Cancer Network has updated its Clinical Practice Guidelines in Oncology to list duvelisib (Copiktra) as a category 2A treatment option for cutaneous T‑cell lymphoma, including mycosis fungoides and Sézary syndrome.
Secura Bio said it welcomed the inclusion and noted ongoing development of duvelisib in T‑cell lymphomas, including the randomized phase 3 TERZO trial in relapsed or refractory nodal T‑cell lymphoma with a T follicular helper phenotype.
Duvelisib is currently approved for relapsed or refractory chronic lymphocytic leukemia/small lymphocytic lymphoma after at least two prior therapies. The agent received full FDA approval in 2018 for R/R CLL/SLL and accelerated approval for R/R follicular lymphoma based on the phase 3 DUO and phase 2 DYNAMO trials; the follicular lymphoma indication was voluntarily withdrawn in 2021 as the company shifted focus to T‑cell lymphomas.
In T‑cell lymphoma development, duvelisib received orphan drug designation in 2019 and produced encouraging results in the phase 2 PRIMO trial. In the dose expansion cohort (n = 123), the overall response rate was 48% and the complete response rate 33%. The safety profile in PRIMO was described as consistent with prior reports for the drug.
The TERZO phase 3 study is comparing duvelisib monotherapy with investigator’s choice of gemcitabine or bendamustine in patients with relapsed or refractory nodal T‑cell lymphoma with TFH phenotype. The trial’s primary endpoint is independent review committee‑assessed progression‑free survival; secondary endpoints include overall survival, investigator‑assessed PFS, response rates, duration of response, safety, and quality of life. The study is enrolling up to 124 patients across multiple sites in Europe and requires prior progression on at least one line of systemic therapy.
Safety concerns have drawn regulatory scrutiny. In 2022 the FDA warned of a possible increased risk of death and serious adverse effects with duvelisib, including infections, severe diarrhea and colitis, pneumonitis, skin reactions, and elevated liver enzymes; these risks are reflected in a boxed warning. Common adverse events observed in the DUO trial included diarrhea, neutropenia, fever, nausea, anemia, and cough. A five‑year overall survival analysis from DUO signaled a detriment in OS, prompting the FDA’s Oncologic Drug Advisory Committee to judge the benefit‑risk profile unfavorable in R/R CLL/SLL.
Despite safety debates, duvelisib’s addition to the NCCN guidelines underlines its ongoing clinical relevance in select T‑cell lymphoma populations. Clinicians are advised to apply caution and close monitoring when considering the agent in practice.
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