NCCN Adds Duvelisib to Clinical Practice Guidelines for CTCL

The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology have been updated to include duvelisib (Copiktra) as a category 2A treatment option for cutaneous T-cell lymphoma (CTCL), including mycosis fungoides and Sézary syndrome (MFSS).¹

“We are very pleased to see duvelisib added as a treatment option in the NCCN Guidelines for patients with CTCL (MFSS). We appreciate NCCN’s recognition of evidence showing [duvelisib], as an oral dual PI3K inhibitor, to be a clinically important option in the treatment of T cell lymphomas,” said Christiane Langer, senior vice president, head of Clinical and Medical Affairs at Secura Bio, in a news release.¹ “Currently we are advancing a [p]hase 3 trial [TERZO; NCT06522737] evaluating [duvelisib] in patients with relapsed/refractory [R/R] nodal T-cell lymphoma with a T follicular helper (TFH) phenotype. We look forward to building the clinical evidence that further defines [duvelisib]’s role across T-cell lymphomas where successful treatment options have proven challenging.”

Duvelisib is currently indicated for the treatment of patients with relapsed/refractory (R/R) chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) after at least 2 prior therapies; clinical investigations in T-cell lymphoma remain ongoing.

In 2018, the FDA granted duvelisib full approval in R/R CLL/SLL and accelerated approval in R/R follicular lymphoma, supported by the phase 3 DUO (NCT02004522) and phase 2 DYNAMO trials (NCT01882803). As the treatment landscape in follicular lymphoma had evolved since the approval, duvelisib’s approval in the indication was later voluntarily withdrawn in 2021 by Secura Bio, who then pivoted duvelisib’s clinical development strategy to focus on T-cell lymphoma.

Duvelisib in T-Cell Lymphoma

Duvelisib earned an orphan drug designation in T-cell lymphoma from the FDA in 2019 during its clinical investigation in the phase 2 PRIMO trial (NCT03372057). Here, patients with R/R peripheral T-cell lymphoma received duvelisib at 75 mg twice daily, followed by 25 mg twice daily.² Final data from dose expansion (n = 123) showed an overall response rate (ORR) of 48% and complete response rate (CRR) of 33% with duvelisib treatment. The preliminary safety profile was considered reasonable for PTCL and consistent with previous reports.

The agent also holds an earlier fast track designation in PTCL and is an NCCN-recommended treatment in the R/R setting.

With the favorable results from PRIMO, the randomized phase 3 TERZO trial is currently evaluating duvelisib as monotherapy in patients with R/R nodal T-cell lymphoma with a T follicular helper (TFH) phenotype against investigator’s choice of gemcitabine or bendamustine.^3,4 The primary end point of the study is independent review committee-assessed progression-free survival; secondary end points include overall survival (OS), investigator-assessed PFS, ORR, CRR, duration of response, safety, and quality of life.

The trial is accruing up to 124 patients across 43 sites in Europe. Patients must have pathologically confirmed nodal T-cell lymphoma with TFH phenotype, including angioimmunoblastic T-cell lymphoma, follicular T-cell lymphoma, or other nodal PTCL, and must have progressed on at least 1 prior line of systemic anticancer therapy.

Safety Considerations

Safety concerns with duvelisib have been the subject of increased regulatory scrutiny in recent years. Notably, in 2022, the FDA issued a warning for patients with leukemia and lymphoma regarding a possible increased risk of death and serious adverse effects with duvelisib, including infections, diarrhea, inflammation of the intestines and lungs, skin reactions, and high liver enzyme levels in the blood. A listing of these toxicities are reflected in a boxed warning in duvelisib’s prescribing information.⁵

In the DUO trial, duvelisib’s adverse event profile was primarily characterized by diarrhea, neutropenia, pyrexia, nausea, anemia, and cough. One year after the FDA’s warning, a 5-year analysis of OS in the DUO trial indicated a “detriment” in OS.

The updated OS data led the FDA’s Oncologic Drug Advisory Committee (ODAC) to decide that the benefit-risk profile of duvelisib was unfavorable in R/R CLL/SLL, its current approved indication. Although Secura Bio maintained that the OS was comparable to previous data and that the safety profile has remained the same since approval, the ODAC majority voiced concerns regarding safety and inadequate dose optimization.

Ultimately, duvelisib’s recent inclusion in the NCCN Guidelines for T-cell lymphomas underscores its continued clinical relevance and evolving role in select T-cell lymphoma populations. In light of this safety discourse, continued vigilance is warranted when incorporating the agent into clinical practice.

REFERENCES

1. Secura Bio announces NCCN® duvelisib (COPIKTRA®) update to clinical practice guidelines in oncology for cutaneous T-cell lymphoma (CTCL), including mycosis fungoides and Sézary syndrome. News release. Secura Bio. December 17, 2025. Accessed December 18, 2025. https://tinyurl.com/7bxyc2v9

2. Mehta-Shah N, Zinzani PL, Jacobsen ED, et al. Duvelisib in patients with relapsed/refractory peripheral T-cell lymphoma: final results from the phase 2 PRIMO trial. Blood. 2024;144(Supplement 1):3061-3061. doi:blood-2024-203577

3. A study of duvelisib versus gemcitabine or bendamustine in participants with relapsed/refractory nodal T cell lymphoma with T follicular helper (TFH) phenotype (TERZO). ClinicalTrials.gov. Updated December 12, 2025. Accessed December 18, 2025. https://www.clinicaltrials.gov/study/NCT06522737

4. Cwynarski K, Domenech ED, Sidransky D, et al. A multicenter, open-label, phase 3, randomized controlled trial of duvelisib versus investigator’s choice of gemcitabine or bendamustine in patients with relapsed/refractory nodal T cell lymphoma with T follicular helper phenotype. Blood. 2024;144(Supplement 1):3074.1-3074.1. doi:10.1182/blood-2024-203290

5. Copiktra (duvelisib). US FDA. Updated September 2018. Accessed December 18, 2025. https://tinyurl.com/3fdvbh4s