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Multicenter Study
. 2025 Aug 26;9(16):4286-4305.
doi: 10.1182/bloodadvances.2025016347.

Real-world evidence of duvelisib and romidepsin in relapsed/refractory peripheral and cutaneous T-cell lymphomas

Josie G Ford  1   2 , Min Jung Koh  3 , Alexandra W Lenart  1 , Caroline MacVicar  1 , Kusha Chopra  1 , Arushi Meharwal  1 , Mark N Sorial  4 , Mwanasha Merrill  5   6 , Anna B Rider  7 , Aliyah R Sohani  7   8 , Sean M McCabe  1 , Ronnie A Nemec  1 , Makoto Iwasaki  1 , Dhruv Mistry  1 , Khyati Maulik Kariya  1 , Steven Chen  1   8   9 , Jeffrey Barnes  1   8 , Steven McAfee  1   8 , Yi-Bin Chen  1   8 , Corben Yuwai Wong  1 , Kristiana Nasto  1 , Eric Jacobsen  5   8 , Salvia Jain  1   8   10
Affiliations
Multicenter Study

Real-world evidence of duvelisib and romidepsin in relapsed/refractory peripheral and cutaneous T-cell lymphomas

Josie G Ford et al. Blood Adv. .

Abstract

Patients with relapsed or refractory (R/R) peripheral T-cell lymphomas (PTCL) require lineage-specific therapies to bridge to hematopoietic stem cell transplantation (HSCT). A previous phase 1/2 study of duvelisib/romidepsin (duv/romi) reported an overall response rate (ORR) of 58% and a complete response rate (CRR) of 42% with reduced grade 3 to 4 transaminitis (14%). We report real-world duv/romi outcomes in a multicenter, 38-patient R/R PTCL cohort. The median age at diagnosis was 62 years. Histological subtypes included nodal T follicular helper cell (nTFH; n = 17), PTCL-not otherwise specified (n = 14), cutaneous T-cell lymphoma (TCL; n = 3), extranodal natural killer/TCL (n = 1), ALK-negative anaplastic large cell lymphoma (n = 1), adult T-cell leukemia/lymphoma (n = 1), and hepatosplenic TCL (n = 1). The median previous therapy count was 1 (interquartile range [IQR], 1-2); 15 patients relapsed and 23 were refractory to prior treatment, including 8 prior HSCT (5 autologous, 3 allogeneic). After a median of 3 cycles (IQR, 2-4), ORR and CRR were 61% and 47%, respectively, with higher ORR (82% vs 43%) and CRR (71% vs 29%) in nTFH versus non-nTFH. The median progression-free survival and overall survival (HSCT-censored) were 11 and 16 months for nTFH, versus 3.3 and 8.3 months for non-nTFH. The median time to response was 1.9 months (IQR, 1.7-2.6), duration of response was 21 months, and time to next therapy was 17 months. After duv/romi, 11 patients bridged to allo-HSCT. Treatment was well tolerated; the most common grade 3 to 4 toxicities were lymphopenia (n = 15), neutropenia (n = 15), thrombocytopenia (n = 10), and transaminitis (n = 6), seldom leading to discontinuation (n = 4) or death (n = 1). These findings reinforce duv/romi's efficacy and bridging role to curative HSCT in high-risk R/R PTCL.

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Conflict of interest statement

Conflict-of-interest disclosure: M.N.S. reports research funding from Secura Bio and Daiichi Sankyo. E.J. reports research funding from Celgene, Merck, Pharmacyclics, and Hoffman-La Roche; honoraria from Merck, Daiichi Sankyo, Bristol Myers Squibb, and Bayer; and patents and royalties from UpToDate. S.J. reports consultancy for Mersana Therapeutics, Myeloid Therapeutics, SIRPant Immunotherapeutics, and Abcuro, Inc; research funding from SIRPant Immunotherapeutics, Abcuro, Inc, Daiichi Sankyo, and Acrotech Biopharma Inc; and membership on an entity’s board of directors or advisory committees for Mersana Therapeutics, Myeloid Therapeutics, SIRPant Immunotherapeutics, Abcuro, Inc, Secura Bio, Daiichi Sankyo, and CRISPR Therapeutics. The remaining authors declare no competing financial interests.

Figures

None
Graphical abstract
Figure 1.
Figure 1.
OS for real-world patients with R/R PTCL and CTCL receiving combination duv/romi. Kaplan-Meier curves show OS estimates since duv/romi treatment initiation. (A) Overall cohort with standard censoring. (B) Overall cohort with allo-HSCT after duv/romi as censoring events. (C) Comparison by histological subtype (nTFH vs non-nTFH) with standard censoring. (D) Comparison by histological subtype (nTFH vs non-nTFH) and allo-HSCT censored. P values calculated by log-rank test.
Figure 2.
Figure 2.
PFS for real-world patients with R/R PTCL and CTCL receiving combination duv/romi. Kaplan-Meier curves show PFS estimates since duv/romi treatment initiation. (A) Overall cohort with standard censoring. (B) Overall cohort with allo-HSCT after duv/romi as censoring events. (C) Comparison by histological subtype (nTFH vs non-nTFH) with standard censoring. (D) Comparison by histological subtype (nTFH vs non-nTFH) and HSCT censored. (E) Comparison by histological subtype (PTCL-NOS, nTFH subtype, and other) with standard censoring. (F) Comparison by histological subtype (PTCL-NOS, nTFH subtype, and other) and allo-HSCT censored. P values calculated by log-rank test.
Figure 3.
Figure 3.
OS for real-world patients with R/R PTCL and CTCL receiving combination duv/romi. Kaplan-Meier curves show OS estimates since duv/romi treatment initiation. (A) Comparison by best response (CR + PR) vs best response: progression (PD + SD) on duv/romi with standard censoring. (B) Comparison by best response (CR + PR) vs best response: progression (PD + SD) on duv/romi and allo-HSCT censored. P values calculated by log-rank test. PR, partial response; SD, stable disease.
Figure 4.
Figure 4.
EFS for real-world patients with R/R PTCL and CTCL receiving combination duv/romi. Kaplan-Meier curves show EFS estimates since duv/romi treatment initiation. (A) Overall cohort with standard censoring. (B) Overall cohort with allo-HSCT after duv/romi as censoring events. (C) Comparison by histological subtype (nTFH vs non-nTFH) with standard censoring. (D) Comparison by histological subtype (nTFH vs non-nTFH) and allo-HSCT censored. (E) Comparison by histological subtype (PTCL-NOS, nTFH subtype, and other) with standard censoring. (F) Comparison by histological subtype (PTCL-NOS, nTFH subtype, and other) and allo-HSCT censored. P values calculated by log-rank test. EFS, event-free survival.
Figure 5.
Figure 5.
Swimmer plot of patient outcomes over time for real-world patients with R/R PTCL and CTCL receiving combination duv/romi. Each horizontal bar represents an individual patient’s treatment timeline, with the x-axis denoting time (months since duv/romi treatment initiation) and the y-axis listing individual patients. Colored segments within the bars indicate different responses (blue denotes progression-free and gray denotes progression). Symbols indicate key clinical events (yellow square denotes complete response, dark blue triangle denotes allogeneic HSCT, and green line denotes alive patient status at the time of data cutoff). AITL, angioimmunoblastic T-cell lymphoma; ALCL, anaplastic large cell lymphoma; ALK–, anaplastic lymphoma kinase–negative; ATLL, adult T-cell leukemia/lymphoma; ENKTCL, extranodal natural killer/T-cell lymphoma; GD, gamma-delta; HSTCL, hepatosplenic T-cell lymphoma; MF, mycosis fungoides; SS, Sézary syndrome; w/nTFH, with nodal T follicular helper phenotype.
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References

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