Duvelisib Induces Deep Responses in Peripheral T-Cell Lymphoma: Final Results of the Phase II PRIMO Trial of Duvelisib in Relapsed/Refractory Peripheral T-Cell Lymphoma

Author(s): Neha Mehta-Shah, MD, MSci¹; Pier Luigi Zinzani, MD, PhD^2,3; Eric D. Jacobsen, MD⁴; Jasmine Zain, MD⁵; Monica Mead, MD^6,7; Carla Casulo, MD⁸; Giuseppe Gritti, MD, PhD⁹; Lauren Pinter-Brown, MD¹⁰; Koji Izutsu, MD, PhD¹¹; David Sidransky, MD¹²; Ohad S. Bentur, MD¹³; Barbara Pro, MD¹⁴; Christopher P. Fox, PhD, MBChB(Hons), FRCP, FRCPath¹⁵; Jonathan E. Brammer, MD¹⁶; Steven M. Horwitz, MD¹⁷;

Source: DOI: 10.1200/JCO-25-03120

Dr. Anjan Patel's Thoughts

This was a reassuring finding for standard risk nontransplant patients with deep sustained responses, esp those having issues taking lenalidomide. I would be cautious in extrapolating this to high risk or post-transplant patients. This study makes the fixed duration therapy idea more palatable for many of us.

PURPOSE

Peripheral T-cell lymphomas (PTCLs) are rare, heterogeneous, aggressive lymphomas. Five-year overall survival (OS) remains approximately 30%-40%, and most patients will develop relapsed or refractory (R/R) disease. Duvelisib is an oral dual inhibitor of phosphatidylinositol 3-kinase (PI3K)-δ and PI3K-γ isoforms. Here, we report on the final analysis of the phase II PRIMO trial (ClinicalTrials.gov identifier: NCT03372057; Secura Bio, Inc) evaluating duvelisib monotherapy in R/R PTCL.

METHODS

PRIMO was conducted in two phases (dose optimization and dose expansion [PRIMO-EP]) 45 centers globally. Eligible patients were age 18 years and older, had histologically confirmed diagnosis of PTCL, and had received ≥2 cycles of one standard regimen for PTCL. Based on dose optimization results, the selected regimen for PRIMO-EP was 75 mg twice a day for two cycles (to maximize disease control) followed by 25 mg twice a day (to reduce late toxicities), continued until progressive disease or unacceptable toxicity.

RESULTS

PRIMO-EP (N = 123) outcomes included independent review committee–assessed objective response rate (ORR): 48.0%, complete response rate (CRR): 33.3%, median progression-free survival (mPFS): 3.4 months, median OS (mOS): 12.4 months, and median duration of response (mDOR): 7.9 months. In the angioimmunoblastic T-cell lymphoma (AITL) subgroup, outcomes were ORR: 62.2%, CRR: 51.4%, mPFS: 8.3 months, mOS: 18.1 months, and mDOR: 11.3 months. Treatment-emergent adverse events (TEAEs; any grade) occurred in 120 patients (97.6%), and TEAEs grade ≥3 occurred in 91 patients (74.0%). TEAEs resulting in dose hold or dose reduction occurred in 44.7% and 9.8% of patients, respectively.

CONCLUSION

The PRIMO study demonstrates significant activity and tolerability of duvelisib in patients with R/R PTCL, most notably in the AITL subgroup. This provides strong rationale for further development in PTCL, and more specifically in the subgroup of nodal T-follicular helper cell lymphoma.

Author Affiliations

¹Washington University School of Medicine in St. Louis, Saint Louis, MO; ²IRCCS Azienda Ospedalierao-Universitaria di Bologna Istituto di Ematologia “Seràgnoli”, Bologna, Italy; ³Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy; ⁴Dana-Farber Cancer Institute, Boston, MA; ⁵Lymphoma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY; ⁶Division of Hematology/Oncology, University of California, Los Angeles (UCLA), Los Angeles, CA; ⁷Clinical Research Solutions, ProPharma Group, Raleigh, NC; ⁸University of Rochester Medical Center – James P. Wilmot Cancer Institute, Rochester, NY; ⁹Hematology and Bone Marrow Transplant Unit, ASST Papa Giovanni XXIII, Bergamo, Italy; ¹⁰University of California—Irvine, Irvine, CA; ¹¹National Cancer Center Hospital, Tokyo, Japan; ¹²Johns Hopkins University, Baltimore, MD; ¹³Secura Bio, Inc, Berkeley Heights, NJ; ¹⁴Columbia University Herbert Irving Comprehensive Cancer Center, New York, NY; ¹⁵School of Medicine, University of Nottingham, Nottingham, United Kingdom; ¹⁶Division of Hematology, Department of Internal Medicine, The Ohio State University, Columbus, OH; ¹⁷Memorial Sloan Kettering Cancer Center, New York, NY

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