4/27/2023 0 Comments Booku phase 3 2018![]() 7 However, except for allogeneic stem cell transplantation, there is general consensus that current therapies for CLL/small lymphocytic lymphoma (SLL) are not curative, and most patients will ultimately die of their disease. 5, 6 Recently approved therapies targeting key pathways of CLL cell proliferation and survival, particularly Bruton tyrosine kinase (BTK), phosphatidylinositol 3-kinase δ (PI3K-δ), and BCL2, have greatly improved outcomes for CLL patients and have been integrated into the CLL treatment landscape. 4 The comparator agent for the DUO trial, ofatumumab, is a humanized anti-CD20 antibody with single-agent efficacy against refractory CLL and a US Food and Drug Administration–approved treatment option. 2, 3 Chemotherapy, specifically alkylating agents and purine analogs, and monoclonal CD20 antibody therapy have long represented the traditional backbone of frontline therapy. 1 The timing and selection of therapy is largely informed by multiple clinical and biological factors, specifically disease stage, presence of poor prognostic molecular features such as 17p13.1 deletions and TP53 mutations, and the general status of individual patients, many of whom are elderly with comorbid conditions precluding aggressive chemoimmunotherapy. This trial was registered at as #NCT02004522.Ĭhronic lymphocytic leukemia (CLL) is the most common adult lymphoproliferative disorder in Western countries, with >20 000 estimated new cases in the United States in 2017 and >4600 deaths. The DUO trial data support duvelisib as a potentially effective treatment option for patients with RR CLL/SLL. The most common adverse events were diarrhea, neutropenia, pyrexia, nausea, anemia, and cough on the duvelisib arm, and neutropenia and infusion reactions on the ofatumumab arm. The overall response rate was significantly higher with duvelisib (74% vs 45% P <. 0001), including those with high-risk chromosome 17p13.1 deletions and/or TP53 mutations (HR = 0.40 P =. The study met the primary study end point by significantly improving progression-free survival per independent review committee assessment compared with ofatumumab for all patients (median, 13.3 months vs 9.9 months hazard ratio = 0.52 P <. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (n = 160) or ofatumumab IV (n = 159). We report here the results of DUO, a global phase 3 randomized study of duvelisib vs ofatumumab monotherapy for patients with relapsed or refractory (RR) CLL/SLL. ![]() In a phase 1 study, duvelisib showed clinically meaningful activity and acceptable safety in CLL/SLL patients. PI3K-δ,γ signaling can promote B-cell proliferation and survival in clonal B-cell malignancies, such as chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase δ and γ (PI3K-δ,γ) being developed for treatment of hematologic malignancies.
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