TY - JOUR
T1 - The phase 3 DUO trial
T2 - Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL
AU - Flinn, Ian W.
AU - Hillmen, Peter
AU - Montillo, Marco
AU - Nagy, Zsolt
AU - Illés, Árpád
AU - Etienne, Gabriel
AU - Delgado, Julio
AU - Kuss, Bryone J.
AU - Tam, Constantine S.
AU - Gasztonyi, Zoltán
AU - Offner, Fritz
AU - Lunin, Scott
AU - Bosch, Francesco
AU - Davids, Matthew S.
AU - Lamanna, Nicole
AU - Jaeger, Ulrich
AU - Ghia, Paolo
AU - Cymbalista, Florence
AU - Portell, Craig A.
AU - Skarbnik, Alan P.
AU - Cashen, Amanda F.
AU - Weaver, David T.
AU - Kelly, Virginia M.
AU - Turnbull, Barry
AU - Stilgenbauer, Stephan
N1 - Publisher Copyright:
© 2018 by The American Society of Hematology
PY - 2018/12/6
Y1 - 2018/12/6
N2 - Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase d and g (PI3K-d,g) being developed for treatment of hematologic malignancies. PI3K-d,g signaling can promote B-cell proliferation and survival in clonal B-cell malignancies, such as chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In a phase 1 study, duvelisib showed clinically meaningful activity and acceptable safety in CLL/SLL patients. 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. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (n 5 160) or ofatumumab IV (n 5 159). 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 [HR] 5 0.52; P < .0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR 5 0.40; P 5 .0002). The overall response rate was significantly higher with duvelisib (74% vs 45%; P < .0001) regardless of del(17p) status. 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 DUO trial data support duvelisib as a potentially effective treatment option for patients with RR CLL/SLL.
AB - Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase d and g (PI3K-d,g) being developed for treatment of hematologic malignancies. PI3K-d,g signaling can promote B-cell proliferation and survival in clonal B-cell malignancies, such as chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). In a phase 1 study, duvelisib showed clinically meaningful activity and acceptable safety in CLL/SLL patients. 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. Patients were randomized 1:1 to oral duvelisib 25 mg twice daily (n 5 160) or ofatumumab IV (n 5 159). 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 [HR] 5 0.52; P < .0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR 5 0.40; P 5 .0002). The overall response rate was significantly higher with duvelisib (74% vs 45%; P < .0001) regardless of del(17p) status. 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 DUO trial data support duvelisib as a potentially effective treatment option for patients with RR CLL/SLL.
UR - http://www.scopus.com/inward/record.url?scp=85056697569&partnerID=8YFLogxK
U2 - 10.1182/blood-2018-05-850461
DO - 10.1182/blood-2018-05-850461
M3 - Article
C2 - 30287523
AN - SCOPUS:85056697569
SN - 0006-4971
VL - 132
SP - 2446
EP - 2455
JO - Blood
JF - Blood
IS - 23
ER -