The phase 3 DUO trial: Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL

Ian W. Flinn, Peter Hillmen, Marco Montillo, Zsolt Nagy, Árpád Illés, Gabriel Etienne, Julio Delgado, Bryone J. Kuss, Constantine S. Tam, Zoltán Gasztonyi, Fritz Offner, Scott Lunin, Francesco Bosch, Matthew S. Davids, Nicole Lamanna, Ulrich Jaeger, Paolo Ghia, Florence Cymbalista, Craig A. Portell, Alan P. SkarbnikAmanda F. Cashen, David T. Weaver, Virginia M. Kelly, Barry Turnbull, Stephan Stilgenbauer

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Abstract

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.

Original languageEnglish
Pages (from-to)2446-2455
Number of pages10
JournalBlood
Volume132
Issue number23
DOIs
Publication statusPublished - Dec 6 2018

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ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Flinn, I. W., Hillmen, P., Montillo, M., Nagy, Z., Illés, Á., Etienne, G., Delgado, J., Kuss, B. J., Tam, C. S., Gasztonyi, Z., Offner, F., Lunin, S., Bosch, F., Davids, M. S., Lamanna, N., Jaeger, U., Ghia, P., Cymbalista, F., Portell, C. A., ... Stilgenbauer, S. (2018). The phase 3 DUO trial: Duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. Blood, 132(23), 2446-2455. https://doi.org/10.1182/blood-2018-05-850461