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

(2018) BLOOD. 132(23). p.2446-2455
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Abstract
Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase delta and gamma (PI3K-delta,gamma) being developed for treatment of hematologic malignancies. PI3K-delta,gamma 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 = 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] = 0.52; P<.0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR = 0.40; P = .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. This trial was registered at www.clinicaltrials.gov as #NCT02004522.
Keywords
CHRONIC LYMPHOCYTIC-LEUKEMIA, INHIBITOR, IDELALISIB, PI3K-GAMMA, IBRUTINIB, CLL, FLUDARABINE, COMBINATION, THERAPY, PI3K-DELTA, GAMMA

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MLA
Flinn, Ian W et al. “The Phase 3 DUO Trial : Duvelisib Vs Ofatumumab in Relapsed and Refractory CLL/SLL.” BLOOD 132.23 (2018): 2446–2455. Print.
APA
Flinn, I. W., Hillmen, P., Montillo, M., Nagy, Z., Illes, A., Etienne, G., Delgado, J., et al. (2018). The phase 3 DUO trial : duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. BLOOD, 132(23), 2446–2455.
Chicago author-date
Flinn, Ian W, Peter Hillmen, Marco Montillo, Zsolt Nagy, Arpad Illes, Gabriel Etienne, Julio Delgado, et al. 2018. “The Phase 3 DUO Trial : Duvelisib Vs Ofatumumab in Relapsed and Refractory CLL/SLL.” Blood 132 (23): 2446–2455.
Chicago author-date (all authors)
Flinn, Ian W, Peter Hillmen, Marco Montillo, Zsolt Nagy, Arpad Illes, Gabriel Etienne, Julio Delgado, Bryone J Kuss, Constantine S Tam, Zoltan Gasztonyi, Fritz Offner, Scott Lunin, Francesco Bosch, Matthew S Davids, Nicole Lamanna, Ulrich Jaeger, Paolo Ghia, Florence Cymbalista, Craig A Portell, Alan P Skarbnik, Amanda F Cashen, David T Weaver, Virginia M Kelly, Barry Turnbull, and Stephan Stilgenbauer. 2018. “The Phase 3 DUO Trial : Duvelisib Vs Ofatumumab in Relapsed and Refractory CLL/SLL.” Blood 132 (23): 2446–2455.
Vancouver
1.
Flinn IW, Hillmen P, Montillo M, Nagy Z, Illes A, Etienne G, et al. The phase 3 DUO trial : duvelisib vs ofatumumab in relapsed and refractory CLL/SLL. BLOOD. 2018;132(23):2446–55.
IEEE
[1]
I. W. Flinn et al., “The phase 3 DUO trial : duvelisib vs ofatumumab in relapsed and refractory CLL/SLL,” BLOOD, vol. 132, no. 23, pp. 2446–2455, 2018.
@article{8593679,
  abstract     = {{Duvelisib (also known as IPI-145) is an oral, dual inhibitor of phosphatidylinositol 3-kinase delta and gamma (PI3K-delta,gamma) being developed for treatment of hematologic malignancies. PI3K-delta,gamma 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 = 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] = 0.52; P<.0001), including those with high-risk chromosome 17p13.1 deletions [del(17p)] and/or TP53 mutations (HR = 0.40; P = .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. This trial was registered at www.clinicaltrials.gov as #NCT02004522.}},
  author       = {{Flinn, Ian W and Hillmen, Peter and Montillo, Marco and Nagy, Zsolt and Illes, Arpad and Etienne, Gabriel and Delgado, Julio and Kuss, Bryone J and Tam, Constantine S and Gasztonyi, Zoltan and Offner, Fritz and Lunin, Scott and Bosch, Francesco and Davids, Matthew S and Lamanna, Nicole and Jaeger, Ulrich and Ghia, Paolo and Cymbalista, Florence and Portell, Craig A and Skarbnik, Alan P and Cashen, Amanda F and Weaver, David T and Kelly, Virginia M and Turnbull, Barry and Stilgenbauer, Stephan}},
  issn         = {{0006-4971}},
  journal      = {{BLOOD}},
  keywords     = {{CHRONIC LYMPHOCYTIC-LEUKEMIA,INHIBITOR,IDELALISIB,PI3K-GAMMA,IBRUTINIB,CLL,FLUDARABINE,COMBINATION,THERAPY,PI3K-DELTA,GAMMA}},
  language     = {{eng}},
  number       = {{23}},
  pages        = {{2446--2455}},
  title        = {{The phase 3 DUO trial : duvelisib vs ofatumumab in relapsed and refractory CLL/SLL}},
  url          = {{http://dx.doi.org/10.1182/blood-2018-05-850461}},
  volume       = {{132}},
  year         = {{2018}},
}

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