Final results of a phase 1b study of the safety and efficacy of the PI3Kδ inhibitor acalisib (GS-9820) in relapsed/refractory lymphoid malignancies

Blood Cancer Journal - Tập 8 Số 2
Arnon P. Kater1, Sanne H. Tonino1, Menno Spiering1, Martine E.D. Chamuleau2, Roberto Liu3, Adeboye H. Adewoye4, Jun Gao4, Lyndah Dreiling4, Yan Xin4, Jeanette K. Doorduijn5, Marie José Kersten6
1Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
2Department of Hematology, VU University Medical Center, Amsterdam, The Netherlands
3Clinical Trial Office Department of Hematology, Academic Medical Center, Amsterdam, The Netherlands
4Gilead Sciences, Inc., Foster City, CA, USA
5Department of Hematology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands
6Lymphoma and Myeloma Center (LYMMCARE), Academic Medical Center, Amsterdam, The Netherlands

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Shaffer, A. L., Rosenwald, A. & Staudt, L. M. Lymphoid malignancies: the dark side of B-cell differentiation. Nat. Rev. Immunol. 2, 920–932 (2002).

Eichhorst, B. F. et al. First-line therapy with fludarabine compared with chlorambucil does not result in a major benefit for elderly patients with advanced chronic lymphocytic leukemia. Blood. 114, 3382–3391 (2009).

Tallarico, M. et al. Toxicities and related outcomes of elderly patients (pts) (≥65 years) with hematologic malignancies in the contemporary era (Alliance A151611). Blood. 128, 536 (2016).

Shugg, R. P. et al. Effects of isoform-selective phosphatidylinositol 3-kinase inhibitors on osteoclasts: actions on cytoskeletal organization, survival, and resorption. J. Biol. Chem. 288, 35346–35357 (2013).

Cheson, B. D. et al. Revised response criteria for malignant lymphoma. J. Clin. Oncol. 25, 579–586 (2007).

Hallek, M. et al. Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute-Working Group 1996 guidelines. Blood. 111, 5446–5456 (2008).

Coutre, S. E. et al. Management of adverse events associated with idelalisib treatment: expert panel opinion. Leuk. Lymphoma. 56, 2779–2786 (2015).

Flinn, I. et al. A phase 1 evaluation of duvelisib (IPI-145), a PI3K-δ,γ inhibitor, in patients with relapsed/refractory iNHL. Blood. 124, 802 (2014).

Patnaik, A. et al. First-in-human phase I study of copanlisib (BAY 80-6946), an intravenous pan-class I phosphatidylinositol 3-kinase inhibitor, in patients with advanced solid tumors and non-Hodgkin’s lymphomas. Ann. Oncol. 27, 1928–1940 (2016).

Lampson, B. L. et al. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity. Blood. 128, 195–203 (2016).

Patel, M. R. et al. Early clinical activity and pharmacodynamic effects of duvelisib, a PI3Kδγ inhibitor, in patients with treatment naïve CLL. J. Clin. Oncol. 33, (2015) (Suppl; Abstr 7074).