Efficacy of idelalisib in CLL subpopulations harboring del(17p) and other adverse prognostic factors: Results from a phase 3, randomized, double-blind, placebo-controlled trial.

Leukemia, Myelodysplasia, and Transplantation
Session Type and Session Title: 
Poster Highlights Session, Leukemia, Myelodysplasia, and Transplantation
Abstract Number: 
J Clin Oncol 32:5s, 2014 (suppl; abstr 7011^)
Jeff Porter Sharman, Steven E. Coutre, Richard R. Furman, Bruce D. Cheson, John M. Pagel, Peter Hillmen, Jacqueline Claudia Barrientos, Andrew David Zelenetz, Thomas J. Kipps, Ian Flinn, Paolo Ghia, Michael J. Hallek, Bertrand Coiffier, Susan Mary O'Brien, Eugen Tausch, Karl A Kreuzer, Wendy Jiang, Thomas Michael Jahn, Mirella Lazarov, Stephan Stilgenbauer; Willamette Valley Cancer Institute and Research Center/US Oncology Research, Springfield, OR; Stanford Cancer Center, Stanford University School of Medicine, Stanford, CA; Weill Cornell Medical College, New York, NY; Georgetown University Medical Center, Washington, DC; Fred Hutchinson Cancer Research Center, Seattle, WA; The Leeds Teaching Hospitals, St. James Institute of Oncology, Leeds, United Kingdom; Hofstra North Shore-LIJ School of Medicine, Hempstead, NY; Memorial Sloan Kettering Cancer Center, New York, NY; University of California, San Diego, School of Medicine, San Diego, CA; Sarah Cannon Research Institute, Nashville, TN; Università Vita e Salute; San Raffaele Scientific Institute, Milano, Italy; University of Cologne, Cologne, Germany; Lyon Sud University Hospital, Pierre-Bénite, France; The University of Texas MD Anderson Cancer Center, Houston, TX; Ulm University, Ulm, Germany; University Hospital Cologne, Cologne, Germany; Gilead Sciences, Foster City, CA

Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).

Abstract Disclosures


Background: Idelalisib (IDELA) is a potent and selective inhibitor of PI3Kδ, which is critical for activation, proliferation and survival of B cells and their homing and retention in lymphoid tissues. An unmet need exists for effective therapies in patients with CLL positive for del(17p) and other adverse prognostic factors. This report describes the efficacy of IDELA in combination with rituximab (R) in such high-risk relapsed patients. Methods: Samples for del(17p), del(11q), TP53mut, IGHVmut, ZAP70 and CD38 expression, and β2-microglobulin were collected prospectively and tested using standard methods. Patients were stratified based on presence of del(17p) and/or TP53mut, and on IGHV mutational status. The endpoints evaluated in the high-risk subpopulations in the preplanned 1st interim analysis include progression-free-survival (PFS) and overall response rate (ORR). The primary study analysis was reported in NEJM 2014. Results: IDELA+R retained robust efficacy across all high-risk subpopulations (see Table). Importantly, IDELA+R achieved 76.5% ORR and PFS HR 0.13 in the highest risk patients who were positive for both del(17p) and TP53mut, compared to 80.4% ORR and PFS HR 0.17 in those who had neither present. Conclusions: These results confirm the retained robust efficacy of IDELA in high-risk CLL subpopulations and support IDELA as a potentially important novel treatment for patients with CLL positive for del(17p) and other adverse prognostic factors. Clinical trial information: NCT01539512.

HR 95%CI n %ORR n %ORR
Overall 0.15 0.08,0.28 88 80.7 88 12.5
Rai stage III or IV 0.12 0.05,0.27 52 75.0 60 11.7
Binet Stage C 0.13 0.06,0.30 47 74.5 51 13.7
Del(17p) 0.14 0.04,0.47 20 80.0 24 0.0
TP53mut 0.11 0.04,0.31 34 79.4 30 10.0
Del(17p) and/or TP53mut
: Both 0.13 0.04,0.47 17 76.5 15 0.0
: Either one alone 0.09 0.02,0.42 20 85.0 24 12.5
: Neither 0.17 0.07,0.43 51 80.4 49 16.3
Del(11q) 0.10 0.02,0.46 28 82.1 29 6.9
IGHV unmutated 0.13 0.06,0.27 71 78.9 72 12.5
ZAP70+ 0.13 0.06,0.26 77 79.2 74 12.2
CD38+ 0.13 0.05,0.34 43 83.7 34 17.6
β2-microglobulin > 4mg/L 0.14 0.07,0.27 75 77.3 68 10.3