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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.
Abstracts that were granted an exception in accordance with ASCO's Conflict of Interest Policy are designated with a caret symbol (^).
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.
|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) and/or TP53mut|
|: Either one alone||0.09||0.02,0.42||20||85.0||24||12.5|
|β2-microglobulin > 4mg/L||0.14||0.07,0.27||75||77.3||68||10.3|
Abstracts by Jeff Porter Sharman:
Outcomes of patients with relapsed and refractory chronic lymphocytic leukemia (CLL) who discontinue idelalisib treatment.Meeting: 2016 ASCO Annual Meeting | Abstract No: 7531
Exposure-response analysis from a Phase 2 study of the Syk inhibitor entospletinib in patients with relapsed or refractory hematologic malignancies.Meeting: 2015 ASCO Annual Meeting | Abstract No: e13584
Long-term follow-up of a phase Ib trial of idelalisib (IDELA) in combination with chemoimmunotherapy (CIT) in patients (pts) with relapsed/refractory (R/R) CLL including pts with del17p/TP53 mutation.Meeting: 2015 ASCO Annual Meeting | Abstract No: 7011