DISCONTINUATION OF IDELALISIB TREATMENT DUE TO DISEASE PROGRESSION IN PATIENTS WITH RELAPSED AND REFRACTORY CLL: AN EVALUATION OF OUTCOMES
Author(s): ,
Jennifer R Brown
Affiliations:
Dana-Farber Cancer Institute,Boston,United States
,
Paolo Ghia
Affiliations:
Universita Vita-Salute San Raffaele and IRCCS San Raffaele Scientific Institute,Milan,Italy
,
Jeffrey A Jones
Affiliations:
Ohio State University,Columbus,United States
,
Andrew R Pettitt
Affiliations:
Department of Molecular and Clinical Cancer Medicine,University of Liverpool,Liverpool,United Kingdom
,
Jeff P Sharman
Affiliations:
US Oncology Network/Willamette Valley Cancer Institute,Springfield, Oregon,United States
,
Loic Ysebaert
Affiliations:
Department of Haematology,Institut Universitaire du Cancer de Toulouse - Oncopôle,Toulouse,France
,
Yeonhee Kim
Affiliations:
Gilead Sciences, Inc.,Foster City, CA,United States
,
Terry Newcomb
Affiliations:
Gilead Sciences, Inc.,Foster City, CA,United States
,
Nai-Shun Yao
Affiliations:
Gilead Sciences, Inc.,Foster City, CA,United States
,
Richard R Furman
Affiliations:
Weill Cornell Medical College,New York, NY,United States
Stephan Stilgenbauer
Affiliations:
University of Ulm,Ulm,Germany
(Abstract release date: May 19, 2016) EHA Learning Center. Brown J. Jun 10, 2016; 133203
Label: Abstracts 2016
Dr. Jennifer Brown
Dr. Jennifer Brown

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Abstract
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Abstract: P215

Type: Poster Presentation

Presentation during EHA21: On Friday, June 10, 2016 from 17:15 - 18:45

Location: Poster area (Hall H)

Background
There have been reports of rapid decline leading to death in patients with CLL following discontinuation of B-cell receptor pathway-targeted therapy (Jain, et al. Blood. 2015;125(13):2062-7).  Idelalisib (IDELA) is a first in class PI3Kδ inhibitor which inhibits multiple signaling pathways, including those downstream of the B-cell receptor, CXCR4, and CXCR5.  It is administered orally until disease progression or intolerance. Outcomes of patients with CLL who discontinued IDELA treatment either due to progressive disease (PD) or adverse events (AEs) have not been described comprehensively. 

Aims
The objective of this post hoc analysis was to examine the outcomes of patients with R/R CLL who discontinued IDELA.

Methods
Data were pooled for patients with R/R CLL who were randomized to treatment with either IDELA+ofatumumab (n=173) in Study 119 or IDELA+rituximab (n=110) in Study 116 (including long-term follow up in extension Study 117). Time-dependent endpoints were calculated from the dates of IDELA discontinuation, including: time to next therapy (TTNT), and time to death (TTD). Kaplan-Meier analysis was used to estimate overall survival (OS) from the date of randomization. Subgroup OS analyses were performed using the integrated safety data set.

Results
Of 283 patients in the safety population, 124 (44%) remained on IDELA, 28 (10%) discontinued due to PD (22 CLL progressions and 6 Richter’s transformations (RT), and 131 (46%) discontinued for reasons other than PD. Presence of -17p/TP53 mutation at baseline was reported for 54% of patients who discontinued due to PD, 41% of patients who discontinued due to AEs, and 37% of patients who remained on IDELA treatment. The clinical outcomes for those patients who discontinued IDELA treatment due to PD are tabulated.
 IDELA D/C due to PD(n=28)
OS, mos
Median (95% CI)18.8 (15.5, NR)
OS at 24 months, %44.4%
TTNT, mos
n7
Median (95% CI)0.9 (0.2, 3.7)
TTD, mos
n9
Median (95% CI)2.4 (0.1, 9.9)


Conclusion
In contrast to reports for other B-cell receptor pathway inhibitors, discontinuation of IDELA due to progression of CLL does not appear to be associated with shortened survival.

Session topic: CLL - Efficacy and safety of new treatments 1

Keyword(s): Chronic lymphocytic leukemia, Outcome measurement, Progression, Randomized
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