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.
2015; Lippincott Williams & Wilkins; Volume: 33; Issue: 15_suppl Linguagem: Inglês
10.1200/jco.2015.33.15_suppl.7011
ISSN1527-7755
AutoresJacqueline C. Barrientos, Steven Coutré, Sven de Vos, Ian W. Flinn, Nina D. Wagner‐Johnston, Marshall T. Schreeder, Jeff P. Sharman, Thomas E. Boyd, Kanti Roop, John P. Leonard, Bess Sorensen, Anthony Viggiano, Thomas M. Jahn, Richard R. Furman,
Tópico(s)Advanced Breast Cancer Therapies
Resumo7011 Background: IDELA is a first-in-class PI3Kδ inhibitor approved in combination with rituximab for pts with relapsed CLL. Methods: Pts with R/R CLL were treated continuously with 150 mg BID oral IDELA and a limited # of cycles (C) of CIT to evaluate safety and efficacy of combination regimens. Pts could enroll in extension study after 48 wks. Responses were evaluated by published criteria (Hallek 2008; Cheson 2012). Results: 114 pts (37F/77M) median (med) age 65 (range 41-87) yrs enrolled with: extensive prior therapies (med 3, range 1-9), refractory disease (51%), high risk Rai (60%), del17p/TP53 mutation (29%), del11q (13%), unmutated IGHV (79%). Med exposure was 14.6 (range 0-49) mos. 61 pts (54%) enrolled in extension study. 21 (34%) were continuing on study. Most common and select AEs independent of causality (any Grade/Gr ≥ 3): diarrhea/colitis (52%/19%), pyrexia (45%/4%), cough (37%/1%), nausea (29%/1%), fatigue (32%/4%), pneumonia (23%/15%), dyspnea (22%/3%), rash (21%/4%), pneumonitis (4%/4%). AST/ALT elevation Gr ≥ 3 was seen in 12%. Most common reasons for discontinuation were AEs (25%) or PD (25%). 2 pts discontinued due to AST/ALT elevation, 1 due to Richter’s transformation. 20 (18%) deaths were reported on study; 6 pts experienced PD before death. ORR was 82.5% in all pts, 70% in pts with del17p/TP53 mut, and 87% among pts without. SD/PD was reported in 10%/3%. Med overall PFS was 26.1 mos, 20.3 mos for pts with del17p/TP53 mut, and 36.8 mos for pts without. Med OS for all pts or pts with del17p/TP53 mut was not reached. Estimated OS at 36 mos was 73.1% for all pts, 57.3% for pts with del17p/TP53, and 78.3% for pts without. Conclusions: IDELA in combination with CIT shows a manageable safety profile without increased toxicities and has substantial clinical activity in heavily pretreated, refractory, and high-risk CLL including presence of del17p/TP53mutation. Phase 3 trials of IDELA with O or BR in pts with R/R CLL are ongoing (NCT01659021, NCT01732926). Clinical trial information: NCT01088048.Idelalisib +. Rituximab (R) N=19 Ofatumumab (O) N=21 Bendamustine (B) N=18 BR N=15 Fludarabine (F) (oral) N=12 Chlorambucil (Chl) N=15 ChlR N=14 8 wks up to 6 C up to 12 C
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