LONG-TERM FOLLOW-UP OF A PHASE IB TRIAL OF IDELALISIB IN COMBINATION WITH CHEMOIMMUNOTHERAPY (CIT) IN PATIENTS WITH RELAPSED/REFRACTORY (R/R) CLL INCLUDING PATIENTS WITH DEL17P/TP53 MUTATION
(Abstract release date: 05/21/15)
EHA Library. Barrientos J. 06/12/15; 100464; P210
Dr. Jacqueline Barrientos
Contributions
Contributions
Abstract
Abstract: P210
Type: Poster Presentation
Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45
Location: Poster area (Hall C)
Background
Idelalisib (IDELA) (Zydelig™) is a first-in-class PI3Kδ inhibitor approved in combination with rituximab for patients with relapsed CLL.
Aims
To determine the safety and clinical activity of idelalisib in combination with 6 commonly used chemo-immunotherapeutic agents for the treatment of R/R CLL.
Methods
Patients with R/R CLL were treated continuously with 150 mg BID oral IDELA and a limited number of cycles (C) of CIT to evaluate safety and efficacy of combination regimens. Patients could enroll in extension study after 48 weeks. Responses were evaluated by published criteria (Hallek 2008; Cheson 2012).
Results
114 patients (37F/77M) median age 65 (range 41-87) years enrolled with: extensive prior therapies (median: 3, range 1-9), refractory disease (51%), high-risk Rai (60%), del17p/TP53 mutation (29%), del11q (13%), unmutated IGHV (79%). Median exposure was 14.6 (range 0-49) months. 61 patients (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 patients discontinued due to AST/ALT elevation, 1 due to Richter’s transformation. 20 (18%) deaths were reported on study; 6 patients experienced PD before death. ORR was 82.5% in all patients, 70% in patients with del17p/TP53 mut, and 87% among patients without. SD/PD was reported in 10%/3%. Median overall PFS was 26.1 months, 20.3 months for patients with del17p/TP53 mut, and 36.8 months for patients without. Median OS for all patients or patients with del17p/TP53 mut was not reached. Estimated OS at 36 months was 73.1% for all patients, 57.3% for patients with del17p/TP53, and 78.3% for patients without.
Summary
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/TP53 mutation. Phase 3 trials of IDELA with O or BR in patients with R/R CLL are ongoing (NCT01659021, NCT01732926).
Keyword(s): Chronic lymphocytic leukemia, Clinical trial, PI3 kinase
Session topic: Chronic lymphocytic leukemia - Clinical 1
Type: Poster Presentation
Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45
Location: Poster area (Hall C)
Background
Idelalisib (IDELA) (Zydelig™) is a first-in-class PI3Kδ inhibitor approved in combination with rituximab for patients with relapsed CLL.
Aims
To determine the safety and clinical activity of idelalisib in combination with 6 commonly used chemo-immunotherapeutic agents for the treatment of R/R CLL.
Methods
Patients with R/R CLL were treated continuously with 150 mg BID oral IDELA and a limited number of cycles (C) of CIT to evaluate safety and efficacy of combination regimens. Patients could enroll in extension study after 48 weeks. Responses were evaluated by published criteria (Hallek 2008; Cheson 2012).
Results
114 patients (37F/77M) median age 65 (range 41-87) years enrolled with: extensive prior therapies (median: 3, range 1-9), refractory disease (51%), high-risk Rai (60%), del17p/TP53 mutation (29%), del11q (13%), unmutated IGHV (79%). Median exposure was 14.6 (range 0-49) months. 61 patients (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 patients discontinued due to AST/ALT elevation, 1 due to Richter’s transformation. 20 (18%) deaths were reported on study; 6 patients experienced PD before death. ORR was 82.5% in all patients, 70% in patients with del17p/TP53 mut, and 87% among patients without. SD/PD was reported in 10%/3%. Median overall PFS was 26.1 months, 20.3 months for patients with del17p/TP53 mut, and 36.8 months for patients without. Median OS for all patients or patients with del17p/TP53 mut was not reached. Estimated OS at 36 months was 73.1% for all patients, 57.3% for patients with del17p/TP53, and 78.3% for patients without.
Summary
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/TP53 mutation. Phase 3 trials of IDELA with O or BR in patients with R/R CLL are ongoing (NCT01659021, NCT01732926).
Keyword(s): Chronic lymphocytic leukemia, Clinical trial, PI3 kinase
Session topic: Chronic lymphocytic leukemia - Clinical 1
Abstract: P210
Type: Poster Presentation
Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45
Location: Poster area (Hall C)
Background
Idelalisib (IDELA) (Zydelig™) is a first-in-class PI3Kδ inhibitor approved in combination with rituximab for patients with relapsed CLL.
Aims
To determine the safety and clinical activity of idelalisib in combination with 6 commonly used chemo-immunotherapeutic agents for the treatment of R/R CLL.
Methods
Patients with R/R CLL were treated continuously with 150 mg BID oral IDELA and a limited number of cycles (C) of CIT to evaluate safety and efficacy of combination regimens. Patients could enroll in extension study after 48 weeks. Responses were evaluated by published criteria (Hallek 2008; Cheson 2012).
Results
114 patients (37F/77M) median age 65 (range 41-87) years enrolled with: extensive prior therapies (median: 3, range 1-9), refractory disease (51%), high-risk Rai (60%), del17p/TP53 mutation (29%), del11q (13%), unmutated IGHV (79%). Median exposure was 14.6 (range 0-49) months. 61 patients (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 patients discontinued due to AST/ALT elevation, 1 due to Richter’s transformation. 20 (18%) deaths were reported on study; 6 patients experienced PD before death. ORR was 82.5% in all patients, 70% in patients with del17p/TP53 mut, and 87% among patients without. SD/PD was reported in 10%/3%. Median overall PFS was 26.1 months, 20.3 months for patients with del17p/TP53 mut, and 36.8 months for patients without. Median OS for all patients or patients with del17p/TP53 mut was not reached. Estimated OS at 36 months was 73.1% for all patients, 57.3% for patients with del17p/TP53, and 78.3% for patients without.
Summary
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/TP53 mutation. Phase 3 trials of IDELA with O or BR in patients with R/R CLL are ongoing (NCT01659021, NCT01732926).
Keyword(s): Chronic lymphocytic leukemia, Clinical trial, PI3 kinase
Session topic: Chronic lymphocytic leukemia - Clinical 1
Type: Poster Presentation
Presentation during EHA20: From 12.06.2015 17:15 to 12.06.2015 18:45
Location: Poster area (Hall C)
Background
Idelalisib (IDELA) (Zydelig™) is a first-in-class PI3Kδ inhibitor approved in combination with rituximab for patients with relapsed CLL.
Aims
To determine the safety and clinical activity of idelalisib in combination with 6 commonly used chemo-immunotherapeutic agents for the treatment of R/R CLL.
Methods
Patients with R/R CLL were treated continuously with 150 mg BID oral IDELA and a limited number of cycles (C) of CIT to evaluate safety and efficacy of combination regimens. Patients could enroll in extension study after 48 weeks. Responses were evaluated by published criteria (Hallek 2008; Cheson 2012).
Results
114 patients (37F/77M) median age 65 (range 41-87) years enrolled with: extensive prior therapies (median: 3, range 1-9), refractory disease (51%), high-risk Rai (60%), del17p/TP53 mutation (29%), del11q (13%), unmutated IGHV (79%). Median exposure was 14.6 (range 0-49) months. 61 patients (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 patients discontinued due to AST/ALT elevation, 1 due to Richter’s transformation. 20 (18%) deaths were reported on study; 6 patients experienced PD before death. ORR was 82.5% in all patients, 70% in patients with del17p/TP53 mut, and 87% among patients without. SD/PD was reported in 10%/3%. Median overall PFS was 26.1 months, 20.3 months for patients with del17p/TP53 mut, and 36.8 months for patients without. Median OS for all patients or patients with del17p/TP53 mut was not reached. Estimated OS at 36 months was 73.1% for all patients, 57.3% for patients with del17p/TP53, and 78.3% for patients without.
Summary
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/TP53 mutation. Phase 3 trials of IDELA with O or BR in patients with R/R CLL are ongoing (NCT01659021, NCT01732926).
Keyword(s): Chronic lymphocytic leukemia, Clinical trial, PI3 kinase
Session topic: Chronic lymphocytic leukemia - Clinical 1
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