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TP53 aberrations in CLL
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Study/treatment Sponsors
Study 115:
a randomized, double-blind and placebo-controlled study of idelalisib in
combination with bendamustine and rituximab (BR) for previously treated CLL Idelalisib 150 mg BD plus BR versus BR
NCT01569295 Gilead Sciences
Study 119: a phase 3, randomized, controlled study evaluating the efficacy and safety
of idelalisib (GS-1101) in combination with ofatumumab for previously treated CLL
Idelalisib 150 mg BD + ofatumumab versus ofatumumab alone
NCT01659021 Gilead Sciences
A phase 2 open-label study of the efficacy
of ABT-199 (GDC-0199) in subjects with R/R
or previously untreated CLL harboring the
17p deletion
Venetoclax 400 mg OD NCT01889186
AbbVie Genentech, Inc.
Population
Adult patients with R/R CLL (n=416); PD within 36 months of last treatment Idelalisib + BR Median age (range): 62 (56–69)
ECOG score/ Karnofsky status: not reported Median prior regimens: 2 (1–4) Placebo plus BR Median age (range): 64 (56–70)
ECOG score/ Karnofsky status: not reported Median prior regimens: 2 (1–4)
Adult patients with R/R CLL (n=261); PD within 24 months of last treatment Idelalisib plus ofatumumab
Median age (range): 68 (61–74) Karnofsky status:
80 (80–90)
Median prior regimens: 3 (2–4) Ofatumumab alone Median age (range): 67 (62–74) Karnofsky status:
80 (80–90)
Median prior regimens: 3 (2–5)
Adult patients with R/R CLL with del(17p) (n=107)
Median age (range): 67 (37–85)
ECOG score n (%):
0: 42 (39%) 1: 56 (52%) 2: 9 (8%)
Median prior regimens (IQR): 2 (1–4)
TP53 aberrations at baseline
del(17p) and/or TP53 mutations
Idelalisib + BR: 69/207 (33%)
BR: 68/209 (33%)
Overall response
in del(17p)/TP53 mutated population
ORR in del(17p) patients treated with idelalisib
+ BR: 22/38 (58%)
ORR in del(17p) patients treated with BR: (9/40) 23%
PFS in del(17p)/ TP53 mutated population
Median PFS in del(17p) and/or TP53 patients treated with idelalisib + BR: 11.3 months
Median PFS in del(17p) and/or TP53 patients treated with BR: 8.3 months
OS in del(17p)/ TP53 mutated
population
Median OS in del(17p) and/or TP53 patients treated with idelalisib + BR: not reached at a median follow-up of 14 months
Median OS in del(17p) and/or TP53 patients treated with BR: 20.3 months
Median OS in del(17p) and/or TP53 patients treated with idelalisib + ofatumumab: 25.8 months
Median OS in del(17p) and/or TP53 patients treated with ofatumumab: 19.3 months
Safety (experimental arm, overall population)
Reference
Grade 3–5 AE
occurring in ≥5%
of patients:
Idelalisib + BR: Neutropenia (60%) Febrile neutropenia (23%) Placebo + BR: Neutropenia (47%) Thrombocytopenia (13%) (overall study population)
(118)
del(17p) and/or TP53 mutations
Idelalisib plus ofatumumab: 70/174 (40%)
Ofatumumab: 33/87 (38%)
ORR in del(17p) and/or TP53 patients treated with idelalisib plus ofatumumab:
not reported
ORR in del(17p) and/or TP53 patients treated with ofatumumab:
not reported
Median PFS in del(17p) and/or TP53 patients treated with idelalisib plus ofatumumab:
15.5 months
Median PFS in del(17p)
and/or TP53 patients treated with ofatumumab:
5.8 months
Grade 3–5 TEAE
occurring in ≥5% of patients treated with idelalisib plus ofatumumab:
Neutropenia (34%) Diarrhea (20%) Pneumonia (16%)
Anemia (14%)
Febrile neutropenia (12%) Thrombocytopenia (11%) Hypokalemia (8%)
Pyrexia (7%)
Dyspnea (6%) Hypertension (5%) Dehydration (5%) Fatigue (5%)
Grade 3–5 TEAE occurring in ≥5%
of patients treated with
ofatumumab: Neutropenia (16%) Pneumonia (8%) Thrombocytopenia (7%) Anemia (6%)
Fatigue (5%) (overall study population)
Grade 3–5 AE in del(17p) patients occurring in 76% of patients
(20, 96)
del(17p) 100%
TP53 mutated 60/107 (72%)
ORR in del(17p) patients: 79.4% (independent review committee
assessment)
Median PFS in del(17p) patients: not reached at a median follow-up of 12.1 months
Median OS in del(17p) patients: not reached at median follow-up of 12.1 months
(24, 119)
Grade 3–5 AE
occurring in ≥5% of patients:
Neutropenia (40%)
Anemia (18%) Thrombocytopenia (15%) Autoimmune hemolytic anemia (7%)
Febrile neutropenia (5%) Pneumonia (5%)
Immune thrombocytopenic purpura(5%)
Tumor lysis syndrome (5%) Leukopenia (5%)
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haematologica | 2018; 103(12)
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