Study design
The iLLUMINATE study was an open-label, multicentre, randomised phase III study comparing the treatment regimens IMBRUVICA® and obinutuzumab (IMBRUVICA® + O) vs. chlorambucil and obinutuzumab (CO) in firstline CLL/SLL patients ≥65 years old or <65 years old with coexisting conditions.[1]
Median age[1]
IMBRUVICA® + O cohort
70 years
(66-75)
CO cohort
72 years
(66-77)
Key patient eligibility criteria:[1]
- Treatment-naïve CLL/SLL requiring therapy
- Unsuitable for FCR due to ≥65 years OR <65 years with coexisting conditions
- CrCL <70 mL/min
- CIRS >6
The iLLUMINATE study included patients with high-risk features[1]
High-risk features included TP53 mutation, del(11q), del(17p) and/or unmutated uIGHV
Baseline characteristics[1]
Characteristic | IMBRUVICA® + O | CO |
| Median age (range), years ≥65 years, n (%) | 70 (66–75) 91 (81) | 72 (66–77) 92 (79) |
Female, n (%) | 46 (41) | 37 (32) |
| Ethnicity White Black or African-American Asian Native Hawaiian or other Pacific Islander | 109 (96) 2 (2) 1 (1) 1 (1) | 111 (96) 2 (2) 2 (2) 1 (1) |
| ECOG performance status 0 1 2 | 57 (50) 52 (46) 4 (4) | 53 (46) 56 (48) 7 (6) |
| Diagnosis Chronic lymphocytic leukaemia Small lymphocytic lymphoma | 107 (95) 6 (5) | 107 (92) 9 (8) |
Rai stage III or IV | 60 (53) | 59 (51) |
Bulky disease ≥5 cm, n (%) | 30 (27) | 44 (38) |
| High-risk features Del17p, TP53 mutation, del11q, or unmutated IGHV Del17p or TP53 mutation Del17p TP53 mutation* Del11q† Unmutated IGHV | 73 (65) 18 (16) 14 (12) 13/112 (12) 13 (12) 66/107 (62) | 75 (65) 23 (20) 18 (16) 16/110 (15) 22 (19) 57/107 (53) |
| Cytopenia baseline Any cytopenia Haemoglobin 11 g/dL or less Platelet count 100 x 109/L or less Absolute neutrophil count 1.5 x 109 cells/L or less | 63 (56) 51 (45) 28 (25) 7 (6) | 62 (53) 50 (43) 22 (19) 4 (3) |
Median absolute lymphocyte count x 109 cells/L | 59.7 (28.4–118.8) | 48.9 (14.4–101.3) |
| Cumulative illness rating scale for geriatric score Median >6 | 4.0 (2.0–7.0) 37 (33) | 4.0 (2.0–7.0) 36 (31) |
| Creatinine clearance Median, mL/min <60 mL/min | 72.0 (61.2–94.2) 26 (23) | 69.6 (55.8–89.4) 38 (33) |
Median time from initial diagnosis, months | 29.6 (10.5–55.6) | 36.5 (11.8–71.7) |
Data are median (IQR), n (%), or n/N (%).
6 x 28-day cycles of:
Obinutuzumab
1000 mg on Days 1, 8 and 15 of cycle 1 (first dose divided between Day 1 [100 mg] and Day 2 [900 mg])
1000 mg on Day 1 of cycles 2–6
(n=113)
and
IMBRUVICA®
420 mg once daily
until disease progression or unacceptable toxicity[1]
.png?width=1280&height=720&format=webp&quality=50 "Randomised 1:1")
6 x 28-day cycles of:
Chlorambucil
0.5 mg/kg on Days 1 and 15
Obinutuzumab
1000 mg on Days 1, 8 and 15 of cycle 1 (first dose divided between Day 1 [100 mg] and Day 2 [900 mg])
1000 mg on Day 1 of cycles 2–6
(n=116)[1]
Primary endpoint[1]
PFS
Secondary endpoints[1]
PFS in high-risk population, ORR, MRD, OS, IRR, safety, proportion of patients with sustained haemoglobin or platelet improvement
40.7 months
extended median follow-up[2]
CLL patient subgroups
uIGHV patients
Genetic aberration patients
Fit patients
Relapsed / refractory patients
Back to IMBRUVICA® studies
*Irrespective of del(17p) (4/112 patients in the IO group and 5/110 patients in the CO group had TP53 mutations in the absence of del[17p]).[1]
†Without del(17p) (hierarchical categories according to Döhner classification).[1]
CIRS=cumulative illness rating scale; CLL=chronic lymphocytic leukaemia; CO=chlorambucil + obinutuzumab; CrCl=creatinine clearance; ECOG=Eastern Cooperative Oncology Group; IGHV=immunoglobulin heavy-chain variable region; IQR=interquartile range; IRR=infusion-related reactions; MRD=minimal residual disease; O=obinutuzumab; ORR=overall response rate; OS=overall survival; PFS=progression-free survival; R/R=relapsed/refractory; SLL=small lymphocytic lymphoma; uIGHV=unmutated immunoglobulin heavy-chain variable region.
