Study design
The RESONATE-2 study was an open-label, multicentre, international, randomised phase III study to establish the long-term safety and efficacy of firstline IMBRUVICA® vs. chlorambucil treatment in patients with CLL/SLL, with up to 7 years of follow-up.[1][2]
Median age[1]
IMBRUVICA® cohort
73 years
(65-89)
Chlorambucil cohort
72 years
(65-90)
Key patient eligibility criteria:[1]
- Treatment-naïve CLL/SLL requiring therapy
- ≥65 years
- Comorbidity that may preclude FCR for older patients
- Del(17p) exclusion
The RESONATE-2 study included patients with high-risk features[1]
High-risk features included TP53 mutation, del(11q), and/or uIGHV
Baseline characteristics[1]
Characteristic | IMBRUVICA® | Chlorambucil |
| Median age (range), years ≥70 years, n (%) | 73 (65–89) 96 (71) | 72 (65–90) 93 (70) |
Male, n (%) | 88 (65) | 81 (61) |
| ECOG performance status, n (%) 0 1–2 | 60 (44) 76 (56) | 54 (41) 79 (59) |
Rai stage III or IV, n (%) | 60 (44) | 62 (47) |
CIRS score >6, n (%) | 42 (31) | 44 (33) |
Creatinine clearance <60 mL/min, n (%) | 60 (44) | 67 (50) |
Bulky disease ≥5 cm, n (%) | 54 (40) | 40 (30) |
β-2 microglobulin level >3.5 mg/L, n (%) | 85 (63) | 89 (67) |
Haemoglobin ≤11 g/dL, n (%) | 51 (38) | 55 (41) |
Platelet count ≤100 x 109/L, n (%) | 35 (26) | 28 (21) |
del(11q), n/N (%) | 29/130 (22) | 25/121 (21) |
Unmutated IGHV, n/N (%) | 58/101 (57) | 60/103 (58) |
TP53 mutation n/N (%) | 12/124 (10) | 3/94 (3) |
High prognostic risk features, * n (%) | 74 (54) | 69 (52) |
IMBRUVICA®
420 mg once daily
until disease progression or unacceptable toxicity
(n=136)[1]
.png?width=1280&height=720&format=webp&quality=50 "Randomised 1:1")
Chlorambucil
0.5–0.8 mg/kg
Days 1 + 15 of 28-day cycle, up to 12 cycles
(n=133)[1]
Primary endpoint[1]
PFS
Secondary endpoint[1]
ORR and OS
84.0 months
extended median follow-up[2]
CLL patient subgroups
uIGHV patients
Genetic aberration patients
Fit patients
Relapsed / refractory patients
Back to IMBRUVICA® studies
*TP53 mutation, del(11q), and/or unmutated IGHV.[^1]
CIRS=cumulative illness rating scale; CLL=chronic lymphocytic leukaemia; ECOG=Eastern Cooperative Oncology Group; IGHV=immunoglobulin heavy-chain variable region; 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.
