Study design
The ALLIANCE study was a randomised, phase III study comparing the treatment regimens bendamustine and rituximab (BR), IMBRUVICA® and rituximab (IMBRUVICA® + R) and IMBRUVICA® alone in firstline CLL patients ≥65 years old.
Median age
BR cohort
70 years
(65-86)
IMBRUVICA® + R
71 years
(65-86)
IMBRUVICA® cohort
71 years
(65-89)
Key patient eligibility criteria:
- Treatment-naïve CLL requiring therapy
- ≥65 years
- ECOG PS 0-2
- Not receiving active systemic anticoagulation treatment
The ALLIANCE study included patients with high-risk features
High-risk features included TP53 mutation, del(11q), del(17p) and/or unmutated IGHV
Baseline characteristics
| All patients | BR | IMBRUVICA® | IMBRUVICA® + R |
|
Median age (range), years | 71 (65–89) | 70 (65–86) | 71 (65–89) | 71 (65–86) | 0.53 |
Male, n (%) | 367 (67) | 119 (65) | 123 (68) | 125 (69) | 0.75 |
High-risk disease according to modified Rai stage, n (%) | 296 (54) | 99 (54) | 99 (54) | 98 (54) | 0.99 |
| ECOG performance status, n (%)† 0 1 2 | 271 (50) 259 (47) 17 (3) | 98 (54) 75 (41) 10 (5) | 87 (48) 90 (49) 5 (3) | 86 (47) 94 (52) 2 (1) | 0.06 |
FISH analysis according to hierarchical classification of Döhner et al. - n/total n (%)‡ |
|
| 9/181 (5) 35/181 (19) 40/181 (22) 32/181 (18) 65/181 (36) | 11/180 (6) 37/180 (21) 38/180 (21) 29/180 (16) 65/180 (36) | 0.99 |
Mutated TP53, n/N (%) | 51/510 (10) | 16/174 (9) | 15/168 (9) | 20/168 (12) | 0.60 |
Complex karyotype, n/N (%)§ | 143/499 (29) | 44/166 (27) | 39/165 (24) | 60/168 (36) | 0.04 |
Unmethylated ZAP70, n/N (%) | 287/546 (53) | 95/182 (52) | 96/182 (53) | 96/182 (53) | 0.99 |
Unmutated IGHV gene, n/N (%) | 218/360 (61) | 71/123 (58) | 77/122 (63) | 70/115 (61) | 0.69 |
6 x 28-day cycles of:
Bendamustine
90 mg/m2 on Days 1 and 2 of each cycle
Rituximab
325 mg/m² on day prior to Day 1 of cycle 1
500 mg/m² on Day 1 of cycles 2-6
(n=183)
IMBRUVICA®:
IMBRUVICA®
420 mg once daily
until disease progression or unacceptable toxicity
(n=182)
6 x 28-day cycles of:
Rituximab
325 mg/m² on Day 1 of cycle 2-6
(n=182)
and
IMBRUVICA®
420 mg once daily
until disease progression or unacceptable toxicity
.png?width=1300&height=256&format=webp&quality=50 "1:1:1 Randomised")
Patients in the BR cohort who had disease progression could cross over to receive IMBRUVICA® within 1 year after progression.
Primary endpoint
PFS
Secondary endpoint
OS
38.0 months extended median follow-up
CLL patient subgroups
uIGHV patients
Genetic aberration patients
Fit patients
Relapsed / refractory patients
Back to IMBRUVICA® studies
*All P values are for comparisons across all three treatment groups and are two-sided. P values for continuous variables were calculated with the use of the Kruskal–Wallis test, and P values for categorical variables were calculated with the use of the chi-square test or Fisher's exact test.
†ECOG performance-status scores range from 0 to 5, with higher scores indicating greater disability.
‡Central FISH analysis was performed with the use of the hierarchical classification method established by Döhner et al.
§Complex karyotype was defined as the presence of at least three unrelated abnormalities as assessed by central review.
BR=bendamustine + rituximab; CLL=chronic lymphocytic leukaemia; ECOG PS=Eastern Cooperative Oncology Group Performance Status; FISH=fluorescence in situ hybridisation; IGHV=immunoglobulin heavy-chain variable region; OS=overall survival; PFS=progression-free survival; R=rituximab; R/R=relapsed/refractory; SLL=small lymphocytic lymphoma; uIGHV=unmutated Iimmunoglobulin heavy-chain variable region.
