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.[1]
Median age[1]
BR cohort
70 years
(65-86)
IMBRUVICA® + R
71 years
(65-86)
IMBRUVICA® cohort
71 years
(65-89)
Key patient eligibility criteria:[1][2]
- 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[1]
High-risk features included TP53 mutation, del(11q), del(17p) and/or unmutated IGHV
Baseline characteristics[1]
| 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)[1]
IMBRUVICA®:
IMBRUVICA®
420 mg once daily
until disease progression or unacceptable toxicity
(n=182)[1]
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[1]
.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.[1]
Primary endpoint[1]
PFS
Secondary endpoint[1]
OS
38.0 months extended median follow-up[1]
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.[1]
†ECOG performance-status scores range from 0 to 5, with higher scores indicating greater disability.[1]
‡Central FISH analysis was performed with the use of the hierarchical classification method established by Döhner et al.[1]
§Complex karyotype was defined as the presence of at least three unrelated abnormalities as assessed by central review.[1]
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.
