Study design
The HELIOS study was a randomised, double-blind, placebo-controlled phase III study comparing the treatment regimens IMBRUVICA®, bendamustine and rituximab (IMBRUVICA® + BR) with placebo, bendamustine and rituximab (placebo + BR) in firstline patients with R/R CLL/SLL.[1]
Median age[1]
IMBRUVICA® + BR cohort
64 years
(31-86)
Placebo + BR cohort
63 years
(36-83)
Median prior therapies[1]
IMBRUVICA® + BR cohort
2
(1-11)
Placebo + BR cohort
2
(1-9)
Key patient eligibility criteria:[1]
- R/R CLL/SLL diagnosis
- ≥1 prior therapy
- ECOG 0–1
- Measurable nodal disease by CT
- Del(17p) exclusion
The HELIOS study included patients with high-risk features[1]
High-risk features included del(11q), and/or uIGHV
Baseline characteristics[1]
Characteristic | IMBRUVICA® + BR | Placebo + BR |
Age (years), n (%) | 64 (31–86) | 63 (36–83) |
| Female, n (%) Male, n (%) | 96 (33) 193 (67) | 100 (35) 189 (65) |
| Diagnosis Chronic lymphocyctic leukaemia Small lymphocyctic lymphoma | 257 (89) 32 (11) | 257 (89) 32 (11) |
| ECOG performance status 0 1 | 125 (43) 164 (57) | 126 (44) 163 (56) |
Rai-stage* | 256 | 258 |
Binet stage* | 256 | 258 |
Bulky disease ≥5 cm, n (%) | 168 (58) | 156 (54) |
Del(11q) | 87 (30) | 65 (22) |
| IGHV status* Mutated Unmutated | 259 49 (19) 210 (81) | 260 52 (20) 208 (80) |
| ZAP70 expression* Raised Not raised | 271 204 (75) 67 (25) | 276 190 (69) 86 (31) |
Purine analogue refractory | 75 (26) | 74 (26) |
| Previous lines of therapies Mean (range) 1 previous line 2 previous lines ≥3 previous lines | 289 2 (1–11) 140 (48) 72 (25) 77 (27) | 288 2 (1–9) 138 (48) 78 (27) 72 (25) |
| Previous therapy Purine analogue Alkylating agent Anti-CD20 | 206 (71) 275 (95) 203 (70) | 209 (72) 275 (95) 200 (69) |
| Common regimes used Fludarabine, cyclophosphamide and rituximab | 120 (42) 92 (32) 10 (3) 16 (6) | 109 (38) 102 (35) 9 (3) 15 (5) |
Time from progression or relapse since last line of treatment to randomisation (months) | 2.9 (0–48) | 2.6 (0–73) |
Time from last treatment to randomisation (months) | 24.0 (0.7–154.8) | 20.9 (0.2–160.8) |
Data are median (range), n (%), or n, unless otherwise stated
6 x 28-day cycles of:
Bendamustine
70 mg/m2 on Days 2–3 in cycle 1
and Days 1–2 in cycles 2–6
Rituximab
375 mg/m2 on Day 1 of cycle 1
500 mg/m2 on Day 1 of cycles 2–6
(n=289)
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:
Placebo
until disease progression or unacceptable toxicity
Bendamustine
70 mg/m2 on Days 2–3 in cycle 1
and Days 1–2 in cycles 2–6
Rituximab
375 mg/m2 on Day 1 of cycle 1
500 mg/m2 on Day 1 of cycles 2–6
(n=289)[1]
Patients in the placebo + BR cohort who had IRC-confirmed disease progression were permitted to cross over to the IMBRUVICA® + BR.[1]
Primary endpoint[1]
PFS
Secondary endpoint[1]
OS, ORR, investigator assessed PFS, MRD, FACIT-fatigue, rate of sustained haemoglobin and platelet improvement
63.7 months extended median follow-up[2]
CLL patient subgroups
uIGHV patients
Genetic aberration patients
Fit patients
Relapsed / refractory patients
Back to IMBRUVICA® studies
*Staging criteria for patients with CLL only, using diagnosis at study entry; not all samples were evaluable for biomarker data.[1]
BR=bendamustine+rituximab; CLL=chronic lymphocytic leukaemia; CT=computed tomography; ECOG=Eastern Cooperative Oncology Group; FACIT=Functional Assessment of Chronic Illness Therapy; IGHV=immunoglobulin heavy-chain variable region; IRC=independent review committee; mAb=monoclonal antibody; MRD=minimal residual disease; 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.
