Results support long-term use of CALQUENCE for R/R CLL, including
patient subgroups with high-risk features.5
Favourable efficacy over SOC regimens
at ~4 years of follow-up5
Median PFS was not reached and was
significantly prolonged with CALQUENCE
vs IdR/BR, regardless of genomic features1,5
Lower rates of discontinuation due to
AEs vs IdR/BR (no statistical
significance reported)1
ASCEND study was a pivotal, Phase 3, open-label, randomised, multicentre trial to determine how CALQUENCE performed compared with existing treatments, in patients with relapsed/refractory CLL – the first to compare CALQUENCE to a small molecule agent in R/R CLL1
After confirmed disease progression, crossover was allowed from the IdR or BR arm to the CALQUENCE arm.1 The trial met its primary endpoint at the data cut-off (15 January 2019) for the interim analysis.1
*Patients were randomised 1:1 to receive either CALQUENCE 100 mg twice daily until disease progression or unacceptable toxicity1
OR investigator’s choice of:
• Idelalisib (150 mg twice daily) administered orally until disease progression or unacceptable toxicity in combination with rituximab (375 mg/m2 IV on Day 1 of the first cycle, followed by 500 mg/m2 IV every 2 weeks for 4 doses and then every 4 weeks for 3 doses, for a total of 8 infusions)1
• Bendamustine 70 mg/m2 IV on Days 1 and 2 of each 28-day cycle in combination with rituximab (375 mg/m2 IV on Day 1 of the first cycle and 500 mg/m2 IV thereafter on Day 1 of Cycles 2 through 6).1
Key inclusion and exclusion criteria*1
Key inclusion criteria:1
- Age ≥18 years
- Received ≥1 prior systemic therapy for CLL
- Estimated CrCL ≥30 mL/min†
- ECOG PS ≤2
- Adequate haematologic, hepatic, and renal function
Key exclusion criteria:1
- Prior exposure to:
- BCL-2 inhibitors (e.g., venetoclax)
- BTK inhibitors (e.g., ibrutinib)
- PI3K inhibitors (e.g., idelalisib)
- Patients who had previously received bendamustine treatment were allowed to receive bendamustine provided the duration of the prior response lasted >24 months
- Required or was receiving anticoagulation with warfarin or equivalent vitamin K antagonists (e.g., phenprocoumon) within 7 days of first dose of the study drug
- Significant cardiovascular disease
- Exception: Patients with controlled, asymptomatic atrial fibrillation were not excluded
*Not all inclusion/exclusion criteria have been included. For full details, please refer to the reference.1
†Calculated by use of the Cockcroft-Gault equation.
CALQUENCE was studied in a broad range of patients reflecting clinical practice
Patient characteristics were well balanced between treatment arms1
*Anti-CD5a antibody, n=6; anti-CD19 antibody, n=3; immunomodulatory agent, n=2; anti-PD-L1 antibody,
n=1; anti-CD23 antibody, n=1; autologous dendritic cell vaccine, n=1; hydroxycarbamide, n=1.1
CALQUENCE significantly extended IRC-assessed PFS vs investigator's choice (IdR or BR)1,2
PRIMARY ENDPOINT: Median PFS significantly longer with CALQUENCE: NR for
CALQUENCE vs 16.5 months (95% CI: 14.0 – 17.1) with IdR or BR.1
IRC-assessed PFS after a median follow-up of 16.1 months1,2
At the time of primary analysis, the number of events (disease progression or death) in each arm was 27 (17%) for CALQUENCE and 68 (44%) for IdR or BR.2
Investigator-assessed PFS for CALQUENCE vs both IdR and BR at longer-term follow-up5
(median follow-up: Calquence 46.5 months; IdR/BR 45.3 months)
ASCEND was the first trial to compare a BTKi with a small molecule agent in R/R CLL1–5
PFS rates were based on the iwCLL 2008 criteria in patients with R/R CLL.2
Patients were censored at the time when any subsequent anticancer therapies were received.
*Hazard ratios were based on unstratified Cox proportional hazards model.
†P value was based on stratified log-rank test.
At long-term follow-up, PFS was generally consistent across prespecified patient subgroups, including those with high-risk genomic features5
Investigator-assessed OS and ORR with CALQUENCE and IdR/BR5 (median follow-up: Calquence 46.5 months; IdR/BR 45.3 months)
Most common AEs (≥10%) from the ASCEND study1
- Most frequently reported AEs in patents receiving CALQUENCE included infection (57%) and bleeding (26%)*1
- In patients receiving CALQUENCE, common grade 3/4 AEs included neutropenia (16%), infection (15%), and anaemia (12%)†1
Adapted from Ghia P. et. al. 2020.
Median follow-up time: 16.1 months; median duration of exposure: acalabrutinib 15.7 months; idelalisib in IdR 11.5 months
Incidence of ARs ■≥10% ■<10% - ≥1% ■<1%
*Most common forms of bleeding were contusion and haematoma.1
†Most common forms of infection (grades 1-4) were upper respiratory tract infection, pneumonia, and respiratory tract infection.1
‡One patient in the CALQUENCE arm did not receive study treatment.1
Dose reductions and discontinuations with CALQUENCE vs IdR or BR1
Adapted from Ghia P, et al. 2020.
Median follow-up time: 16.1 months
*Among treatment-emergent adverse events leading to treatment discontinuation, one patient discontinued CALQUENCE monotherapy due to headache.
There were no reports of atrial fibrillation leading to CALQUENCE discontinuation in any of the treatment arms.1
No dose reductions were allowed for rituximab in ASCEND.1
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Abbreviations:
AE, adverse event; ALT, alanine transaminase; AR, adverse reaction; AST, aspartate aminotransferase; BCL-2, B-cell lymphoma 2; BR, bendamustine plus rituximab; BTKi, Bruton tyrosine kinase inhibitor; CI, confidence interval; CLL, chronic lymphocytic leukaemia; CrCL, creatinine clearance; del(17p), deletion of 17p; ECOG PS, Eastern Cooperative Oncology Group Performance Status; FISH, fluorescence in situ hybridisation; HR, hazard ratio; IdR, idelalisib plus rituximab; IGHV, immunoglobulin heavy chain variable region; IQR, interquartile range; IRC, independent review committee; IV, intravenous; iwCLL, International Workshop on Chronic Lymphocytic Leukemia; LTFU, long-term follow-up; mo, month; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PI3K, phosphoinositide 3-kinase; R/R, relapsed/refractory; SOC, standard of care; SYK, spleen-associated tyrosine kinase; TP53, tumour protein 53.
References:
1. Ghia P, et al. J Clin Oncol. 2020;38(25):2849–2861. 2. Calquence Summary of Product Characteristics. 3. Ibrutinib 560 mg Film-Coated Tablets SmPC. 4. Zanabrutinib 80 mg hard capsules SmPC. 5. Ghia P, et al. ASCEND study long-term follow-up. Poster P668. Presented at European Hematology Association (EHA) Annual Meeting; June 9-12, 2022, Vienna, Austria.
Adverse events should be reported
Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to AstraZeneca by visiting contactazmedical.astrazeneca.com or by calling 0800 783 0033.
May 2025 I GB-62248