For eligible relapsed/refractory (R/R) CLL patients, CALQUENCE was generally well tolerated and showed next-generation BTK inhibition.
Non-inferior efficacy for
CALQUENCE vs ibrutinib, with a median PFS
of 38.4 months for both treatment groups
(median follow-up 40.9 months)1
Fewer incidences of any-grade
atrial fibrillation/flutter AEs
with CALQUENCE vs ibrutinib
(9.4% vs 16.0%; p=0.02)1
Numerically lower rates of
discontinuation due to AEs vs ibrutinib
(14.7% vs 21.3% respectively); no
statistical significance reported1
ELEVATE-RR was the first head-to-head study comparing first- and
second-generation BTKis1
A Phase 3, open-label, non-inferiority study of CALQUENCE vs ibrutinib in patients with
previously treated CLL and high-risk prognostic factors1
Acalabrutinib SmPC Posology: The recommended dose is 100 mg acalabrutinib twice daily (equivalent to a total daily dose of 200 mg).2
Refer to ibrutinib SmPC for recommended ibrutinib dosing information.3
*Dose modifications were allowed for adverse event management. Crossover between treatment groups was not permitted.1
†Efficacy analyses were performed for ITT population (all randomly assigned patients). Safety analyses, including the safety secondary endpoints, were performed for the safety population (all patients who received at least one dose of the study drug).1
‡The primary analysis was conducted after completion of enrolment and accrual of approximately 250 IRC-assessed PFS events.1
Key inclusion and exclusion criteria*1
Key inclusion and exclusion criteria*1
- Age ≥18 years
- Previously treated CLL requiring therapy as per iwCLL 2008 criteria
- Presence of del(17)(p13.1) and/or del(11)(q22.3) confirmed by central laboratory testing
- ECOG PS ≤2
Key exclusion criteria:1
- Significant cardiovascular disease† within 6 months of screening
- History of stroke or ICH within 6 months before randomisation
- Concomitant warfarin or equivalent vitamin K antagonist treatment
- Prior BTK or BCL-2 inhibitor treatment
- Requiring treatment with proton-pump inhibitors (CALQUENCE capsule formulation restricted use with PPIs; no longer applicable with tablet formulation)
*Not all inclusion/exclusion criteria have been included. For full details, please refer to the reference.1
†Uncontrolled or symptomatic arrhythmias, congestive heart failure, or myocardial infarction.1
Baseline demographics and disease characteristics were well balanced
between the two treatment arms1
Adapted from Byrd JC, et al. 2021.
Data are n (%) unless otherwise specified.
*Patients with ≥3 chromosomal abnormalities and ≥1 structural abnormalities.
†A patient was only counted once for each category.
‡Includes doxorubicin, bleomycin, vinca alkaloids, etoposide, and platinum-based regimens.
CALQUENCE was the first second-generation BTKi to demonstrate non-inferiority to ibrutinib in IRC-assessed PFS*†1
Median follow-up 40.9 months; PFS 38.4 months in both treatment arms for the total population (comprising patients with 17p deletion and/or 11q deletion)‡1
Adapted from Byrd JC, et al. 2021.
*Defined as time from random assignment until disease progression or death from any cause.1
†At the data cut-off for the final analysis, 124 (46.3%) acalabrutinib patients and 109 (41.1%) ibrutinib patients remained on treatment.1
‡Three patients in the ibrutinib arm were censored because of PD or death immediately after missing ≥2 consecutive visits, and 7 patients in the acalabrutinib arm and 8 patients in the ibrutinib arm were censored at random assignment because of no baseline assessment and/or no adequate postbaseline assessment.1
PFS was consistent across subgroups
IRC-assessed PFS was generally consistent across prespecified subgroups for both
CALQUENCE and ibrutinib.1
Median overall survival not reached in either treatment group1
Secondary endpoint: Median OS* was not reached in either treatment arm at a median
follow-up of 40.9 months†1
Data presented are descriptive in nature.
*Time from random assignment to any-cause death.1
†Overall survival (OS) data were censored at randomisation for patients who were lost to follow-up immediately after randomisation. For patients not known to have died, OS data were censored at the last known date that the patient was alive before the analysis cut-off date or before the patient was lost to follow-up or study exit.1
Cumulative incidence of selected AEs of clinical interest1
Cumulative incidences of any-grade atrial fibrillation/flutter, hypertension, bleeding, diarrhoea, and arthralgia events with CALQUENCE vs ibrutinib1
Any-grade hypertension
CALQUENCE (9.4%, n=266) vs ibrutinib (23%, n=263)1
Any-grade atrial fibrillation/flutter*
CALQUENCE (9.4%, n=266) vs ibrutinib (16%, n=263)*1
*Secondary endpoint. Includes events with the preferred terms of atrial fibrillation and atrial flutter (a patient was only counted once if they experienced both types of events). Atrial flutter was reported in 1 patient in the CALQUENCE arm and in 2 patients in the ibrutinib arm (1 of the 2 ibrutinib patients also had an atrial fibrillation event and was counted only once for the combined atrial fibrillation or flutter term).1
Fewer patients discontinued CALQUENCE vs ibrutinib1
Discontinuation due to adverse events was numerically lower with CALQUENCE
than with ibrutinib1
AEs leading to discontinuation1
AEs leading to dose interruption and dose reduction1
†Defined as missing dose for ≥7 consecutive days; a subject is counted once per reason.1
‡Defined as taking a lower dose level for ≥3 consecutive days.1
The demonstrated safety profile of CALQUENCE offers a generally well-tolerated option for CLL patients1,4
Most common adverse events of any grade or grade ≥3 occurring in patients in either treatment arm in ELEVATE-RR1
Descriptive two-sided p<0.05 without multiplicity adjustment.
Adapted from Byrd JC, et al. 2021.
The most common infections (grade ≥3) in at least 2% of patients in either arm were
pneumonia, sepsis, and urinary tract infection.1
Data are reported as No. (%)
*Descriptive two-sided P<0.05 on the basis of Barnard’s exact test without multiplicity adjustment for all-grade adverse events.1
†Descriptive two-sided P<0.05 on the basis of Barnard’s exact test without multiplicity adjustment for grade ≥3 adverse events.1
Fewer any-grade atrial fibrillation/flutter events with CALQUENCE vs ibrutinib 1
(Patients with severe cardiovascular disease were excluded from CALQUENCE clinical studies)
Summary of adverse events of clinical interest1
Adapted from Byrd JC, et al. 2021.
Data are reported as No. (%) unless otherwise specified.
*Includes events with the preferred terms of hypertension, blood pressure increased, and blood pressure systolic increased.1
†Includes events with the preferred terms of atrial fibrillation and atrial flutter.1
‡Includes events with the preferred terms of torsade de pointes, ventricular arrhythmia, ventricular extrasystoles, ventricular fibrillation, ventricular flutter, ventricular tachyarrhythmia, and ventricular tachycardia.1
§Two-sided P value for any-grade event comparisons is <0.05 without multiplicity adjustment.
||Defined as any haemorrhagic event that was serious, grade ≥3 in severity, or a central nervous system haemorrhage (any severity grade).1
¶Most common grade ≥3 infections were pneumonia (acalabrutinib, 9.4%; ibrutinib, 8.4%), sepsis (1.1% vs 2.7%), and urinary tract infection (0.8% vs 1.5%).1
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ASCEND study
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Abbreviations:
AE, adverse event; AR, adverse reaction; BCL-2, B-cell lymphoma 2; BID, two times a day; BTK, Bruton tyrosine kinase; CI, confidence interval; CLL, chronic lymphocytic leukaemia; del(17p), deletion of 17p; ECOG PS, Eastern Cooperative Oncology Group Performance Status; HR, hazard ratio; ICH, intracranial haemorrhage; IGHV, immunoglobulin heavy chain variable region; ILD, interstitial lung disease; IRC, independent review committee; ITT, intention to treat; iwCLL, International Workshop on Chronic Lymphocytic Leukemia; NMSC, non-melanoma skin cancer; OD, once daily; PD, progressive disease; PFS, progression-free survival; PO, per os (by mouth); R/R, relapsed/refractory; SmPC, Summary of Product Characteristics; SPM, second primary malignancy; TP53, tumour protein 53.
References:
1. Byrd JC, et al. J Clin Oncol. 2021;39(31):3441–3452. 2. Calquence Summary of Product Characteristics. 3. Ibrutinib 560 mg Film-Coated Tablets SmPC. 4. Rogers KA, et al. Haematologica. 2021;106(9):2364–2373.
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-62245
Atrial fibrillation/flutter (secondary endpoint)
Bleeding events (post hoc analysis)
Diarrhoea (post hoc analysis)
Arthralgia (post hoc analysis)
Hypertension (post hoc analysis)
