Real-World Comparison of Time to Next Treatment for Patients with CLL Initiated on First-Line Treatment with Ibrutinib Versus Acalabrutinib

Introduction: Treatment guidelines recommend Bruton's tyrosine kinase inhibitors (BTKi) ibrutinib (once-daily) and acalabrutinib (twice-daily) as preferred regimens for chronic lymphocytic leukemia (CLL); however, there are no studies comparing the effectiveness of ibrutinib and acalabrutinib as first-line (1L) therapy in CLL. This study investigated time to next treatment (TTNT) for patients with CLL initiated on 1L ibrutinib or acalabrutinib in real-world (RW) clinical practice in the US.

Methods: Specialty pharmacy electronic medical records from academic integrated care networks (11/21/2018-4/30/2022) were used to identify adults with CLL who initiated ibrutinib or acalabrutinib in 1L (index date) on or after the date of acalabrutinib approval for CLL (11/21/2019). A washout period of ≥12 months without antineoplastic agent use pre-index was required to confirm use as 1L therapy. Patients were excluded if there was concomitant use of another antineoplastic agent during the first 28 days post-index.

Characteristics evaluated in the 12-month baseline period were compared between ibrutinib and acalabrutinib cohorts using t-tests for continuous variables and chi-square tests for categorical variables. TTNT was defined as the time from the index date to the initiation a next or additional treatment. Patients without a next/additional treatment were censored at death or end of data (4/30/2022). Patients with a within-class BTKi switch at any time post-index were censored at time of switch, as this may have indicated a switch due to tolerability rather than progression. Patients who added an anti-CD20 antibody or venetoclax to the BTKi within 180 days post-index were censored at time of add-on, as these may not have indicated overt disease progression but rather late initiation of a second anti-cancer agent as a 1L combination treatment strategy. Beyond 180 days, anti-CD20 or venetoclax add-ons were considered as a next/additional treatment. TTNT was described using Kaplan Meier curves and compared between ibrutinib and acalabrutinib using a Cox proportional hazards model adjusted for the following baseline variables: age, gender, region, race, year of index date, Quan-Charlson Comorbidity Index (Quan-CCI), chronic pulmonary disease (CPD), peripheral vascular disease, hypertension, atrial fibrillation (AF), metastatic cancer, use of corticosteroids, and use of antiplatelets.

Results: Among 710 and 373 patients in the ibrutinib and acalabrutinib cohorts, respectively, mean age was 71.5 and 72.4 years (P=0.159) and 38.5% and 38.3% were female (P=0.971; Table). Mean baseline Quan-CCI score was similar for ibrutinib and acalabrutinib (3.1 vs 3.0; P=0.597); a higher proportion of patients in the ibrutinib cohort had CPD (13.6% vs 8.8%; P=0.024), peripheral vascular disease (7.8% vs 4.1%; P=0.022), and hypertension (41.4% vs 32.2%; P=0.003) at baseline, while AF was similar (7.0% vs 9.9%, P=0.098). Baseline corticosteroid use was lower in the ibrutinib cohort (14.5% vs 20.1%; P=0.018), but antiplatelet use was higher (7.0% vs 3.5%; P=0.017).

Mean (median [range]) follow-up was 17.1 (18.1 [1.0-29.3]) months for the ibrutinib cohort and 12.5 (11.9 [1.0-29.1]) months for the acalabrutinib cohort. Four/710 (0.6%) patients in the ibrutinib cohort and 16/373 (4.3%) in the acalabrutinib cohort added an anti-CD20 antibody to the BTKi within 180 days and were censored at that point. Ten/710 (1.4%) and 8/373 (2.1%) patients added venetoclax to ibrutinib or acalabrutinib within 180 days and were censored at that point. The proportion of patients in the ibrutinib cohort who initiated a next or additional treatment was 5.9% relative to 7.5% for acalabrutinib. After adjusting for baseline characteristics, patients treated with acalabrutinib were 89% more likely to start a next or additional treatment than those treated with ibrutinib (hazard ratio = 1.89 [95% confidence interval] = [1.12, 3.13]; P=0.016; Figure). Results were similar when censoring anti-CD20 add-ons at any time (hazard ratio = 1.82 [95% confidence interval] = [1.08, 3.03]; P=0.025).

Conclusions: In this large US RW study, patients with CLL treated with 1L acalabrutinib were significantly more likely to start a next treatment or add/intensify therapy than those treated with 1L ibrutinib. RW treatment patterns also suggest a higher propensity to add an anti-CD20 antibody to acalabrutinib versus ibrutinib in 1L CLL.

Jacobs:AbbVie: Consultancy, Speakers Bureau; AstraZeneca: Consultancy, Speakers Bureau; TG Therapeutics: Research Funding; Verastem: Consultancy; Pharmacyclics, an AbbAvie Company: Consultancy, Research Funding, Speakers Bureau; Beigene: Speakers Bureau; Teneobio: Research Funding; Janssen: Speakers Bureau; MEI Pharma: Research Funding. Lu:Janssen Scientific Affairs, LLC: Current Employment, Current equity holder in publicly-traded company. Emond:Analysis Group, Inc.: Other: BE is an employee of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study. Morrison:Analysis Group, Inc.: Other: LM is an employee of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study. Kinkead:Analysis Group, Inc.: Other: FK is an employee of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study. Lefebvre:Analysis Group, Inc.: Other: PL is an employee of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study. Lafeuille:Analysis Group, Inc.: Other: MHL is an employee of Analysis Group, Inc., a consulting company that has provided paid consulting services to Janssen Scientific Affairs, LLC, which funded the development and conduct of this study. Khan:Janssen Scientific Affairs, LLC: Current Employment, Current equity holder in publicly-traded company. Wu:Janssen Scientific Affairs, LLC: Current Employment, Current equity holder in publicly-traded company, Patents & Royalties. Qureshi:Janssen Scientific Affairs, LLC: Current Employment; Merck: Ended employment in the past 24 months. Levy:Morphosys: Honoraria, Speakers Bureau; BeiGene: Honoraria, Speakers Bureau; Seagen: Honoraria, Speakers Bureau; Takeda: Honoraria, Speakers Bureau; Karyopharm: Honoraria, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; GSK: Honoraria, Speakers Bureau; Epizyme: Honoraria, Speakers Bureau; TG Therapeutics: Honoraria, Speakers Bureau; Baylor University Medical Center: Current Employment; AstraZeneca: Honoraria, Speakers Bureau; BMS: Honoraria, Speakers Bureau; Amgen: Honoraria, Speakers Bureau; Abbvie: Honoraria, Speakers Bureau; Dova: Honoraria, Speakers Bureau; Jazz Pharmaceuticals: Honoraria, Speakers Bureau; Sellas: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Speakers Bureau; Gilead: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau.