TOPLINE: 

Acalabrutinib plus obinutuzumab demonstrated superior progression-free survival (PFS) and overall survival compared with chlorambucil-obinutuzumab in treatment-naive chronic lymphocytic leukemia (CLL), with a 42% lower risk for disease progression or death than acalabrutinib alone after a median follow-up of 74.5 months.

METHODOLOGY:

• A phase 3, randomized, open-label trial enrolled 535 patients who were randomly assigned 1:1:1 to receive acalabrutinib-obinutuzumab (n = 179), acalabrutinib monotherapy (n = 179), or chlorambucil-obinutuzumab (n = 177).
• Participants aged ≥ 65 years or 18-65 years with comorbidities were included if they had treatment-naive CD20+ CLL requiring treatment, per the International Workshop on CLL 2008 criteria.
• Analysis included a median follow-up of 74.5 months, with PFS as the primary endpoint for the acalabrutinib-obinutuzumab vs chlorambucil-obinutuzumab comparison.
• Treatment involved acalabrutinib 100 mg twice daily continuously, with obinutuzumab 1000 mg administered on days 1/2, 8, and 15 of cycle 2 and day 1 of cycle 3 in the combination arm.

TAKEAWAY:

• Median PFS was not reached for acalabrutinib-obinutuzumab and acalabrutinib monotherapy vs 27.8 months for chlorambucil-obinutuzumab (both P < .0001), with estimated 72-month PFS rates of 78.0%, 61.5%, and 17.2%, respectively.
• Acalabrutinib-obinutuzumab demonstrated improved overall survival vs chlorambucil-obinutuzumab (hazard ratio [HR], 0.62; P = .0349), with 72-month overall survival rates of 83.9%, 75.5%, and 74.7% for the acalabrutinib-obinutuzumab, acalabrutinib, and chlorambucil-obinutuzumab arms.
• Post hoc analysis showed acalabrutinib-obinutuzumab reduced risk for disease progression or death by 42% compared with acalabrutinib monotherapy (HR, 0.58; P = .0229).
• Rates of adverse events were similar between acalabrutinib-containing arms and consistent with known safety profiles of both drugs.

IN PRACTICE:

“With longer follow-up, ELEVATE-TN demonstrated for the first time that patients with CLL that obtain CRs [complete responses] have significantly longer PFS with either acalabrutinib monotherapy or acalabrutinib-obinutuzumab treatment. In post hoc analyses assessing the benefit of adding obinutuzumab to acalabrutinib, patients treated with acalabrutinib-obinutuzumab had significantly higher ORR (overall response rate; 96% vs 90%; P = .0220) and CR rates (37% vs 19%; P = .0220) than acalabrutinib monotherapy,” wrote the authors of the study.

SOURCE:

This study was led by Jeff Sharman, MD, Willamette Valley Cancer Institute and Research Center in Eugene, Oregon. It was published online in Blood.

LIMITATIONS:

According to the authors, the study design was not powered to detect statistical differences between the acalabrutinib-containing arms. Additionally, the influence of geriatric function on treatment outcomes was not assessed, though age and Eastern Cooperative Oncology Group performance status were predictors of worse outcomes in multivariate analysis. The study follow-up period coincided with the COVID pandemic, which may have affected overall study conduct, including missed patient assessment visits.

DISCLOSURES:

This study was funded by AstraZeneca Group. Sharman reported having relationships with AbbVie, AstraZeneca, BeiGene, Lilly, Newave, Merck, Genentech, TG Therapeutics, Genmab, and Regeneron. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.