FDA approves first all-oral 14-month venetoclax-acalabrutinib regimen for untreated CLL

The U.S. Food and Drug Administration has approved venetoclax (VENCLEXTA) plus acalabrutinib (CALQUENCE) for adults with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma, AbbVie and AstraZeneca said in company statements dated Feb. 20, 2026. One outlet noted the approval as Feb. 19, 2026, a discrepancy in reported timing among sources.

The clearance is based on results from the phase III AMPLIFY trial (NCT05197192), which randomized patients 1:1:1 to acalabrutinib plus venetoclax (AV), AV plus obinutuzumab (AVO), or investigator choice chemoimmunotherapy with fludarabine, cyclophosphamide and rituximab (FCR) or bendamustine plus rituximab (BR). The primary endpoint compared investigator-assessed progression-free survival for AV versus chemoimmunotherapy in the intention-to-treat population; overall survival and undetectable minimal residual disease were listed as key secondary endpoints.

Companies highlighted a marked clinical benefit. AstraZeneca said, "CALQUENCE plus venetoclax demonstrated statistically significant and clinically meaningful improvement in progression-free survival vs. chemoimmunotherapy, with 77% of patients progression free at three years in AMPLIFY Phase III trial." OncologyNewsCentral and LymphomaHub reported that fixed-duration AV reduced the risk of disease progression or death by 35% versus chemoimmunotherapy, with a hazard ratio of 0.65 (95% confidence interval, 0.49–0.87; P = .0038). At a median follow-up of 42.6 months, median PFS was not estimable in the AV group (reported as "not estimable" or "not reached" with a 95% CI lower bound of 51.1 months) versus 47.6 months in the chemoimmunotherapy group (95% CI, 43.3 months to not estimable).

On overall survival, OncologyNewsCentral reported that at a median follow-up of 41.0 months there were 18 deaths (6%) in the AV group and 42 deaths (14%) in the chemoimmunotherapy group. AMPLIFY excluded patients with 17p deletion or TP53 mutation, limiting the label to patients without those high-risk genomic features.

Safety signals were described as consistent with known profiles of the two agents. LymphomaHub listed the most common serious adverse events in the AV arm as COVID-19 including COVID-19 pneumonia at 9%, secondary primary malignancies at 2.7%, and neutropenia at 2.1%.

Company leaders and clinicians framed the approval as a meaningful shift toward time-limited, oral therapy. Jennifer Brown, MD, PhD, principal investigator of AMPLIFY, said, "The continuous regimens frequently used to treat chronic lymphocytic leukemia often come with side effects that may become burdensome to patients over time. The US approval of the CALQUENCE combination offers patients an all‑oral, 14‑month, fixed‑duration treatment option that is highly effective and well‑tolerated, and gives physicians greater flexibility to tailor treatment plans for individual patient needs and goals." Dave Fredrickson, executive vice president at AstraZeneca, added, "Today’s approval delivers the first all‑oral, fixed‑duration BTK inhibitor‑based regimen in the US for the treatment of chronic lymphocytic leukemia. This CALQUENCE combination has the potential to meaningfully change 1st‑line chronic lymphocytic leukemia treatment decisions and underscores our commitment to improving on the current standard of care for people living with blood cancers." AbbVie emphasized the combination as "the first and only all‑oral, fixed‑duration regimen for previously untreated patients," and Svetlana Kobina of AbbVie called the approval "a significant milestone." Dr. Brian Koffman of CLL Society noted the value of an "all oral, time‑limited option" for patients.

Although the approval promises shorter, clinic-free treatment for many patients, key practical details remain unreported in company materials: total AMPLIFY enrollment, full toxicity grading and discontinuation rates, dosing schedules, official FDA label language, and cost and insurance coverage implications. Clinicians and patients will likely weigh the regimen's fixed 14-month course and oral delivery against access, affordability and applicability for patients with high-risk genomic features not studied in AMPLIFY.