Fixed-Duration Venetoclax Plus Obinutuzumab for CLL

Authored by Ann Liu, PhD
Medically Reviewed by Ed Ratner, MD

The Bottom Line:

With ten years of follow-up, the CLL14 study established that one year of treatment with venetoclax plus obinutuzumab produces long remissions in patients with treatment-naïve CLL.

Who Performed the Research and Where Was it Presented:

Dr. Kirsten Fischer from University Hospital of Cologne and colleagues presented the results at the European Hematology Association (EHA) Annual Meeting in 2026.

Background:

The CLL14 study was one of the first studies to establish that fixed-duration targeted therapy could be used to treat chronic lymphocytic leukemia (CLL) / small lymphocytic lymphoma (SLL). The study began recruiting patients with treatment-naïve CLL in 2015, testing the combination of venetoclax and obinutuzumab given for one year against chemoimmunotherapy, which was the standard of care at the time. Now, after a decade of follow-up, researchers reported the final results of the CLL14 trial.

Methods and Participants:

The CLL14 study included 432 patients with previously untreated CLL / SLL and randomly assigned them to receive either:

1. Venetoclax plus obinutuzumab for one year
2. Chlorambucil plus obinutuzumab

All patients were followed for eight years or more after the end of treatment. The primary outcome was progression-free survival (how long before a patient’s disease got worse).

Results:

• Half of patients were followed for 10 years or more.
• The median progression-free survival was six years with venetoclax-obinutuzumab and three years with chemoimmunotherapy.
• Median time to next treatment was eight years with venetoclax-obinutuzumab and four years with chemoimmunotherapy.
• Patients with mutated IGHV had a median progression-free survival of nearly 10 years, but patients with unmutated IGHV (a higher-risk mutation) had a median progression-free survival of five years. and.
• Patients with TP53 mutations (another high-risk mutation) had a median progression-free survival of four years.
• After 10 years, more than half of the patients in the venetoclax-obinutuzumab group were still alive.
• Among those treated with venetoclax-obinutuzumab, 14/78 (18%)  of deaths were attributable to progression of CLL.
• Secondary cancer occurred in 19% with venetoclax-obinutuzumab and 11% in chemoimmunotherapy.

Conclusions:

The CLL14 study now has 10 years of follow-up, and it shows that fixed-duration venetoclax plus obinutuzumab produces long remissions in patients with previously untreated CLL. One year of therapy with venetoclax plus obinutuzumab produced remissions longer than six years in half of patients. It was also effective, but not for as long, in patients with high-risk genetic features such as unmutated IGHV and TP53 mutation. This study was instrumental in establishing fixed-duration targeted therapy as a standard option for the treatment of CLL / SLL.

Limited duration multi-drug treatment protocols have pros and cons compared to continuous use of a BTKi, but this study demonstrates one such combination is especially effective over at least 10 years for patients with mutated IGHV.  , Research continues on other combinations of both approved and experimental drugs that are more convenient, have fewer side effects, and enhance lengths of remission.  Patients with CLL / SLL now have multiple excellent choices between limited-duration and continuous targeted therapies that all can offer durable disease control and a low risk of dying due to lack of an effective treatment.

Links and Resources:

Watch the interview here:

You can read the actual EHA abstract here: Venetoclax-Obinutuzumab for Previously Untreated Chronic Lymphocytic Leukemia: Final Results of the Randomized CLL14 Study

Take care of yourself first.

Ann Liu, PhD