Comparing Fixed-Duration vs Continuous Treatment for CLL

This article explains results from the CLL17 trial, a German study that evaluated whether a time-limited treatment can work as well as ongoing treatment for people with newly diagnosed CLL. Read the results and how they may affect treatment choices. 

Why treatment length matters in CLL

CLL can often be managed for many years. Today, there are two main ways targeted treatments are used:

• Continuous-duration treatment, where a medicine is taken every day until it stops working or side effects become unmanageable.
• Fixed-duration treatment, where medicines are taken for a set amount of time, usually about one year, and then stopped.

Until now, these two approaches had not been directly compared in a large study. The CLL17 trial was designed to answer that question.

How the CLL17 study was designed

The CLL17 trial was a phase 3 study that enrolled 909 people with previously untreated CLL. Participants were randomly assigned to one of three treatment groups:

• Continuous ibrutinib (Imbruvica, Pharmacyclics/Johnson & Johnson) alone
• Fixed-duration venetoclax (Venclexta, AbbVie) plus obinutuzumab (Gazyva, Genentech) for one year
• Fixed-duration venetoclax plus ibrutinib for a little over a year 

Researchers followed participants for a median of three years to see how long treatment continued to work and how people tolerated therapy.

The main outcome measured was progression-free survival, which means the length of time people lived without their CLL progressing. 

What the study found after three years

At three years, the percentage of patients who were alive without CLL progressing was similar across all groups:

• 81.1% of patients who took venetoclax plus obinutuzumab
• 81.0% on continuous ibrutinib
• 79.4% on venetoclax plus ibrutinib

These results showed that both fixed-duration options worked just as well as continuous treatment. This is important because it means people may be able to stop treatment without giving up effectiveness.

Overall survival, meaning how many people were alive at three years, was also high and similar across all groups.

Deeper responses with fixed-duration treatment

One of the biggest differences between treatments was how deeply they reduced CLL.

Researchers measured undetectable minimal residual disease, or uMRD. This means little to no CLL cells were found using very sensitive tests.

• 73.3% of people who received venetoclax plus obinutuzumab reached uMRD
• 47.2% on venetoclax plus ibrutinib reached uMRD
• 0% on continuous ibrutinib reached uMRD

For patients, deeper responses like uMRD may be linked to longer treatment-free periods. 

How genetics affected outcomes

The study also looked at results based on common risk factors, such as IGHV status and TP53 changes.

• For people with unmutated IGHV, outcomes were similar across all treatments.
• For people with del(17p)/TP53 mutation, at 3 years after the start of treatment, the percentage of patients who were alive without CLL progressing was 62.0% those who took venetoclax plus obinutuzumab, 69.0% on venetoclax plus ibrutinib, and 79.4% on continuous ibrutinib. 

This highlights why genetic testing remains important before starting treatment.

Side effects differed between treatments

Side effects were seen across all groups, but the types varied:

• Infections and stomach-related symptoms were frequent in all groups.
• Heart-related side effects were more common with continuous ibrutinib.
• Secondary cancers were reported more often with continuous treatment, affecting 18.5% of patients, than with fixed-duration options, at 11.5% of patients. 

Understanding these differences can help patients and care teams weigh benefits and risks based on personal health history. 

What this means for people with newly diagnosed CLL

The CLL17 trial directly compared continuous and fixed-duration targeted therapies in CLL. The results suggest that time-limited treatment can be just as effective as staying on therapy indefinitely.

For many people, this opens the door to treatment plans that include planned breaks, fewer long-term side effects, and more flexibility.

Talk with your CLL specialist about how these findings may apply to your specific type of CLL and personal goals.

To learn more about CLL therapies, view our CLL Therapy Guide. 

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Source: 

• Fixed-duration versus continuous targeted treatment for previously untreated chronic lymphocytic leukemia: Results from the randomized CLL17 trial