Where chronic lymphocytic leukemia treatment is heading

About 21,000 people in the US are diagnosed with chronic lymphocytic leukemia each year, mostly older adults, and many need no treatment for years. When treatment is needed, chemotherapy has largely been replaced by targeted pills (BTK and BCL-2 inhibitors). The big shift now is from taking pills indefinitely to fixed-length or blood-test-guided treatment.

• 361studies open or running
• 41phase 3 trials
• 804papers published this year
• 40NIH-funded projects

1. Now

   Nov 2026

   A set treatment course works as well as lifelong pillsHappened 81.1% progression-free at 3 yrs

   Fixed-duration venetoclax combinations matched continuous ibrutinib: about 81% progression-free at 3 years.

   81.1%: progression-free at 3 years with fixed-duration venetoclax-obinutuzumab.

   • CLL17 trial

   Blood tests decide when to stopHappened 6.9% progressed or died

   MRD-guided ibrutinib-venetoclax: 6.9% progressed or died vs 22.4% with ibrutinib alone.

   6.9%: progressed or died with MRD-guided ibrutinib-venetoclax, vs 22.4% with ibrutinib alone.

   • FLAIR trial

   Chemo-free fixed treatment beats chemoHappened 83.1% progression-free at 3 yrs

   Acalabrutinib-venetoclax-obinutuzumab: 83.1% progression-free at 3 years vs 66.5% with chemo.

   83.1%: progression-free at 3 years with the three-drug regimen, vs 66.5% with chemo.

   • AMPLIFY trial

   A newer BTK pill approved first-lineHappened 80% lower risk

   Pirtobrutinib cut progression risk 80% vs chemo-immunotherapy; approved October 2026.

   80%: lower risk of progression or death than chemo-immunotherapy.

   • BRUIN CLL-313 trial

2. 6 months

   by May 2027

   Pirtobrutinib combination filingLikely

   BRUIN CLL-322 (pirtobrutinib plus venetoclax-rituximab) improved progression-free survival; a filing is planned.

   • BRUIN CLL-322

3. 12 months

   by Nov 2027

   Treating high-risk CLL before symptomsPossible

   A National Cancer Institute trial tests whether starting treatment early helps high-risk CLL; due October 2028.

   • Early treatment trial

4. 3 years

   by late 2029

   A drug that destroys the BTK proteinPossible

   BeOne's tacabrutideg, a BTK degrader, is compared with pirtobrutinib (500 people); due April 2028.

   • Tacabrutideg trial

   A next-generation BCL-2 pillPossible

   Sonrotoclax combinations are in two phase 3 trials against venetoclax-based standards; due 2029-2032.

   • Sonrotoclax plus zanubrutinib
   • Sonrotoclax plus obinutuzumab

5. 5 years

   by late 2031

   Another reversible BTK pillLong shot

   Merck's nemtabrutinib (1,200 people) is compared with ibrutinib or acalabrutinib; due 2032.

   • Nemtabrutinib trial

The research paths

Open to join now

• Relapsed after BTK inhibitor

  Tacabrutideg vs pirtobrutinib

  Phase 3 · 217 sites

  Locations and eligibility →

• Untreated CLL

  Sonrotoclax plus obinutuzumab

  Phase 3 · 195 sites

  Locations and eligibility →

• On zanubrutinib

  Sonrotoclax added to zanubrutinib

  Phase 3 · 261 sites

  Locations and eligibility →

• High-risk, no symptoms

  Early treatment

  Phase 3 · 633 sites

  Locations and eligibility →

See every recruiting CLL trial →

When the trials finish

Completion dates the trials registered. Results usually follow 3 to 12 months later.

What just happened

Standard treatment today

• Early, no symptomsWatch and wait; early treatment is being tested only in trials.
• Needs treatmentFixed-duration venetoclax-obinutuzumab or acalabrutinib-venetoclax, or a continuous BTK inhibitor (acalabrutinib, zanubrutinib, pirtobrutinib).
• High-risk (17p deletion, TP53)Continuous BTK inhibitor preferred.
• RelapsedSwitch class (BTK to BCL-2 or vice versa); pirtobrutinib after a covalent BTK inhibitor; CAR T-cell therapy for some.

See CLL trials recruiting now →