Can CLL Treatment Time Be Shortened with MRD Testing?

Venetoclax (Venclexta, AbbVie) and obinutuzumab (Gazyva, Genentech) are used as a fixed-duration first treatment for people with chronic lymphocytic leukemia (CLL), typically for 12 months. But what if some patients could safely stop treatment sooner?

A study presented by Dr. Meghan Thompson at the 2024 ASH conference suggests that treatment time can be adjusted based on minimal residual disease (MRD) test results. This could help personalize care, ensuring patients receive no more or less treatment than they need. 

Continue reading to learn how MRD testing may influence your CLL treatment path. 

What Is MRD Testing and Why Is It Important?

Minimal residual disease (MRD) testing checks for small numbers of remaining cancer cells after treatment. If the test doesn’t detect CLL cells, it's called undetectable MRD (uMRD). If cells are still found, it's called detectable MRD (dMRD).

The clonoSEQ test, used in this study, measured two levels of sensitivity:

• uMRD5 (10⁻⁵): Fewer than 1 CLL cell in 100,000 white blood cells
• uMRD6 (10⁻⁶): Fewer than 1 CLL cell in 1 million white blood cells

MRD can be tested using either blood or bone marrow samples, and results may differ slightly because the location of CLL cells can vary. 

How the Study Used MRD to Adjust Treatment Time

In this trial, 100 people with CLL received venetoclax and obinutuzumab for up to 24 months. How long they stayed on treatment depended on their MRD test results: 

• If patients had uMRD6 in blood by month 7, they were tested again at month 9. If they still had uMRD6, they stopped treatment early.
• If MRD was still detectable at month 7, they stayed on treatment and were retested at month 12.
• If uMRD5 was reached at month 12, treatment stopped.
• Patients who never reached undetectable MRD continued through the full 24 months.

At the end of treatment, everyone received a bone marrow MRD test to compare to their blood results.

What Were the Results?

• 50 patients stopped treatment by month 9 (uMRD6)
• 30 patients stopped by month 12 (uMRD5)
• 3 patients stopped at 24 months, with 1 reaching uMRD5
• The rest either left the trial, chose to continue, or didn’t meet the criteria to stop

By the 24-month mark, 92% of patients had not experienced cancer progression. There was no difference in outcomes between those who stopped early and those who stayed on therapy longer.

This shows that early MRD response can be a strong signal for when treatment can safely end.

Blood vs. Bone Marrow MRD: Are Results the Same?

While most results matched, they weren’t identical:

• Of those who had uMRD6 in blood by month 9, 70% also had uMRD6 in bone marrow
• For those with uMRD5 in blood by month 12, 68% had matching bone marrow results

This means blood testing alone is often—but not always—accurate. It still provides a strong, less invasive tool for guiding treatment decisions.

Do Genetic Features Influence MRD?

The study also looked at how CLL genetic traits affected MRD results:

• Patients with trisomy 12 were more likely to reach uMRD6 early
• Those with del13q were less likely to achieve early uMRD6
• Other markers like TP53 mutations, complex karyotypes, or IGHV mutation status didn’t make a big difference

This may help doctors understand who would benefit most from MRD-guided treatment.

What This Means for CLL Patients

This study supports the idea that MRD testing can personalize treatment duration for venetoclax and obinutuzumab in CLL. Some patients may stop therapy early and still enjoy long-term remission, while others may need the full course.

Additional takeaways: 

• MRD results from blood and bone marrow samples were mostly similar, but not always the same. This is why your care team may prefer to do both tests to monitor the cancer.
• Certain genetic traits may affect how quickly patients reach undetectable MRD.

It’s a promising step toward more tailored treatment plans. More research is underway to refine these approaches, especially for those who don’t reach undetectable MRD by month 12. 

Continue Exploring Advancements in CLL Treatments

Sources: 

• Minimal Residual Disease (MRD)-Adapted Duration of Front-Line Venetoclax and Obinutuzumab Treatment for Fit Patients with Chronic Lymphocytic Leukemia (CLL)
• 642. Chronic Lymphocytic Leukemia: Clinical and Epidemiological: Frontline Targeted Therapy Combinations