How MRD Status Could Help Predict Outcomes for People with High-Risk ALL

Minimal residual disease (MRD) is a measurement of the number of cancer cells that remain in the body after treatment. A person is considered to be MRD negative when there are no detectable cancer cells are found in the blood or bone marrow. MRD is an important measurement for acute lymphoblastic leukemia. New research suggests that doctors can use this measurement to help predict outcomes for people with B-cell acute lymphoblastic leukemia (B-ALL). B-ALL is the most common type of ALL.

Recent research published in Nature has shown how a highly sensitive MRD test using next-generation sequencing (NGS) can be used to predict outcomes for patients with B-ALL. Understanding the impact of MRD negativity on overall outcomes will help in decision-making about the best path for care after diagnosis.  

How researchers studied the impact of MRD on B-ALL outcomes

The study looked at 161 patients with B-cell ALL who had been treated between 2016 and 2024. Using NGS, researchers measured the amount of MRD. NGS is a technology used to find variants or mutations in RNA and DNA. It’s highly sensitive and can be used to find any remaining cancer cells in the body. MRD negativity is an important measure for outcomes in ALL because it provides information early about how the cancer is responding to treatment. 

Researchers stratified the results based on whether or not the patient had Philadelphia chromosome rearrangement. Stratifying results helps researchers understand how the studied intervention affects specific types of patients. 

Philadelphia chromosome (PH) rearrangement refers to an aggressive type of ALL. These patients have a genetic change called the BCR-ABL1 fusion gene. This produces too much of the tyrosine kinase protein and drives cancer growth. 

Of the study participants, 32% had PH-positive (PH+) ALL and 68% had PH-negative (PH-) ALL.  

Those with PH- ALL received a hyper CVAD-based regimen. This is a combination therapy consisting of cyclophosphamide, vincristine sulfate, adriamycin, and dexamethasone. Those with PH+ ALL received a chemotherapy-free regimen consisting of blinatumomab plus a BCR-ABL1 tyrosine kinase inhibitor (TKI).  

MRD negativity increased among participants over time

MRD negativity is associated with long-term survival and reduced risk of relapse. 

The study found that the sooner MRD negativity is achieved, the better long-term outcomes are for people with B-ALL. For people with PH+ ALL, 38% achieved MRD negativity immediately after induction therapy. After 3 months, 72% had achieved MRD negativity. After 6 months, 84%.

For people with PH-ALL, 30% achieved MRD negativity immediately after induction therapy. After 3 months, 63%, and after 6 months, 82% had achieved MRD negativity. 

MRD negativity among high-risk patients

There are some baseline features of cells and molecules that can predict worse outcomes in people with ALL. These high-risk features include: 

• Low hypodiploidy/near triploidy
• Five or more chromosomal abnormalities
• KMT2A rearrangement
• PH-like ALL
• TP53 mutation

For patients in the study with high-risk features, MRD negativity rates were similar to those of standard-risk patients. 

For high-risk patients, 36% achieved MRD negativity right after induction therapy. After 3 months, 62% had achieved MRD negativity. After 6 months, it was 85%. 

For standard-risk patients, 25% achieved MRD negativity right after induction therapy. After 3 months, 64% had achieved MRD negativity. After 6 months, 79%. 

MRD-negative patients had higher rates of relapse-free survival 

Relapse-free survival (RFS) refers to the timeframe after treatment that a patient lives without any return of symptoms.  

Overall, RFS was higher among MRD negative patients. This shows how this measurement can be used to predict prognosis for people with ALL during their treatment. 

The 2-year RFS for MRD negative patients was:

• 94% after induction
• 82% after 3 months 
• 82% after 6 months

The 2-year RFS for MRD positive patients was:

• 66% after induction
• 65% after 3 months
• 62% after 6 months 

This study sheds important light on the way that MRD negativity impacts survival in patients with ALL. A deeper understanding of when patients tend to reach MRD negativity can make a significant impact on treatment planning.  

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Sources:

• Nature-NGS MRD dynamics in Prognosis for B-cell ALL 
• NIH-B-cell ALL Defined 
• HealthTree-MRD Negativity in ALL 
• NIH-Relapse-free survival Defined