Survival May Be Possible for Patients With CLL Even With Small Amounts of Disease After Treatment

Patients with chronic lymphocytic leukemia (CLL) who have a very small number of cancer cells left after Imbruvica (ibrutinib)-based therapy may still have prolonged survival without cancer progression.

Minimal residual disease (MRD), according to the National Cancer Institute, describes a small number of cancer cells that remain during or after treatment and is assessed using highly sensitive lab methods that can find one cancer cell among a million normal cells. MRD testing, which is mostly used for blood cancers, can be used to plan treatment, assess how a treatment is working, determine whether cancer has returned or make a prognosis.

“We now know ... that even if (MRD) is detectable, it does not appear to be as concerning for patient clinical outcomes to therapy as if it would be in the setting of receiving (chemoimmunotherapy),” Dr. Neil E. Kay, a consultant and professor of medicine at Mayo Clinic in Rochester, Minnesota, told CURE ®. “In addition, we can now use the levels of (MRD) to assist us in predicting which patients will have better outcomes.”

Studying MRD in CLL is not an entirely new focus in research. “The detection of residual but measurable CLL disease, designated traditionally as detection of minimal residual disease, has been the subject of studies in CLL for many years,” Kay said. “This is because we want to know if there (are) any remaining CLL cells after a certain time on therapy where we cannot detect CLL by routine measures such as physical exam and imaging. This can be done in that situation by monitoring for MRD in patients’ blood.”

Kay added that there are some existing beliefs about minimal residual disease.

“It is thought ... that if CLL patients are negative for (minimal) residual disease (called undetectable MRD) by sensitive laboratory techniques like flow cytometry, they will do better than if there is obvious residual disease by usual clinical assessment,” he said.

In the trial published in Blood by Kay and his team, patients treated indefinitely with Imbruvica and six cycles of Rituxan (rituximab) had a longer progression-free survival (the time during and after treatment when a patient lives with cancer without worsening) compared with those treated with six cycles of chemo- immunotherapy, particularly if they had undetectable MRD periodically up to 36 months.

They also found that patients treated with Imbruvica and Rituxan who had detectable MRD did not have significantly worse progression-free survival versus those with undetectable MRD. In addition, patients with lower levels of MRD had longer progression-free survival versus those with higher levels of MRD.

“The use of sequential testing of MRD for patients treated with (Imbruvica and Rituxan) was of value in predicting clinical outcomes in two ways,” Kay said. “For patients with detectable MRD, they did not have a worse progression rate than those with undetectable MRD. Also, we found that patients with a very low but still detectable MRD level had a longer progression-free status than those that were at higher MRD levels. These are new findings for the value of MRD ... in previously untreated CLL patients.”

Although this trial provided some insight into MRD, more answers are needed, Kay said.

“The additional questions that remain are the following: Are there better ways to measure MRD?” he asked. “What is the best timing for testing MRD in treated patients? Can you use MRD levels to decide on stop- ping a specific therapy, or can you use MRD levels to determine if a patient’s clinical response is fading and will now need additional treatments?”

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