Technologies for Monitoring Minimal Residual Disease May Help Predict Outcomes for Patients with Leukemia
New evidence suggests that using advanced genetics technologies to monitor for remaining cancer cells after treatment may soon become an effective tool to inform treatment decisions and ultimately predict patient outcomes for patients with a particularly aggressive form of acute lymphocytic leukemia (ALL). Study results were published online today in Blood, the journal of the American Society of Hematology.
Approximately 25% to 30% of all adults with ALL have Philadelphia chromosome–positive disease, a rapidly progressing form of ALL that is associated with a poor prognosis. The development of tyrosine kinase inhibitors has lead to greatly improved survival rates for some patients, but clinicians lack a reliable method for predicting disease progression and determining whether a patient’s disease is aggressive enough to warrant an allogeneic stem cell transplant or if tyrosine kinase inhibitor therapy plus chemotherapy will likely eradicate the disease.
Data from several recent studies have suggested that monitoring minimal residual disease may be an effective indicator of a patient’s risk of relapse. Consequently, clinicians have increasingly employed several highly sensitive monitoring tools to detect minimal residual disease, such as multiparameter flow cytometry and real-time quantitative polymerase chain reaction. Although this method has proved effective for several other types of leukemia, the reliability of these tools specific to Philadelphia chromosome–positive ALL is not yet fully understood.
Study Details
To better understand how technology that tracks indicators of minimal residual disease could potentially predict Philadelphia chromosome–positive ALL patients’ survival and inform treatment decisions, lead study author Farhad Ravandi, MD, of The University of Texas MD Anderson Cancer Center, and colleagues conducted a decade-long study to monitor whether a negative minimal residual disease reading was associated with prolonged survival.
Between 2001 and 2011, Dr. Ravandi’s team monitored 76 adult patients (median age, 54 years) with Philadelphia chromosome–positive ALL who had achieved complete remission after a treatment regimen including at least one course of induction chemotherapy plus a tyrosine kinase inhibitor followed by treatment with either dasatinib (Sprycel) or imatinib (Gleevec) and chemotherapy, and 2 years of tyrosine kinase inhibitor maintenance therapy.
All study participants began with fewer than 5% cancer cells in their body and none had undergone stem cell transplant, nor were they at an otherwise heightened risk of relapse. Utilizing multiparameter flow cytometry and real-time quantitative polymerase chain reaction technologies, investigators monitored patients for minimal residual disease after first remission and every 3 months thereafter.
Results from the investigation suggested that when used together, the monitoring technologies were effective in predicting the majority of disease progression and patient outcomes in this population. Among 44 patients who showed evidence of minimal residual disease in the first year of follow-up (either by multiparameter flow cytometry and real-time quantitative polymerase chain reaction results), 13 relapsed, including 9 of 22 of the highest risk patients who showed positive multiparameter flow cytometry at 3 months and beyond. Thirteen of 54 patients who maintained negative minimal residual disease from 3 months and beyond had relapsed.
Potentially Valuable Prognostic Tool
Although the minimal residual disease readings observed by Dr. Ravandi and his team did not accurately predict all patient outcomes in the study population, the researchers noted that these results indicate that the combination of multiparameter flow cytometry and real-time quantitative polymerase chain reaction technologies represents a valuable prognostic tool to measure the likelihood of a patient relapse. However, they caution that it is too early to integrate the use of these technologies into treatment guidelines regarding the necessity of stem cell transplant for patients with Philadelphia chromosome–positive ALL.
“While our results aligned with our observed outcome in this study and the [multiparameter flow cytometry and real-time quantitative polymerase chain reaction] technologies are very sensitive, these tools do not yet provide absolute results. We advise that each treatment decision be made on a patient-to-patient basis to take into account each patient’s different genetics,” said Dr. Ravandi. “The next step is to refine and standardize our approach to better define which patients are truly disease-free and who should be recommended for more aggressive treatment.”
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
