Photo Credit: Nemes Laszlo
A panel of 10 expert hematologists created recommendations for optimal MRD-guided ALL treatment, which were recently published in Blood Advances.
When acute lymphoblastic leukemia (ALL) occurs in adult patients, studies have shown that the most compelling prognostic tool is measurable residual disease (MRD). MRD assessment is consistently accurate in its predictive application across ALL subtypes, the timing of MRD assessment, varying clinical contexts, and the specific type of MRD assay applied.
Despite the confirmed value of MRD, many questions remain regarding its use, including variation among assays, cytomolecular features, and potential therapeutic interactions. To address these and other issues regarding the use of MRD as a prognostic tool in ALL, a panel of 10 experts in the field was assembled and tasked with developing recommendations regarding the optimal use of MRD in adults with ALL. The results of this collaboration were published in Blood Advances.
Before the panel’s work commenced, a systematic literature review targeting retrospective and prospective English studies on MRD and ALL was used to develop the questions to be focused on by the panel. One of the panelists, Nicholas Short, MD, discussed the findings and recommendations of this group of experts with Physician’s Weekly (PW).
PW: What challenges exist in using MRD assessment to guide decision-making in ALL?
Dr. Short: MRD assessment is critical to risk stratification in ALL. However, the literature lacked guidance on how this information should inform therapeutic decision-making, such as selecting patients for allogeneic stem cell transplantation. The recent development of very high-sensitivity MRD assays (such as the next-generation sequencing-based clonoSEQ assay) has complicated these issues since there are fewer published studies describing the dynamics of MRD using this assay and how very low levels of MRD detected by clonoSEQ should inform treatment decisions.
What are the most important recommendations developed by the panel?
The panel recommends that most clinical decision-making should be based on clonoSEQ testing, which is the most sensitive MRD assay we have for ALL. We also provided guidance for the optimal frequency of MRD testing in ALL, the use of blood versus bone marrow MRD assessment, and how this information can inform decisions for allogeneic stem cell transplantation or MRD-directed therapies.
What knowledge gaps remain regarding MRD use during ALL treatment?
Large prospective studies are needed to better understand the dynamics of MRD across novel regimens being developed for patients with ALL (eg, regimens that incorporate blinatumomab, inotuzumab ozogamicin, and/or CAR T-cells) so that these recommendations can be refined in the future. We also need more data on whether the achievement of deep MRD negativity using the clonoSEQ assay may overcome the poor prognosis of patients with high-risk cytomolecular features and the impact of NGS-based MRD using clonoSEQ in T-cell ALL, among other pressing questions.
What else should clinicians know about using the clonoSEQ assay?
An important section of these recommendations focused on interpreting clonoSEQ results, which can be challenging. Proper interpretation of this assay (which is now becoming the most common way to assess MRD in ALL in the US) is imperative to avoid overtreating a patient with “false positive” MRD results.
