Measurable Residual Disease Testing Implementation Roadmap for Patients With ALL

J Clin Pathways. 2021;7(8):18-19.

Measurable Residual Disease Testing (MRD) can shape treatment choices and overall patient management to achieve better outcomes. Unfortunately, routine MRD testing is variable, and there are currently no standards for optimal MRD testing. To help address this deficiency, the Association of Community Cancer Centers (ACCC) developed the MRD Testing Implementation Roadmap for B-Cell Acute Lymphoblastic Leukemia (ALL), an innovative learning tool that can help multidisciplinary cancer care teams obtain the knowledge they need to implement, expand, and sustain MRD testing for adult patients with ALL.

This Roadmap provides information for health care professionals on how to lay the groundwork for MRD testing, train and prepare their care team to offer testing, implement testing, and evaluate ongoing progress.

Section 1: Laying the Groundwork

Cancer care teams must have a strong foundation to implement, expand, and sustain MRD testing at their institution. Items in this section of the Roadmap include:

• Learn the basics of MRD testing. MRD (also known as minimal residual disease) refers to the number of cancer cells that remain during and after cancer treatment. Complete remission (<5% blasts in bone marrow) by morphologic assessment is not enough to accurately depict remaining malignant cells. MRD speaks to deeper levels of sensitivity to detect disease. Monitoring a patient’s MRD at various points throughout active treatment and into remission provides important personalized insights into the effectiveness of a given therapy and may be used to predict which patients are at risk of relapse.
• Assess institutional buy-in. Hematologists/oncologists should lead MRD testing efforts and work with hematopathologists and/or pathologists to educate staff, including laboratory staff, on the role of MRD testing and methodology. The laboratory plays a critical role in identifying and creating relationships with reference laboratories for testing, which can impact costs to patients and/or the hospital system. Pathologists play an important role in evaluating tests and methodologies and reporting test results. To help determine infrastructure needs, institutions should: (1) consider expanding current molecular testing for MRD (eg, BCR-ABL); (2) review options for full MRD testing (eg, flow cytometry, next-generation sequencing, polymerase chain reaction); and (3) determine which method(s) to use and where to send samples (in-house and/or to external labs).
• Complete the pre-assessment. Download, review, and discuss the preassessment with core team members involved in MRD testing, then complete the pre-assessment online before starting project planning.

Section 2: Preparing the Care Team

In this section of the Roadmap, care teams:

• Learn how clinical and nonclinical staff are involved in MRD testing. Advanced practice providers often perform bone marrow biopsies, so these professionals should be familiar with the specific timing for MRD evaluation: MRD samples should be collected first instead of after morphology samples. Standardized order templates in the electronic health record (EHR) are critical to ensure appropriate samples are obtained for MRD at the appropriate time. Sometimes interventional radiologists do bone marrow biopsies, so they also should be educated about the importance of obtaining MRD from the first bone marrow sample. Pathologists have a critical role in implementing MRD testing, since they understand the nuances of testing and the implications for patient care. They ensure laboratory staff are prepared to handle specimens appropriately, validate testing, and coordinate send-out tests. At institutions where MRD testing is performed in-house, pathologists interpret and report test results to their oncology colleagues. Pathologists need to have a clear understanding of when to test for MRD and alert hematologists if they feel MRD is indicated but not ordered (ie, at the end of induction in ALL). Patient education about MRD is important, as it can be misconstrued that anything “negative” is bad.
• Assess staff and communication needs. This section includes tools and resources to help institutions understand project management, staffing, and communication and coordination needs around MRD testing. Here, care teams learn how to evaluate MRD testing efforts, including key metrics to review and measure (eg, the number of patients with ALL who had MRD testing done at the time of diagnosis and the number of patients with ALL who had MRD testing ordered on remission marrow [Day 30 bone marrow biopsy]).
• Develop a project plan. Key issues to address in this plan: (1) where to send samples, (2) how to develop and implement an MRD testing algorithm, (3) how to create a process for establishing insurance pre-authorizations, (4) how to develop and implement a process for ordering protocols, and (5) when and how to educate staff about new processes.

Section 3: Implementing MRD Testing

Implementing MRD testing requires different tools and resources for clinicians and patients. This section of the Roadmap addresses how care teams:

• Learn where to send samples for MRD testing. Institutions should have the following in place as they proceed with implementation: (1) institutional standards and/or algorithms for testing at each time point; (2) laboratory infrastructure to handle specimens, especially for send-out tests; (3) clear laboratory guidance on where to send tests; and (4) clear guidance to clinical staff regarding which samples they should pull at diagnosis. Note: interpretation of MRD testing results can be challenging as different vendors and labs have different ways of presenting results.
• Assess clinical workflow needs. These needs include standard operating procedures, EHR order sets, algorithms, lab requisition forms, and patient education materials.
• Pilot and refine the initiative. Tips for successful implementation of MRD testing include: (1) developing a standard algorithm for order of bone marrow aspirates; (2) detailing steps like storage conditions and shipping requirements in both paper and digital format; and (3) making an MRD training video and ensuring that team members watch at their own convenience.

Section 4: Evaluating Progress

It is important to continually evaluate progress. In this section of the Roadmap:

• Learn why evaluation is important. Evaluation allows for tracking of progress, as well as identification of areas where improvement is needed. Ideally, planning for evaluation should happen during development of the initiative. It is important to identify baseline data (if any are available), establish aim(s), develop metrics to measure success, and identify the types of data to be collected.
• Assess progress. Before beginning the post-assessment, download, review, and discuss it with the core team members involved in MRD testing.
• Share evaluation results. Regularly review and share MRD testing evaluation metrics. Create opportunities for leadership and team leads to get back together every 3 to 6 months to review the process, particularly as MRD testing continues to evolve. Consider: (1) how to share progress data internally during implementation to deepen the team’s commitment to the project; (2) at what stage to share results publicly with patients and caregivers as an example of the institution’s commitment to delivering the highest quality cancer care; and (3) when and how to share outcomes and lessons learned with peers to help build a broader knowledge base.