Addressing Barriers to Implementing MRD Testing in Community Oncology Practices

Georges Azzi, MD

Holy Cross Health

Several barriers exist to implementing minimal residual disease (MRD) testing in community oncology practices, including a desire for additional prospective data, and a lack of awareness of its benefits, according to Georges Azzi, MD.

In an interview with CancerNetwork^®, Azzi, an oncologist at Holy Cross Health, indicated that MRD testing is a valuable tool for treatment decision making for lymphoid malignancies.

“I’ve been practicing medicine for over a decade, and during this time I’ve had an opportunity to see exactly how advanced technologies like MRD testing can shape the way we support patients with lymphoid malignancies,” he said. “New advances in treatment are driving deeper responses and are requiring the deepest measurement tool to ensure we are providing each patient with the longest possible remissions.

“When treating patients with cancer, we should be using every tool in our toolbox. By raising awareness of the value of MRD testing, we can empower oncologists to attain a more comprehensive understanding of their patients’ disease and develop personalized treatment plans tailored to individual needs.”

CancerNetwork^®: How has MRD testing impacted clinical decision making within your practice?

Azzi: As a practicing community oncologist in South Florida, I’ve been using MRD testing for approximately 3 years. While different types of MRD testing methods are available, I use a next-generation sequencing (NGS) based test called clonoSEQ^® because it can detect cancer cells that remain after treatment at 10^-6, which is the deepest level currently available. The test’s ability to provide a dynamic measure of risk status in real-time has helped me personalize treatment decisions depending on the needs of each patient.

Initially, I started using NGS testing for solid tumors, but I was really interested in finding a test that worked similarly in blood cancers. Once I found clonoSEQ, I began using it with patients diagnosed with chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), and multiple myeloma. The specificity of the test enables me to predict outcomes, vigilantly evaluate response to treatment, and in turn, make treatment decisions confidently. These decisions can include discontinuing treatment early, escalating or de-escalating therapy, or adjusting the patient's monitoring frequency. Plus, my patients seem to gain additional confidence in their treatment plans and overall peace of mind as a result of clonoSEQ MRD testing.

Could you go into detail about how MRD testing is being used to guide treatment decision-making?

An MRD test detects, quantifies, and tracks the number of cancer cells that remain in the body during and after cancer treatment. Using this information, oncologists can gain insight into both the depth of response to a treatment, as well as detect early signs of relapse in patients with lymphoid malignancies. These insights provide us with a better understanding of the long-term outcomes for each patient. MRD testing at multiple time points helps me more dynamically assess patient prognosis and risk of likely relapse.

MRD testing also helps oncologists monitor and assess response to therapy over time. Based on the test results, I might choose to re-evaluate patients to better understand if they need to stop or re-start treatment. I also use it to inform my decisions about whether a patient can de-escalate therapy or end maintenance therapy. In my practice, I might see patients with multiple myeloma who have been on maintenance for an extended period of time and are often experiencing adverse effects or requesting a treatment holiday. If these patients have sustained MRD negativity, I would feel confident reducing or stopping therapy and monitoring them closely for an MRD resurgence. Conversely, if the patient is MRD-positive, I would consider the next steps in this patient's treatment plan. Either way, I am utilizing MRD to personalize the treatment plan for each patient.

What are the challenges with implementing MRD testing in the community setting?

Today, MRD testing is more frequently performed in academic medical centers and in clinical trials than in community oncology practices. One of the major barriers to adoption in the community setting is related to the general level of awareness of the test, its benefits, as well as actionability of the test results in the related disease state. This is exemplified when we compare the application of MRD testing in solid tumors and lymphomas. In solid tumors, even the slightest presence of disease can pose a problem.

However, some lymphoid malignancies may be more akin to a chronic disease. In the chronic setting, this result informs the need to monitor the patient more frequently. Whereas in acute diseases, an MRD-positive result is a crucial component in initiating the next steps for a patient.

Another barrier to adoption is the desire for additional prospective data regarding the actionability of MRD testing. As oncologists, we always desire more data, but we are skilled at making decisions in our patients’ best interest based on the data that currently exist.Numerous studies highlighting the direct applications and advantages of this test have been published and are still being conducted. Overcoming this obstacle may simply require additional educational efforts pointing doctors to available and continuously emerging resources.

When adopting any medical test, the potential cost is often a concern for patients and, in turn, their physicians. Luckily, clonoSEQ is covered by Medicare, has a great patient support program, and is relatively inexpensive compared with other NGS tests. Especially when considering the broader perspective, the cost of the test is significantly lower than the expenses incurred by administering unnecessary treatment.

How might these barriers be addressed?

MRD testing is an incredibly valuable tool for painting a more complete picture of a patient’s disease—better equipping us to make critical decisions based on each patient’s trajectory. Adding MRD testing into a community oncology practice is far easier than it may be perceived. The tests are straightforward to order, and their results are easy to interpret. I highly encourage community oncologists to tap into their network to learn more about best practices related to adoption. This includes exploring community oncology resources, such as NCODA’s positive quality interventions (PQIs) for multiple myeloma and CLL, and connecting with peers across both academic and community settings who have successfully implemented MRD testing.^1,2

Further, there are several resources, particularly in the form of both complete and ongoing clinical studies, that can offer valuable insights into the applications and advantages of MRD testing. A few of the most notable studies include IFM 2009, DETERMINATION, and MASTER,^3-5 which provide insights into where MRD should be considered post induction, post transplant, during and post consolidation, and during and post maintenance therapy. Several ongoing studies such as DRAMMATIC (SWOG 1803) and AURIGA are actively assessing the use of MRD to guide clinical decisions.^6,7

Where should research be focused to push the needle forward for MRD testing?

Advancing MRD testing in cancer treatment requires a focused research approach, particularly on integrating MRD testing into clinical practice. This involves determining the optimal timing and frequency of MRD testing and how its results should influence treatment decisions, along with evaluating the impact of MRD-guided therapy on patient outcomes. Research should also further explore health care system cost savings based on MRD-guided clinical decision making, aiming to minimize patient financial toxicities associated with both short- and long-term cancer treatment.Investigating the predictive value of MRD in different cancer types, particularly in predicting treatment responses and patient outcomes, is vital. Additionally, understanding the effect of MRD testing on patient-reported outcomes, such as quality of life and psychological health, is crucial.

References

1. NCODA. Positive Quality Intervention: clonoSEQ Next Generation Sequencing for Minimal Residual Disease Testing in Multiple Myeloma. 2023. Accessed December 19, 2023. https://bit.ly/41ATRPd
2. NCODA. Positive Quality Intervention: clonoSEQ® Next Generation Sequencing for Minimum Residual Disease Testing in Chronic Lymphocytic Leukemia. 2023. Accessed December 19, 2023. https://bit.ly/41qFddj
3. Attal M, Lauwers-Canes, Hulin C, et al. Lenalidomide, bortezomib, and dexamethasone with transplantation for myeloma. N Engl J Med. 2017;376:1311-1320. doi:10.1056/NEJMoa1611750
4. Richardson PG, Jacobus SJ, Weller EA, et al. Triplet therapy, transplantation, and maintenance until progression in myeloma. N Engl J Med. 2022;387:132-147. doi:10.1056/NEJMoa2204925
5. Costa LJ, Chhabra S, Medvedova E, et al. Daratumumab, carfilzomib, lenalidomide, and dexamethasone with minimal residual disease response-adapted therapy in newly diagnosed multiple myeloma. J Clin Oncol. 2021;40(25):2901-2912. doi:10.1200/JCO.21.01935
6. SWOG Cancer Research Network. Phase III Study of Daratumumab (NSC- 791647) + Lenalidomide (LD) or Lenalidomide (L) as Post-Autologous Stem Cell Transplant Maintenance Therapy in Patients with Multiple Myeloma (MM) Using Minimal Residual Disease to Direct Therapy Duration (DRAMMATIC Study). 2023. Accessed December 19, 2023. https://bit.ly/3vdy7g1
7. Shah N, Patel S, Pei H, et al. Subcutaneous daratumumab (DARA SC) plus lenalidomide versus lenalidomide alone as maintenance therapy in patients (pts) with newly diagnosed multiple myeloma (NDMM) who are minimal residual disease (MRD) positive after frontline autologous stem cell transplant (ASCT): The phase 3 AURIGA study. J Clin Oncol. 2021;39(suppl 15). doi:10.1200/JCO.2021.39.15_suppl.TPS8054