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Landgren Explains Crucial Role of MRD in Myeloma

Brandon Scalea
Published: Thursday, Dec 13, 2018

C. Ola Landgren, MD, PhD
C. Ola Landgren, MD, PhD
It is becoming clear that minimal residual disease (MRD) negativity is a crucial prognostic factor in patients with multiple myeloma, said C. Ola Landgren, MD, PhD.

It has been known that MRD has a role in clinical trials, but as more data become available, that role has become more clearly defined. For years, researchers have evaluated different platforms for detecting MRD in patients, and are now able to do so with the use of next-generation sequencing (NGS).

On September 28, 2018, the FDA approved the first NGS assay, ClonoSEQ, as a test for MRD in patients with acute lymphoblastic leukemia (ALL) or multiple myeloma. The clinical validity of the assay was shown in a retrospective analysis of samples collected from a clinical trial that enrolled 273 patients with ALL and 2 trials involving 323 and 706 patients with myeloma, respectively.

For the trials, researchers used the assay to evaluate MRD at various disease burden thresholds and determined that MRD status correlated with event-free survival (EFS). EFS was longer and EFS rates were higher for MRD-negative patients. These findings were similar for progression-free survival (PFS) and disease-free survival among patients with myeloma.1

Other data have shown that MRD negativity is indicative of longer PFS, irrespective of the treatment regimen used in a patient, said Landgren, chief of the Myeloma Service, Memorial Sloan Kettering Cancer Center, which is encouraging in the relapsed/refractory setting of myeloma.

Despite many options, there is still not an optimal therapy to use in the relapsed/refractory setting; however, chimeric antigen receptor (CAR) T-cell therapy has shown some promise in the space. For example, preliminary data from the phase I CRB-401 trial demonstrated that a BCMA-directed therapy, bb2121, induced a complete response rate of 50% in a heavily pretreated patient population. The median PFS was 11.8 months with a duration of response of 10.7 months. The phase II portion of the trial is ongoing.2

In an interview with OncLive, Landgren discussed the role of MRD negativity and the emergence of CAR T-cell therapy in multiple myeloma.

OncLive: What is the role of MRD in multiple myeloma?

Landgren: MRD is currently moving into many disease areas. In multiple myeloma, this has been going on for more than 10 years. Now, we are at a point that MRD plays a crucial role in clinical trials; it is an important clinical outcome. We have data from multiple studies and 2 meta-analyses showing that MRD negativity is indicative of longer PFS. We know that MRD negativity is a highly clinically meaningful prognostic marker in clinical trials. MRD negativity has been tested against cytogenetics and other important clinical markers and data show that MRD negativity is a stronger prognostic factor.

Additionally, there are now clinical trials showing that patients who achieve MRD negativity both in the newly diagnosed and relapsed/refractory settings have similar clinical outcomes; this is independent of the treatment arm they were on in the respective clinical trials. Simply, a 3-drug regimen versus a 2-drug regimen was being tested in a randomized matter. In both arms, there were patients achieving MRD negativity at some point. We looked at the patients' PFS outcomes. Data show that the patients who receive the more aggressive regimen have outcomes [similar to those who receive] the less aggressive regimen, as long as they achieve MRD negativity. 

Is there a specific assay for MRD testing that should be used across practices?

For a long time, researchers have been looking at different platforms for doing this. Some groups were in a laboratory trying to decide if we should use polymerase chain reaction primers based on the sequencing and the development of patient-specific primers. Over the years, the molecular field has evolved and moved forward very fast.

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