Single assessments of minimal residual disease (MRD) effectively prognosticated relapse risks in patients with MCL treated with chemoimmunotherapy and transplantation, according to investigators.
Dr. Simone Ferrero
However, by evaluating MRD status over time, disease progression could be predicted with greater certainty, according to study lead author Simone Ferrero, MD, assistant professor of hematology at the University of Torino (Italy).
“The most important message is that MRD is predictive, and then in particular, if you want to study MRD, you have to do a repeated MRD analysis in order to have a better picture of the disease course and to determine the prognosis of each single patient,” Dr. Ferrero said in an interview.
Predictive power of MRD
Piers Blombery, MBBS, hematologist and medical lead of the Molecular Hematology Laboratory at Peter MacCallum Cancer Centre in Melbourne, said these study findings illustrate how the predictive power of MRD is enhanced when it is evaluated longitudinally, over the course of a patient’s disease.
“We need to be prepared to have models of MRD that take into account changes in values across time,” Dr. Blombery said in an interview.
“Conventionally, we have looked at single time points in disease, such as end of induction therapy or post autologous stem cell transplant,” said Dr. Blombery, “but we may need now to have more complex models that can integrate values over multiple time points to guide intervention.”
Dr. Blombery, who was not involved in the study, coauthored an independent commentary on the results that was also published in Blood.
Tools to predict relapse
Although initial MCL treatment is often effective, most patients will relapse. Accordingly, there have been considerable efforts to develop tools that identify patients at high risk of relapse, according to Dr. Ferrero and coauthors.
Among these tools is the Mantle Cell Lymphoma International Prognostic Index (MIPI), which risk-stratifies patients on the basis of age, performance status, leukocyte count, and lactate dehydrogenase.
More recently, in several published studies, MRD has been demonstrated a high predictive value in MCL. However, the best way to evaluate MRD has yet to be worked out. There are differences in testing methods, sampling (that is, bone marrow versus peripheral blood), and time points that are evaluated.
In some recent studies, investigators have pooled MRD samples taken at different time points, according to Dr. Ferrero and colleagues. Furthermore, there had been no prior systematic attempts to compare the prognostic performance of MRD data evaluated over time, as compared with MRD at a single time point.
Exploiting MRD data
The analysis by Dr. Ferrero and coauthors, which appears in the journal Blood, is a substudy of FIL MCL0208, a recent multicenter, randomized, phase 3 clinical trial that demonstrated the benefit of lenalidomide maintenance over observation following autologous stem cell transplantation (ASCT) among 300 patients with MCL in Italy and Portugal.
In the study, investigators monitored MRD in both peripheral blood and bone marrow at 10 fixed time points throughout treatment (including induction, consolidation, post ASCT, and then every 6 months during maintenance and follow-up), yielding 4,351 individual MRD results.
Individual MRD analyses were prognostic in MCL, according to the investigators, with results that were relevant to disease progression right after ASCT, and were most predictive starting at 6 months after ASCT.
However, the best way to exploit the bulk of MRD information that had been collected, investigators said, was a model that combined regularly updated MRD results with MIPI scores.
This MIPI-adjusted model, based on MRD assessed in bone marrow by real-time quantitative polymerase chain reaction (RQ-PCR), outperformed both MIPI and a MIPI-adjusted single time-point analysis in terms of predicting time to progression.
The predictive power of the MIPI-adjusted bone marrow RQ-PCR analysis was illustrated by an area under the curve of 0.85-0.87, compared with an AUC of just 0.60-0.63 for classic MIPI analysis, 0.62-0.65 for MIPI-adjusted MRD at a post-ASCT time-point analysis, and 0.74-0.77 for MIPI-adjusted MRD at 6 months from transplant.
Peripheral blood ‘easier to collect’
Although bone marrow analysis performed best in the single-point MRD evaluations, looking at MRD over time greatly improved the predictive power of the peripheral blood MRD results, yielding an AUC up to 0.81, according to the report.
This enhancement of peripheral blood performance is a finding that may have important clinical implications, according to Dr. Ferrero, considering that peripheral blood monitoring is more practical for long-term, repeated MRD monitoring.
“It is interesting, because peripheral blood is easier to collect than bone marrow,” Dr. Ferrero said. “So if you plan in your analysis to monitor MRD in peripheral blood every 6 months, then you can have a predictive value similar to that of one single point in bone marrow.”
Dr. Ferrero provided disclosures related to Janssen, EUSA Pharma, Gilead, Morphosys, Incyte, Clinigen, Servier, and Gentili. The other authors reported no relevant conflicts of interest.