Rafael Fonseca, MD

Rafael Fonseca, MD, the Getz Family Professor of Cancer and Chair of the Department of Medicine, Mayo Clinic in Arizona and an expert in minimal residual disease (MRD) in myeloma, commented on the PRIMeR study for The ASCO Post.

The PRIMeR subanalysis of the STaMINA trial showed the prognostic ability of MRD status for both progression-free and overall survival, “like other previous publications.” But in this study, the magnitude of difference in outcomes “is such that the hazard ratios reported are the greatest ever reported in myeloma, superior to that of genetic prognostic factors,” Dr. Fonseca said.

“It should be noted that achievement of MRD-negative status is in and of itself an outcome that will subsequently predict a secondary one (ie, is a surrogate marker),” he said. “Although not completely determinant of the long-term prognosis, MRD status seems to hold the greatest ability of any marker to predict long-term outcomes. Previous work by the Spanish PETHEMA groups had shown that achieving a complete response but remaining positive in MRD testing was not clearly different from achieving a very good partial response.”

MRD testing in myeloma has been approved by the U.S. Food and Drug Administration, although it has not yet been fully accepted for regulatory purposes, he added. But the growing body of literature suggests it could expedite the time to obtain approval for proposed new medications or interventions, Dr. Fonseca added. It should be noted that its main use lies in determining the depth of response at the completion (or during) initial therapy; it is used less so for second and third lines of therapy, although it may still apply in these settings in the future, he added.

Could MRD Negativity Eliminate the Need for Transplant?

“One aspect of these data is that achievement of MRD is the goal, irrespective of the path that leads there. In other words, if this were to be further validated, one could envision a future for myeloma therapy that is devoid of stem cell transplant. If a treatment strategy achieves a rate of MRD negativity that is similar or superior to that of other strategies that incorporate a transplant, clinicians will consider omission of transplant as part of the regimen,” Dr. Fonseca suggested.

“Is this ready for widespread adoption? Probably not, but as more and more publications consistently show the power of MRD negativity as a prognostic factor, the question will be knocking on our doors,” Dr. Fonseca concluded.

“Will we need large, randomized phase III studies to omit transplant in the future? That is hard to tell,” he noted, “and it is for the myeloma community to decide what additional trials are needed. However, it is not difficult to envision a decrease in stem cell transplant as primary therapy for myeloma. Before the innovators prevail, transplant physicians will be quick to point out that in this trial, those who received a tandem transplant seemed to have a higher rate of MRD negativity than those who had a single transplant alone. That is a question for another day.” ■

DISCLOSURE: Dr. Fonseca is a consultant with Amgen, BMS, Celgene, Takeda, Janssen, AbbVie, Phaarmacyclics, Merck, Sanofi, Kite, and Juno; has served on the scientific advisory board for Adaptive Biotechnologies; and Mayo Clinic holds the patent in his name for the prognostication of MM based on genetic categorization of the disease.