EXPERT ANALYSIS FROM A MEETING ON HEMATOLOGIC MALIGNANCIES
NEW YORK (FRONTLINE MEDICAL NEWS) – Testing for minimal residual disease is clearly the state-of-the-art way to gauge the status of treated patients with multiple myeloma, agreed experts. The issue now is whether reliance on MRD to guide management remains investigational or ready for routine practice.
Paul G. Richardson, MD, gave MRD full endorsement as the wave of the future, but cautioned against routine use right now. “MRD is an exciting new tool [but] is not yet the standard of care for routine practice,” he said at the conference held by Imedex.
Perhaps the biggest advantage of MRD is that evidence indicates it is an excellent barometer of a patient’s prognosis. Data show that patients with undetectable MRD, generally measured in bone marrow cells, have a significantly reduced risk for progression and death, compared with patients who harbor detectable residual disease, said Dr. Richardson , professor of medicine at Harvard Medical School and clinical program leader of the Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute in Boston.
He cited results from a recent meta-analysis that included data from 14 studies of multiple myeloma patients that examined the correlation of MRD status with progression-free survival and 12 studies that addressed how MRD related to overall survival. The meta-analysis results showed that, among patients in complete remission, the average duration of progression-free survival was 56 months in patients who began follow-up without detectable MRD and 34 months in patients with detectable MRD ( JAMA Oncology. 2017 Jan;3[1]:28-35 ). The average duration of overall survival was 112 months in patients with undetectable MRD and 82 months in those with detectable MRD.
But MRD assessment still has several limitations. Evaluations of its strength for prognosis have largely been based on flow cytometry measures of MRD, an approach recently eclipsed by next-generation sequencing and polymerase chain reaction–based assays. Lack of standardization across the multiple tests now available is another hindrance. In addition, undetectable MRD in a myeloma patient in no way means that the malignancy is gone and that treatment can stop. Patients with undetectable MRD may have better medium-term outcomes, compared with patients with detectable MRD, but even patients with undetectable multiple myeloma still succumb to disease progression several years later.
“Patients negative for MRD do better than patients with detectable MRD, but they still relapse and die. You must maintain treatment in patients negative for MRD,” Dr. Richardson said. The clinical experience “supports the idea that, going forward, MRD has real potential, but MRD is not yet standard of care for routine practice,” he said.
In late 2015, Memorial Sloan-Kettering Cancer Center began routinely using MRD to assess multiple myeloma patients, said C. Ola Landgren, MD , PhD, professor of medicine at Weill Cornell Medical College and chief of the Myeloma Service at Memorial Sloan-Kettering.
“In our practice, we started about 18 months ago with MRD-directed treatment as our standard of care, although we don’t have data from a phase III trial” to prove the efficacy of this approach, Dr. Landgren explained.
He and his associates focus on newly diagnosed multiple myeloma patients who have undergone induction therapy. Patients who come out of the regimen with an undetectable level of MRD at a sensitivity of one cell in a million have the option of receiving high-dose melphalan (Alkeran) followed by autologous stem cell transplantation or maintenance therapy with lenalidomide (Revlimid). Patients who finish induction with detectable MRD can either receive immediate treatment with high-dose melphalan followed by autologous stem cell transplantation or further combination treatment with lenalidomide, carfilzomib (Kyprolis), and dexamethasone, then followed by melphalan and stem cell transplantation ( Bone Marrow Transplantation. 2016 July;51[7]:913-4).
“The data show that patients who become MRD negative have longer progression-free survival and overall survival, and we find that more and more patients achieve a MRD-negative state,” said Dr. Landgren. “In our practice, it’s about half of newly diagnosed patients. I think that achieving MRD negativity is more important than the specific treatment a patient receives” for predicting prognosis, he said.
Dr. Richardson has been a consultant to Celgene, Genmab, Janssen, Novartis, Oncopeptides, and Takeda and has received research funding from Celgene and Takeda. Dr. Landgren has been a consultant to Amgen and Takeda and a speaker on behalf of Plexus.
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