Saad Z. Usmani, MD
Although the importance of achieving minimal residual disease (MRD) negativity in patients with multiple myeloma has been established, further application in practice is dependent on phase III findings from ongoing trials, explains Saad Z. Usmani, MD.
“The next step is utilizing MRD as a potential surrogate for survival to then stop therapy or determine if something more needs to be done to achieve MRD negativity in a given patient,” said Usmani, who is clinical professor of medicine, UNC-Chapel Hill School of Medicine, chief, Plasma Cell Disorders Program, director, clinical research in hematologic malignancies, Levine Cancer Institute, Carolinas HealthCare System.
In an interview during the 2018 OncLive®
State of the Science SummitTM
on Multiple Myeloma and Myeloproliferative Neoplasms, Usmani, who was chair of the program, discussed the clinical applications of MRD and managing patients with relapsed/refractory multiple myeloma.
OncLive: Please provide an overview of your presentation.
I spoke about MRD, the importance of depth of response in myeloma, and where that data come from. Then, I segued into some clinical data with prospective clinical trials looking at MRD negativity with different methodologies. There [are many] unanswered questions. Ultimately, MRD status should not be used to change treatment.
[We should] be on the lookout for the clinical trials that are asking those kinds of questions. If a patient has been on lenalidomide (Revlimid) maintenance for 3 years and they're MRD negative, can we stop treatment in those patients, or do we continue lenalidomide maintenance forever?
After a very robust induction treatment with the conventional 3 drugs we use—bortezomib (Velcade), cyclophosphamide, and dexamethasone (CyBorD); lenalidomide, bortezomib, and dexamethasone (RVD); or even carfilzomib (Kyprolis), lenalidomide, and dexamethasone (KRd)—[can we] combine them with a CD38-targeted monoclonal antibody or anti-SLAMF7 monoclonal antibody? If we're achieving MRD after induction in a sizable number of patients, do they really need an autologous stem cell transplant? These are the questions we need to ask in clinical trials; however, they don't influence our practice as of now.
Does your initial treatment approach differ in patients who have MRD-positive disease versus MRD-negative disease?
For standard-risk patients, my clinical practice does not change. For high-risk patients, you have to be on high alert because any level of residual disease means that those patients will be at a high risk of relapse. That's where surveillance becomes important. In those patients, an early change in treatment is likely when we would make those treatment decisions. As a clinician, that's where I feel I can use MRD data. Outside of that, we still need to wait for the clinical trials to read out and help us understand what MRD positivity or negativity means in the context of clinical practice.
For high-risk patients, what does surveillance entail?
These patients should be getting monthly myeloma markers. If they're in the maintenance setting, they are usually on more intensive maintenance regimens than standard-risk patients. They might be on both a proteasome inhibitor as well as an immunomodulatory drug. If they were presenting with extramedullary disease, it may be reasonable to evaluate with PET-CT scans once or twice a year during the surveillance period. I wouldn't make that recommendation for someone who has standard-risk disease, but with high-risk patients you have to be a little bit more vigilant.
What does the timeline look like for trials examining MRD as an endpoint?
One European clinical trial looked at a bortezomib-based triplet induction regimen with or without daratumumab (Darzalex) following transplant. That particular clinical trial had MRD endpoints built into it. The IFM 2009 trial also had MRD endpoints built into it, but maintenance was restricted in the IFM 2009 study. Within the IFM 2009 study, MRD was evaluated at different endpoints. We have learned about the postinduction and posttransplant data, but we are still waiting on some long-term follow-up data to see how MRD patterns evolved in each of those 2 arms.