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ASH 2015: We ask Professor Sagar Lonial (Emory University School of Medicine, Atlanta, USA) what the role of PET/CT is as a measure of MRD post ASCT and ask Professor Antonio Palumbo (University of Torino, Italy) and Professor Graham Jackson (NCCC, Newcastle Hospitals Trust, UK) whether MRD measurement is ready for clinical use
Role of minimal residual disease in treatment tailoring divides experts
by Thomas R. Collins
Minimal residual disease (MRD) is a guide for tailoring multiple myeloma whose time has come for wider exploration, an expert said here at the 57th Annual Meeting of the American Society of Haematology. Another expert, though, said that while the presence of minimal residual disease can predict outcome, it is not a marker of a cure and that its use must be handled carefully.
Bruno Paiva, PhD, an expert on MRD assessment at the University of Navarra in Spain, said that Next Generation Flow technology is ready to be woven more deeply into the fabric of clinical trials to help answer important questions about treatment durations in asymptomatic disease.
With the data on the matter clear, Dr. Paiva said he agrees that — viewed broadly — continuous therapy in smoldering multiple myeloma patients improves outcomes compared to fixed-duration therapy.1 But he said that the newest technology should be aggressively used to explore the nuances of treatment.
“Do all patients need continuous therapy to reach long-term survival? In other words, are some patients being under- or overtreated?” Dr. Paiva said. “I believe that the best approach to answer these questions is by implementing serial MRD in clinical trials using next generation MRD assays.”
In such trials, he suggested, after a period of maintenance, both those with MRD and without MRD should be randomized to receive either continuous maintenance therapy until progression or no maintenance therapy. Serial monitoring should be done to track the MRD of patients.
Antonio Palumbo, MD, Chief of the Myeloma Unit in the Department of Oncology at the University of Torino in Italy, said that once the results of such trials are in, clinicians will have their answer about the value of MRD in tailoring treatment, but not before.
“We do need study to decide whether MRD can be used to change treatment decisions,” he said.
It might be tempting to put a lot of faith into MRD status, but such an approach might be a mistake, he said. Studies have shown that even those who are MRD-negative have a progression-free-survival rate of just 60% at 7 years and just 25% at 10 years.
“MRD is not a biomarker for a cure,” Dr. Palumbo said.
He stressed the continued importance of imaging when making treatment decisions, noting that it’s been found that CT/PET is still positive in about 30% of patients in complete remission.2
Even with the high degree of sensitivity of Next Generation sequencing — detecting disease levels as minute as 10-6 — it is not the same as no disease, he said.
It’s important to remember the importance of the peripheral blood test, for closer monitoring. These more frequent tests prevent a situation in which several months pass before relapse is detected, if only Next Gen sequencing is used, he said.
“This is critical,” Dr. Palumbo said, “especially for the evaluation of relapse.”
There also needs to be a refining of the MRD scale — for instance, what constitutes a significant change in the level of disease found. Clinicians, he said, need more than just a positive or negative status.
“This,” he said, “is not real life.”
References
- Korde N, Roschewski M, Zingone A, et al. Treatment With Carfilzomib-Lenalidomide-Dexamethasone With Lenalidomide Extension in Patients With Smoldering or Newly Diagnosed Multiple Myeloma. JAMA Oncol. 2015 Sep;1(6):746-54.
- Zamagni E, Cavo M. The role of imaging techniques in the management of multiple myeloma. Br J Haematol. 2012 Dec;159(5):499-513.
