Using New Modalities
There is no clear consensus about when to use each test, whether as part of the initial work-up, during follow-up, or upon progression, Dr Vij said. “The first test is WBXR or WBLDCT, whichever you have access to,” he said. The next step is less clear. “Then the question is, does everybody get a PET/CT for prognosis or should you reserve it for those patients with X-rays that are normal?” Dr Vij said. He commented that the field is split on this issue because “it doesn’t really lead to any changes in treatment if the diagnosis of MM has already been established by other criteria.”
PET/CT use at the time of progression is also controversial. In most cases, M protein levels indicate progression. Some patients, however, are asymptomatic or do not show body or organ deterioration despite blood tests indicating progression. “In that scenario, PET scan is increasingly being done to adjudicate the need for treatment and the aggressiveness of the treatment,” Dr Vij said. He also noted that PET/CT is the only way to detect progression in more advanced disease, at which point M protein is no longer produced and therefore cannot be used to detect further progression.
Dr Vij said that the use and frequency of PET/CT during follow up of various plasma cell dyscrasias is still the subject of study, and the IMWG is currently developing guidelines to address questions in this area.
Agents for Bone Disease
There are 2 classes of agents available for the treatment of bone disease in MM: bisphosphates and an anti-RANKL antibody. These agents inhibit osteoclast activity, thereby preventing new osteolytic lesions, pathologic fractures, and hypercalcemia.
The RANKL inhibitor denosumab was shown to be noninferior to the bisphosphonate zoledronic acid, with similar rates of skeletal-related events and overall survival. Osteonecrosis of the jaw occurred at similar rates between groups.1 Progression-free survival (PFS), however, was prolonged by over 10 months with denosumab (compared with those receiving zoledronate), raising the question of whether denosumab may have an anticancer effect. Dr Vij pointed out, however, that PFS “was not the primary endpoint of the study,” and this PFS advantage has not made denosumab a preferred agent in the guidelines.
Selection between bisphosphonates and denosumab comes down to cost and renal disease. Bisphosphonate are “literally a tenth of the cost of denosumab, but denosumab has little in the way of renal side effects,” Dr Vij said. This is important given that many patients with MM have renal dysfunction at diagnosis or develop it as their disease progresses. For these patients, “denosumab is certainly the best option,” he said, “but to give it to everybody, is certainly not something that most physicians or opinion leaders currently recommend because of the cost.”
Ongoing research is expected to further improve imaging for bone disease in MM. Dr Vij highlighted a novel MR technique called diffusion-weighted MRI, which “provides a functional aspect to MRI in addition to the structural and anatomical aspects.” He also described novel tracers to improve PET/CT.
“The other area where I think research is focused is the utility of MRI and especially PET/CT in the follow-up of patients with MM and other plasma cell dyscrasias,” Dr Vij said.
- Zamagni E, Cavo M, Fakhri B et al. Bones in multiple myeloma: Imaging and therapy. Am Soc Clin Oncol Educ Book. 2018;38:638-646. doi: 10.1200/EDBK_205583