MRI FOR MM

The International Myeloma Working Group (IMWG) has issued practical recommendations on the use of MRI in patients with multiple myeloma (MM) and in patients with asymptomatic disease, such smoldering MM and monoclonal gammopathy of undetermined significance (MGUS).

The consensus statement was  published online January 20 in the Journal of Clinical Oncology

These are practice changing for patients with smoldering MM. In this group of patients, "these recommendations affect therapeutic decision making," writes Morie A. Gertz, MD, from the College of Medicine in Rochester, Minnesota, in an accompanying editorial.

This sentiment was echoed by IMWG member Meletios A. Dimopoulos, MD, from the Department of Clinical Therapeutics, National and Kapodistrian University of Athens School of Medicine, Alexandra General Hospital, Athens, Greece.

"Patients who have more than one focal lesion in the MRI are now considered to have symptomatic disease that needs treatment. Therefore, this paper changes clinical practice," Dr Dimopoulos told Medscape Medical News.

Until now, patients with asymptomatic disease were typically followed with observation and treated on disease progression. Disease was considered asymptomatic if the CRAB criteria (C for hypercalcemia, R for renal failure, A for anemia, B for bone disease) indicated no evidence of organ damage.

In the past. bone disease was identified with whole-body x-ray (WBXR). But MRI is more sensitive than WBXR for determining bone involvement, Dr Dimopoulos and colleagues point out, and the updated recommendations introduce novel MRI criteria for defining smoldering MM.

Recent research has shown that risk for progression at 2 years is more than 70% in patients with asymptomatic myeloma who meet the CRAB criteria and who have more than one focal lesion on MRI. Therefore, all members of the IMWG agree that such patients need antimyeloma therapy," Dr Dimopoulos told Medscape Medical News.

MRI Improves Clinical Management of Patients

"The use of advanced skeletal imaging is certain to improve the management of patients with asymptomatic multiple myeloma," writes Dr Gertz, "because it refines the understanding of their disease. It is prognostic in multiple myeloma and may have value in patients with higher-risk MGUS."

When whole-body MRI is not available, "a spine and pelvic MRI could identify almost 90% of the focal lesions of the patient. If MRI technology is not available at all, bone involvement can be evaluated by other imaging techniques, such as whole-body low-dose [WBLD] CT or PET/CT (which is more expensive)," Dr Dimopoulos explained.

However, he stressed, "MRI reveals the bone marrow infiltration and not the presence of lytic lesions, whereas WBLD CT or PET/CT (the CT part) can reveal osteolytic lesions. Thus, in asymptomatic patients with normal skeletal radiography or normal WBLD CT, MRI provides significant information, as it drives the decision for giving therapy instead of observation."

The consensus statement updates previous IMWG recommendations (Leukemia.  2009;23:1545-1556).

IMWG Reviews Value of MRI

he updated recommendations were made on the basis of an analysis of published literature, including clinical and observational studies, meta-analyses, and systemic reviews.

The recommendations summarize whole-body, diffuse weighted imaging, dynamic contrast imaging, and PET MRI procedures. In addition, five patterns of marrow involvement are described: normal appearance of bone marrow; focal involvement of bone marrow (positive focal lesion ≥5 mm in diameter), seen in 18% to 50% of patients; homogeneous diffuse infiltration, seen in 25% to 43% of patients; combined diffuse and focal infiltration; and variegated (salt-and-pepper) pattern with inhomogeneous bone marrow and interposition of fat islands, seen in 1% to 5% of patients.

"Clinicians need to know the different MRI techniques and MRI patterns of marrow infiltration, and their value in the diagnosis, follow-up, and better definition of response in myeloma patients, as well as the MRI value in other plasma cell disorders (e.g., solitary plasmacytoma, MGUS, and asymptomatic myeloma)," Dr Dimopoulos explained.

Value of MRI in Smoldering MM 

In clinical practice, the presence of WBXR-identified lytic lesions in patients with smoldering MM indicate risk for early progression. Typically, such patients are treated, whereas patients with no lytic lesions are followed with observation.

The consensus statement notes that 20% to 50% of patients who show no lesions on WBXR show abnormal bone marrow on MRI. Research has shown that these patients are at higher risk for progression (hazard ratio, 4.05; P <.001) and have a longer treatment duration (16 vs 43 months) (J Clin Oncol.  2010;28:1606-1610). In that study, median time to progression was 13 to 15 months and the progression rate at 2 years was 70%.

Identifying these patients early is important because they could benefit from immediate therapy, the IMWG points out. In fact, in a controlled trial, the 3-year overall survival rate was better in patients who received early treatment than in those initially followed with observation (94% vs 80%) (N Engl J Med. 2013;369:438-447).

For smoldering MM, the consensus statement recommends "that patients with more than one unequivocal focal lesion (diameter of >5 mm) should be considered to have symptomatic myeloma that requires therapy (grade B). Patients with equivocal focal lesions should repeat the MRI after 3 to 6 months, and in cases of MRI progression, patients should be considered as symptomatic patients who need therapy (grade C; panel consensus). The biopsy of such lesions should be encouraged. Regarding diffuse MRI marrow pattern, we need additional studies before its incorporation into the definition of symptomatic myeloma."

For MGUS, the statement notes that "WB-MRI identifies patients with MGUS with focal lesions that possibly reflect infiltration by monoclonal plasma cells in the bone marrow. These patients seem to have increased risk of progression to myeloma. To date, MRI is not recommended as part of the routine workup for patients with MGUS unless there are clinical features that increase suspicion."

For MM, the statement explaines that "MRI is the imaging gold-standard method for the detection of bone marrow involvement in MM (grade A). We stress that MRI detects bone marrow involvement and not bone destruction. MRI of the spine and pelvis can detect approximately 90% of focal lesions in MM, and thus, it can be used in cases where WB-MRI is not available (grade B). MRI is the procedure of choice to evaluate a painful lesion in patients with myeloma, mainly in the axial skeleton, and detect spinal cord compression (grade  A). MRI is particularly useful in the evaluation of collapsed vertebrae, especially when myeloma is not active, where the possibility of osteoporotic fracture is high (grade B)."

Table. Summary of Recommendations on the Value of MRI

Recommendation	Grade*
Soldering MM
Patients with at least 1 unequivocal lesion (>5 mm) considered to have symptomatic MM and requiring therapy	yes
Patients with equivocal focal lesion should be monitored every 3 to 6 months; if progress is seen on MRI, therapy should be considered	maybe
MGUS
MRI recommended for routine workup	no
MM (partial list)
Gold standard for bone marrow involvement	yes
MRI of pelvis and spine can be used when whole-body MRI is not available	yes
MRI to determine painful lesions and spinal compression	yes
MRI determines MM from nonmalignant fractures	yes
Focal pattern provides prognostic information and diffuse pattern related to inferior prognosis	yes
MRI recommended for treatment follow-up	no
*Grade A and B recommendations are listed as yes, grade C as maybe.

Several members of the International Myeloma Working Group and Dr Gertz have reported ties to industry.

J Clin Oncol. Published online January 20, 2015.  Abstract