Dr. Jewell is a hematology/oncology fellow, Dr. Xiang, Dr. Kunthur, and Dr. Mehta are staff hematologist/oncologists, all in the Division of Hematology/Oncology, Department of Internal Medicine, at the John L. McClellan Memorial Veterans Hospital in Little Rock, Arkansas. Dr. Xiang and Dr. Mehta are also faculty members at the University of Arkansas for Medical Sciences in Little Rock.
References
All myeloma patients are risk stratified at initial diagnosis based on their cytogenetic abnormalities identified mainly by FISH studies and conventional cytogenetics, which can serve as an alternative if FISH is unavailable. Genetic abnormalities of MM are the major predictor for the outcome and will affect treatment choice. Three risk groups have been identified: high-risk, intermediate-risk, and standard-risk MM (Table 4). 11
Management of MGUS and SMM
Patients with MGUS progress to malignant conditions at a rate of 1% per year. 12 Those individuals who are diagnosed with MGUS or SMM typically do not require therapy. According to the International Myeloma Working Group guidelines, patients should be monitored based on risk stratification. Those with low-risk MGUS (IgG M protein < 1.5 g/dL and no abnormal FLC ratio) can be monitored every 6 months for 2 to 3 years. Those who are intermediate to high risk need a baseline bone marrow biopsy in addition to skeletal survey and should check urine and serum levels for protein every 6 months for the first year and then annually thereafter.
Patients with SMM are at an increased risk of progression to symptomatic MM compared with patients with MGUS (10% per year for the first 5 years, 3% per year for the next 5 years). 13 Therefore, experts recommend physician visits and laboratory testing for M proteins every 2 to 3 months for the first year and then an evaluation every 6 to 12 months if the patient remains clinically stable. 14 Additionally, there are new data to suggest that early therapy with lenalidomide plus dexamethasone for SMM can prolong time to disease progression as well as increase OS in individuals with SMM at high risk for progression. 15
Patients With MM
All patients with a diagnosis of MM require immediate treatment. Initial choice of therapy is driven by whether a patient is eligible for an autologous stem cell transplant (ASCT), because certain agents, such as alkylating agents, should typically be avoided in those who are transplant eligible. Initial therapy for patients with MM is also based on genetic risk stratification of the disease. Patients with high-risk disease require a complete response (CR) treatment for long-term OS and thus benefit from an aggressive treatment strategy. Standard-risk patients have similar OS regardless of whether or not CR is achieved and thus can either be treated with an aggressive approach or a sequential therapy approach. 16
Transplant-Eligible Patients
All patients should be evaluated for transplant eligibility, because it results in superior progression-free survival (PFS) and OS in patients with MM compared with standard chemotherapy. Transplant eligibility requirements differ, depending on the transplant center. There is no strict age limit in the U.S. for determining transplant eligibility. Physiological age and factors such as functional status and liver function are often considered before making a transplant decision.
For VA patients, transplants are generally considered in those aged < 65 years, and patients are referred to 1 of 3 transplant centers: VA Puget Sound Healthcare System in Seattle, Washington; Tennessee Valley Healthcare System in Nashville; or South Texas Veterans Healthcare System in San Antonio. 17 All patients who are transplant eligible should receive induction therapy for 2 to 4 months before stem cell collection. This is to reduce tumor burden, for symptomatic management, as well as to lessen end organ damage. After stem cell collection, patients undergo either upfront ASCT or resume induction therapy and undergo a transplant after first relapse.
