Understanding the Different
Phases of Treatment FOR MULTIPLE MYELOMA
Multiple myeloma (MM) is caused by clonal plasma cell growth, primarily in bone marrow, resulting in bone destruction, renal insufficiency, anemia, and hypercalcemia. MM accounts for 1% of all cancers and 10% of all hematological cancers in the United States.1 An estimated 30,000 new cases will be diagnosed in 20172 at a median patient age of 69 years, with most frequent diagnoses between ages 65 and 74.2
Between 2004 and 2013, new myeloma cases increased on average 0.8% per year; however, as a result of novel and more effective treatments, death rates have declined at the same average rate.2 An estimated 95,688 Americans in 2013 were living with MM, with a 5-year survival rate of 48.5%.1 Because MM is an incurable disease, treatment is an ongoing process.3
Initial treatment of MM differs for transplant-eligible and non-eligible patients. Transplant-eligible patients typically receive four to six cycles of induction therapy before stem cell collection and/or transplant (SCT), with response assessment after one to two cycles of therapy.2 The National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology2 and other clinical practice guidelines recommend choosing a regimen consisting of some combination of a proteosome inhibitor (bortezomib, carfilzomib, ixasomib); an immunomodulatory drug (IMiD; lenalidomide, thalidomide); an alkylating agent (cyclophosphamide); and/or chemotherapy (doxorubicin) along with dexamethasone for primary therapy.
Maintenance therapy follows, with consolidation therapy considered in some patients. The goal of maintenance therapy is achieving a longer progression-free survival (PFS) and overall survival (OS).4 Options for maintenance therapy include lenalidomide or bortezomib.2 Although lenalidomide maintenance improves survival, some studies show that lenalidomide can cause second malignancy during maintenance therapy, possibly when preceded closely by an alkylator-based therapy (eg, in a SCT patient).5 Bortezomib is well-tolerated and shows good response rates, and is not associated with a risk of secondary malignancies.2 Thus, it can be used instead of lenalidomide in cases with high-risk cytogenic markers or in some cases of advanced renal insufficiency.2
One of the controversies in MM therapy is the duration of maintenance treatment. The goal of extending remission must be balanced with the toxicity, tolerability, convenience, and cost associated with possibly treating a patient until progression.4 Capping lenalidomide maintenance therapy at 2 years for patients who achieve a sustained complete response can be considered; however, prospective data is lacking for this approach.5 Some clinical trials are currently underway to look at a longer maintenance period as well as other drug combinations.4 In addition to toxicity, there is concern over the economics of treating a patient indefinitely with costly maintenance therapy.
The biggest challenge of MM treatment comes when patients relapse after previous therapy. “Most people in the myeloma field are comfortable with what they’re recommending for upfront therapy. It’s when relapses happen that there’s a lot of choices, and it takes thought about what you’re trying to accomplish,” said Natalie S Callander, MD, a hematology/bone marrow transplant specialist at the University of Wisconsin School of Medicine and Public Health (Madison, WI).