MM is a blood cancer originating in the bone marrow’s plasma cells. These cancerous cells multiply uncontrollably, crowding out healthy blood cells and producing monoclonal protein (M-protein). Treatment aims to reduce this burden of malignant cells. Achieving remission, the reduction or disappearance of disease signs and symptoms, is the primary goal of initial therapy.
Defining Remission Status in Multiple Myeloma
Remission is a tiered system based on the measurable reduction of disease markers, established by the International Myeloma Working Group (IMWG). The lowest level is a Partial Response (PR), achieved with at least a fifty percent reduction in serum M-protein and a similar decrease in bone marrow plasma cells.
A deeper response is the Very Good Partial Response (VGPR), requiring a ninety percent reduction in serum M-protein or reduction to a level only detectable by immunofixation. Complete Response (CR) is achieved when M-protein is undetectable in blood or urine, and a bone marrow biopsy shows less than five percent plasma cells. CR confirms the disappearance of any soft-tissue tumors (plasmacytomas) present at diagnosis.
The most profound level is the Stringent Complete Response (sCR), which adds specific laboratory requirements to CR criteria. Patients must have a normal ratio of free light chains and no evidence of clonal plasma cells in the bone marrow when tested by advanced techniques. Beyond sCR, Minimal Residual Disease (MRD) negativity means highly sensitive techniques cannot detect a single myeloma cell among 100,000 to 1,000,000 healthy cells. Achieving MRD negativity is associated with longer disease control.
Key Treatment Phases to Achieve Remission
Achieving remission follows a structured sequence of treatment phases. The initial phase is induction therapy, typically a triplet or quadruplet regimen. These regimens often include a proteasome inhibitor, an immunomodulatory drug (IMiD), and a corticosteroid. The goal of induction is to achieve a quick and substantial reduction in measurable disease markers.
Following induction, many eligible patients proceed to consolidation, often involving an autologous stem cell transplant (ASCT). This procedure uses high-dose chemotherapy to eliminate remaining myeloma cells, followed by an infusion of the patient’s own collected stem cells. ASCT aims to deepen the response, ideally moving a patient into CR or sCR status. Patients ineligible for ASCT may receive additional cycles of high-intensity therapy.
Modern treatments incorporate newer agents, such as monoclonal antibodies that target specific proteins on myeloma cells, into both induction and consolidation. These targeted therapies have significantly improved the rate and depth of remission. The specific drug combination is tailored to the individual patient, considering factors like age, overall health, and genetic markers.
Monitoring Disease Status During Remission
After achieving remission, the focus shifts to surveillance and maintenance therapy. Maintenance involves ongoing, low-dose treatment, often utilizing an IMiD (like lenalidomide) or a proteasome inhibitor. This therapy suppresses residual myeloma cells, preventing reactivation and helping sustain the deep response achieved during intensive phases.
Routine monitoring tracks disease markers using blood and urine tests. Serum protein electrophoresis checks for the M-spike (the signature of monoclonal protein). The serum free light chain assay monitors light chain levels and ratios, providing a sensitive measure of residual disease activity. These blood tests are typically performed monthly or every few months, depending on remission stability.
Imaging studies and bone marrow biopsies are also used periodically, though less frequently than blood tests. Bone marrow sampling confirms complete response or tests for MRD negativity, especially when considering changes to the maintenance regimen. PET-CT scans may be used to evaluate bone health and check for new soft-tissue plasmacytomas.
Understanding Relapse and Subsequent Treatment
Multiple myeloma is characterized by the likelihood of eventual relapse. Relapse is typically first detected biochemically, such as a twenty-five percent or greater increase in M-protein or free light chains from the lowest point reached during remission. This signals the re-emergence of the malignant plasma cell clone, often before physical symptoms appear.
A clinical relapse occurs when the increase in disease markers is accompanied by new or worsening symptoms (e.g., bone lesions, kidney dysfunction, or anemia). Treatment depends on the duration of the initial remission and previous therapies. If remission was prolonged, physicians may re-use the original successful drug combination. If relapse occurs quickly or during maintenance, the myeloma is considered resistant, necessitating a change in strategy. Subsequent “salvage” regimens introduce new classes of drugs or novel combinations. The goal remains achieving the deepest possible response and prolonging the next remission period.