The most successful treatment for multiple myeloma (MM) is an individualized, multi-stage therapeutic sequence, not a single drug. MM is a cancer of the plasma cells, a type of white blood cell, which accumulate abnormally in the bone marrow. These malignant cells can damage bone, cause kidney problems, and suppress normal blood cell production. Treatment involves a strategic plan of sequential therapies designed to achieve the deepest possible remission, representing the current standard for long-term disease management.
Determining the Individualized Treatment Pathway
The initial treatment plan is determined by a comprehensive assessment of disease characteristics and patient health. Success is measured by the reduction of cancer cells, durable progression-free survival (PFS), and overall survival (OS). The goal is to maximize the depth and duration of remission while maintaining a high quality of life.
A primary factor is patient eligibility for intensive therapy, specifically high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Eligibility is based on age, performance status (a measure of daily functioning), and the presence of co-morbidities like heart or kidney issues. Patients considered “fit” or “transplant-eligible” generally receive a more intensive frontline regimen that includes ASCT.
Disease-specific risk stratification plays an equally significant role. Oncologists use genetic testing to identify high-risk multiple myeloma. The presence of certain chromosomal abnormalities, such as deletion of chromosome 17p or the translocation t(4;14), indicates a more aggressive disease requiring a highly potent initial regimen, often a four-drug combination.
Core Stages of Initial Therapy
The standard of care follows a well-defined sequence of phases designed to eliminate myeloma cells. This process begins with induction therapy, the initial treatment course aimed at rapidly reducing the tumor burden. Induction typically involves a combination of three or four drugs administered over several months to achieve a strong initial response.
Following induction, the treatment moves to a consolidation phase, which often involves ASCT for eligible patients. ASCT uses high-dose chemotherapy to destroy remaining cancer cells, followed by the re-infusion of the patient’s own collected stem cells to rescue the bone marrow. This procedure is a powerful consolidation step, associated with deeper responses and longer progression-free survival. Patients not candidates for ASCT may receive additional cycles of induction therapy as consolidation.
The final, long-term phase is maintenance therapy, a continuous, low-dose treatment administered indefinitely until the disease progresses or side effects become intolerable. The primary goal of maintenance is to sustain the deep remission achieved earlier and prevent relapse. A common maintenance agent is the immunomodulatory drug lenalidomide, though high-risk patients may receive a combination of drugs.
Essential Drug Classes and Their Roles
Modern multiple myeloma treatment relies on combining agents from different drug classes, each attacking cancer cells through a unique mechanism. One class is the Proteasome Inhibitors (PIs), which block the proteasome, a cellular complex responsible for breaking down damaged proteins. By preventing this breakdown, PIs cause toxic proteins to accumulate inside the plasma cells, leading to their programmed death. Common PIs include bortezomib and carfilzomib, which are used in many induction regimens.
Another essential class is the Immunomodulatory Drugs (IMiDs), such as lenalidomide and pomalidomide. These agents work by binding to the protein cereblon, triggering the degradation of specific proteins required for myeloma cell survival. IMiDs also stimulate the patient’s immune system, enhancing the activity of natural killer (NK) and T-cells to attack the cancer.
More recently, Monoclonal Antibodies (mAbs) have become indispensable, particularly those targeting the CD38 protein found on the surface of most myeloma cells (e.g., daratumumab and isatuximab). These antibodies attach directly to the cancer cell and recruit the body’s immune defenses, including NK cells and macrophages, to destroy the flagged cells. This process is called antibody-dependent cell-mediated cytotoxicity (ADCC). The combination of PIs, IMiDs, and mAbs has significantly improved initial response rates and long-term outcomes.
Treatment for Relapsed and Refractory Myeloma
Despite effective initial therapy, multiple myeloma is characterized by relapse, where the cancer returns and often becomes resistant to previous treatments. When the disease is defined as relapsed and refractory (R/R)—progressed despite current therapy—oncologists use newer, highly potent immunotherapies. These therapies often target B-cell Maturation Antigen (BCMA), a protein heavily expressed on myeloma cells.
One successful option for R/R disease is Chimeric Antigen Receptor (CAR) T-cell therapy. This involves genetically modifying a patient’s own T-cells to recognize and attack BCMA-expressing myeloma cells. CAR T-cell therapy, such as ciltacabtagene autoleucel (cilta-cel), has demonstrated high efficacy, achieving overall response rates approaching 98% in some trials. This therapy offers deep and durable remissions but is a complex, one-time treatment requiring specialized centers.
A less intensive but highly effective alternative is the use of Bispecific Antibodies, which are “off-the-shelf” drugs administered more readily. These antibodies, such as teclistamab, simultaneously bind to a T-cell and the BCMA protein on a myeloma cell, physically bridging the two cells. This action redirects the patient’s immune system to destroy the cancer, providing high response rates, often exceeding 60%.