Multiple myeloma (MM) is a cancer of plasma cells, a type of white blood cell that produces antibodies. These cancerous cells accumulate in the bone marrow, crowding out healthy blood cells and causing complications. The “most successful treatment” is not a single procedure, but a carefully sequenced combination of therapies tailored to the patient’s age, health, and disease characteristics. Since MM is currently considered incurable, the primary goal is to achieve a deep and durable remission, maximizing the time a patient lives without the disease progressing. This comprehensive strategy involves distinct phases, starting with potent drug combinations to reduce the tumor burden, followed by consolidation and long-term maintenance.
Initial Treatment Strategies
The first phase of treatment is induction therapy, designed to rapidly decrease the number of myeloma cells. Success is measured by the depth of the initial response. Standard-of-care regimens use a combination of three or four different drug classes, known as triplet or quadruplet therapy.
These typically combine an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and a corticosteroid like dexamethasone. Common triplets include bortezomib, lenalidomide, and dexamethasone (VRd). Newer quadruplet approaches integrate a monoclonal antibody, such as an anti-CD38 agent like daratumumab, into the standard triplet backbone. This fourth agent aims to achieve a deeper initial response and higher rates of minimal residual disease (MRD) negativity, which is associated with better long-term outcomes.
The Role of Autologous Stem Cell Transplantation
For physically fit and typically younger patients, Autologous Stem Cell Transplantation (ASCT) is a foundational consolidation step following induction therapy. The procedure aims to deepen the remission achieved by the initial drug regimen. ASCT involves collecting the patient’s own healthy stem cells (harvesting).
The patient then receives high-dose chemotherapy, usually melphalan, which kills remaining myeloma cells but also destroys bone marrow cells. The collected stem cells are then reinfused (cell rescue) to restore the blood-forming system. This high-dose approach is the most potent method for eliminating residual disease and is strongly recommended for eligible, newly diagnosed patients. ASCT provides the best chance for a deep and long-lasting response, extending disease control compared to drug therapy alone.
Sustaining Remission with Maintenance Therapy
Once a deep response is achieved, patients transition to long-term, lower-intensity maintenance therapy. The goal is to suppress remaining cancer cells, preventing or significantly delaying relapse. Success is measured predominantly by Progression-Free Survival (PFS)—the length of time a patient lives without the disease worsening.
Lenalidomide is the most common maintenance agent, often taken continuously until the disease progresses. Clinical trials show that lenalidomide maintenance significantly improves PFS and extends overall survival, especially post-ASCT. For high-risk patients with specific genetic markers, a more intensive regimen, potentially combining lenalidomide with a proteasome inhibitor like bortezomib, may be used.
Breakthroughs in Relapsed or Refractory Disease
Multiple myeloma will eventually return or become resistant to treatment in most patients, known as relapsed or refractory disease. This area has seen dramatic recent breakthroughs with immune-harnessing cellular and antibody therapies.
CAR T-Cell Therapy
Chimeric Antigen Receptor (CAR) T-cell therapy involves collecting a patient’s T-cells, modifying them to recognize a specific protein on myeloma cells (like BCMA), and reinfusing them to destroy the cancer. CAR T-cell therapies have demonstrated impressive overall response rates (66% to 99%) in heavily pretreated patients, leading to deep and durable remissions.
Bispecific T-Cell Engagers (BiTEs)
Similarly, Bispecific T-cell Engagers (BiTEs), such as teclistamab, are highly successful. BiTEs are engineered antibodies that physically bridge a patient’s T-cell to the myeloma cell, activating the T-cell to kill the cancer directly. These therapies offer robust overall response rates, typically between 50% and 70%, and are revolutionizing the treatment of patients whose disease has failed multiple prior lines of therapy.