Multiple myeloma is a cancer affecting plasma cells, a type of white blood cell found in the bone marrow. Abnormal plasma cells multiply uncontrollably, crowding out healthy blood cells and potentially causing various health complications. First-line treatment refers to the initial therapy given to a patient immediately following a diagnosis of active multiple myeloma. This treatment aims to reduce myeloma cells and improve a patient’s overall health.
Understanding Initial Treatment Goals
The primary objectives of first-line multiple myeloma treatment are to achieve remission, alleviate symptoms, and enhance a patient’s quality of life. Remission indicates a significant reduction or absence of active myeloma, ranging from partial to complete. Treatment also aims to prevent complications such as kidney failure, high blood calcium, or bone damage.
Initial treatment selection is influenced by several patient- and disease-specific factors. A patient’s age and overall health play a significant role in determining treatment intensity. Disease characteristics, including genetic markers and myeloma stage, guide decisions. Patient preferences, such as administration route (oral versus intravenous) and potential side effects, are also considered to tailor the most appropriate plan.
Standard Treatment Regimens
First-line treatment for multiple myeloma involves combinations of different drug classes. These multi-drug regimens, often with three or four agents, target myeloma cells through various mechanisms to achieve the deepest and most durable response.
Proteasome Inhibitors
Proteasome inhibitors, such as bortezomib (Velcade), carfilzomib (Kyprolis), and ixazomib (Ninlaro), disrupt the proteasome, a cellular structure breaking down proteins. Inhibiting this process causes protein accumulation within myeloma cells, leading to their death. Bortezomib is often administered by subcutaneous injection, carfilzomib intravenously, and ixazomib is an oral option.
Immunomodulatory Drugs (IMiDs)
Immunomodulatory drugs (IMiDs), including lenalidomide (Revlimid), pomalidomide (Pomalyst), and thalidomide, interact with myeloma cells and their environment. They influence the immune system and directly affect cancer cell growth. Lenalidomide is frequently used and taken orally.
Corticosteroids
Corticosteroids, such as dexamethasone, are commonly included in regimens. Dexamethasone has direct anti-myeloma effects and helps manage certain treatment side effects. It is often used with proteasome inhibitors and IMiDs.
Monoclonal Antibodies
Monoclonal antibodies, like daratumumab (Darzalex) and isatuximab (Sarclisa), specifically target proteins on myeloma cell surfaces, such as CD38. By binding, they trigger the immune system to destroy cancer cells. Daratumumab can be given via subcutaneous injection, while others are administered intravenously.
Common first-line combinations for transplant-eligible patients include a proteasome inhibitor, an IMiD, and a steroid, sometimes with a monoclonal antibody. An example is daratumumab in combination with bortezomib, lenalidomide, and dexamethasone (Dara-VRd).
The Role of Autologous Stem Cell Transplant
An autologous stem cell transplant (ASCT) is a procedure where a patient’s own healthy blood-forming stem cells are collected and reinfused after high-dose chemotherapy. This approach is for younger, fitter patients who are “transplant-eligible,” meaning under 70 years of age with adequate organ function.
The purpose of ASCT in first-line treatment is to achieve a deeper, more durable remission by intensifying anti-myeloma therapy. The process begins with stem cell collection from the patient’s circulating blood. These collected cells are frozen for later use. Following collection, the patient receives high-dose chemotherapy, commonly with melphalan, to eliminate myeloma cells. After chemotherapy, thawed stem cells are reinfused, restoring the bone marrow’s ability to produce healthy blood cells and aiding recovery.
Monitoring and Managing Treatment
During and after first-line treatment, doctors closely monitor the patient’s response to therapy and manage any side effects. Monitoring methods include regular blood tests, which track markers like M protein and free light chains, and bone marrow biopsies to assess the presence of myeloma cells. Imaging studies, such as PET/CT or MRI, may also be used to identify bone lesions or other signs of disease activity. The goal is to determine how effectively the treatment is reducing the myeloma burden.
Patients may experience various side effects from the treatments, such as fatigue, low blood counts (anemia, neutropenia, thrombocytopenia), nausea, vomiting, and peripheral neuropathy. Management strategies involve supportive care, including medications to alleviate symptoms like nausea, and dose adjustments of the anti-myeloma drugs as needed. For instance, if peripheral neuropathy develops with bortezomib, the dose may be reduced to prevent worsening symptoms.
After the initial phase of treatment, patients may transition to maintenance therapy. This involves continuing a lower dose of a specific drug, such as lenalidomide, to prolong the remission achieved with the first-line therapy. Maintenance therapy aims to keep the myeloma under control for an extended period, potentially for two years or longer, to delay disease progression.