Newly diagnosed multiple myeloma (NDMM) is a form of blood cancer that begins in the plasma cells, a type of white blood cell, located within the bone marrow. These abnormal plasma cells multiply uncontrollably, crowding out healthy blood-forming cells. The term “newly diagnosed” refers to patients who have recently received this diagnosis and are initiating their initial course of treatment.
Understanding Newly Diagnosed Multiple Myeloma
Multiple myeloma originates from plasma cells, which are specialized white blood cells normally responsible for producing antibodies to fight infections. In multiple myeloma, these plasma cells become cancerous and proliferate excessively in the bone marrow, the soft, spongy tissue. This uncontrolled growth interferes with the production of healthy red blood cells, white blood cells, and platelets, which are all essential for proper bodily function.
The accumulation of abnormal plasma cells and their defective antibodies, known as M-proteins, leads to several clinical features defining symptomatic multiple myeloma. These symptoms are often summarized by the acronym CRAB: C for hyperCalcemia (high calcium levels), R for Renal failure (kidney problems), A for Anemia (low red blood cell count), and B for Bone lesions or pain. Hypercalcemia occurs because myeloma cells activate cells that break down bone, releasing excess calcium into the bloodstream.
Kidney damage results from the buildup of M-proteins, which can clog the kidneys’ filtration system. Anemia develops when cancerous plasma cells crowd out healthy red blood cells in the bone marrow. Bone lesions, such as weakened spots or fractures, occur because myeloma cells disrupt the balance between bone breakdown and new bone formation, leading to pain.
Differentiating newly diagnosed multiple myeloma from precursor conditions like smoldering multiple myeloma (SMM) or monoclonal gammopathy of undetermined significance (MGUS) is important. While SMM and MGUS involve abnormal plasma cells or M-proteins, they do not present with the overt symptoms or organ damage seen in active multiple myeloma. The presence of CRAB features or other specific biomarkers indicates active disease requiring treatment.
Diagnosing Newly Diagnosed Multiple Myeloma
The diagnostic process for newly diagnosed multiple myeloma begins when a patient presents with symptoms that might suggest the condition, such as persistent bone pain, unexplained fatigue, or kidney issues. A healthcare provider will initiate a series of tests to investigate these concerns and confirm a diagnosis.
Blood tests are a primary component of the diagnostic workup. A complete blood count (CBC) helps identify anemia or other blood cell abnormalities. Serum protein electrophoresis (SPEP) and immunofixation electrophoresis (SIFE) detect and characterize the abnormal M-protein in the blood. A serum free light chain (FLC) assay measures the levels of light chain proteins to assess the presence of defective proteins.
Urine tests, including protein electrophoresis (UPEP) and immunofixation electrophoresis (UIFE), detect M-proteins that may be excreted in the urine. High levels of these proteins can indicate more extensive disease and contribute to kidney damage. Routine urinalysis also assesses kidney function.
Imaging studies are essential for evaluating bone health and detecting lesions. A skeletal survey helps identify bone damage. More advanced imaging techniques, such as magnetic resonance imaging (MRI) or positron emission tomography/computed tomography (PET/CT) scans, provide detailed views of bone lesions.
A bone marrow biopsy and aspiration are performed to confirm the diagnosis and assess plasma cell involvement. A small sample of bone marrow is taken to examine the percentage of abnormal plasma cells. A level exceeding 10% clonal plasma cells in the bone marrow confirms a diagnosis. The International Myeloma Working Group (IMWG) criteria serve as the standard guidelines for diagnosis, incorporating the presence of CRAB features and specific biomarkers.
Treatment Strategies for Newly Diagnosed Multiple Myeloma
Treatment for newly diagnosed multiple myeloma aims to reduce the tumor burden, achieve remission, improve quality of life, and extend survival. The approach involves multiple phases, tailored to the individual patient’s health and disease characteristics.
Induction therapy is the initial phase of treatment, designed to rapidly reduce the number of myeloma cells. Common drug classes utilized in induction regimens include proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and monoclonal antibodies, often combined with corticosteroids like dexamethasone. Proteasome inhibitors, such as bortezomib and carfilzomib, work by blocking the recycling of proteins within cancer cells, leading to their death. Immunomodulatory drugs like lenalidomide enhance the immune system’s ability to attack cancer cells. Monoclonal antibodies, such as daratumumab, target specific proteins like CD38 on myeloma cells, facilitating their destruction by the immune system.
Several combination regimens are widely used. Regimens like D-VRd, KRd, and RVd have shown to significantly improve outcomes. These multi-drug combinations aim to achieve a deep and sustained reduction in myeloma cells.
For eligible patients, autologous stem cell transplantation (ASCT) is a standard part of initial treatment. ASCT involves collecting the patient’s own healthy blood-forming stem cells before administering high-dose chemotherapy to destroy remaining cancer cells in the bone marrow. After chemotherapy, the previously collected stem cells are re-infused into the patient to help regenerate healthy blood cells. This procedure can lead to a deeper and more durable treatment response, extending progression-free survival.
Following ASCT, some patients may receive consolidation therapy, which involves a short course of treatment, typically 2 to 4 cycles, often with the same drugs used in induction. The purpose of consolidation is to deepen the response achieved from initial therapy and ASCT, aiming for a more complete remission.
Maintenance therapy is a long-term treatment phase that follows induction and, if applicable, ASCT and consolidation. This phase involves lower doses of medication, designed to prevent relapse and sustain remission over an extended period. Maintenance therapy aims to prolong progression-free survival and overall survival.
Managing Newly Diagnosed Multiple Myeloma Long-Term
Long-term management of newly diagnosed multiple myeloma extends beyond initial intensive treatment, focusing on ongoing monitoring, supportive care, and maintaining quality of life. Regular monitoring is essential to detect any signs of minimal residual disease (MRD) or potential relapse. This involves periodic blood tests to check for M-protein levels and other disease markers, along with imaging studies to assess bone health and identify any new lesions. MRD testing, which quantifies the remaining cancer cells after treatment, helps determine the depth of response.
Supportive care measures are integral to managing treatment-related side effects and preventing complications. Bone health management is a primary concern, as myeloma can cause significant bone damage. Bisphosphonates, such as zoledronic acid, and RANK ligand inhibitors like denosumab, are administered to reduce skeletal-related events, prevent fractures, and manage hypercalcemia by inhibiting bone breakdown.
Infection prevention is another important aspect, as patients with multiple myeloma often have compromised immune systems due to the disease and its treatments. Prophylactic antibiotics, such as trimethoprim-sulfamethoxazole or levofloxacin, may be prescribed to reduce the risk of bacterial infections. Vaccinations are also recommended to bolster the immune system.
Pain management is addressed through a multidisciplinary approach, utilizing analgesics, and in some cases, localized radiotherapy or surgical procedures for vertebral fractures. Managing other treatment-related side effects involves a combination of pharmacological and non-pharmacological interventions. A multidisciplinary care team, including various specialists, collaborates to provide comprehensive care. Emotional and psychological support are also important components of long-term management, addressing the challenges of living with a chronic condition.