Treatment is indicated in<unk>  with symptoms. If there are no symptoms, but a paraprotein typical of<unk>  and diagnostic bone marrow is present without end-organ damage, treatment is usually deferred or restricted to clinical trials. Treatment for<unk>  is focused on decreasing the clonal plasma cell population and consequently decrease the symptoms of disease. Chemotherapy Initial Initial treatment of<unk>  depends on the person's age and other illnesses present. The preferred treatment for those under the age of 65 is high-dose chemotherapy, commonly with bortezomib-based regimens, and lenalidomide–dexamethasone, to be followed by a stem cell transplant. A 2016 study concluded that stem cell transplant is the preferred treatment of<unk> . There are two types of stem cell transplants to treat<unk> . In autologous hematopoietic stem-cell transplantation (ASCT) – the patient's own stem cells are collected from the patient's own blood. The patient is given high-dose chemotherapy, and the patient's stem cells are then transplanted back into the patient. The process is not curative, but does prolong overall survival and complete remission. In allogeneic stem-cell transplantation, a healthy donor's stem cells are transplanted into the affected person. Allogenic stem-cell transplantation has the potential for a cure, but is used in a very small percentage of people (and in the relapsed setting, not as part of initial treatment). Furthermore, a 5–10% treatment-associated mortality rate is associated with allogeneic stem-cell transplant. People over age 65 and people with significant concurrent illnesses often cannot tolerate stem-cell transplantation. For these people, the standard of care has been chemotherapy with melphalan and prednisone. Recent studies among this population suggest improved outcomes with new chemotherapy regimens, e.g., with bortezomib. Treatment with bortezomib, melphalan, and prednisone had an estimated overall survival of 83% at 30 months, lenalidomide plus low-dose dexamethasone an 82% survival at 2 years, and melphalan, prednisone, and lenalidomide had a 90% survival at 2 years. Head-to-head studies comparing these regimens have not been performed . There is support for continuous therapies with<unk>  drug combinations of antimyeloma drugs bortezomib, lenalidomide and thalidomide as initial treatment for transplant-ineligible<unk> . Further clinical studies are required to determine the potential harms of these drugs and the effect on the person's quality of life. A 2009 review noted, "Deep venous thrombosis and pulmonary embolism are the major side effects of thalidomide and lenalidomide. Lenalidomide causes more myelosuppression, and thalidomide causes more sedation. Chemotherapy-induced peripheral neuropathy and thrombocytopenia are major side effects of bortezomib." Treatment of related hyperviscosity syndrome may be required to prevent neurologic symptoms or kidney failure. Maintenance Most people, including those treated with ASCT, relapse after initial treatment. Maintenance therapy using a prolonged course of low-toxicity medications is often used to prevent relapse. A 2017 meta-analysis showed that post-ASCT maintenance therapy with lenalidomide improved progression-free survival and overall survival in people at standard risk. A 2012 clinical trial showed that people with intermediate- and high-risk disease benefit from a bortezomib-based maintenance regimen. Relapse Reasons for relapse include disease evolution, either from the selective pressure applied by treatment or by de novo mutations and/or if disease was inadequately represented in the initial biopsy. Relapse within the first 18 months of diagnosis is considered as functional high risk<unk> . Depending on the person's condition, the prior treatment modalities used and the duration of remission, options for relapsed disease include retreatment with the original agent, use of other agents (such as melphalan, cyclophosphamide, thalidomide, or dexamethasone, alone or in combination), and a second ASCT. Later in the course of the disease, it becomes refractory (resistant) to formerly effective treatment. This stage is referred to as relapsed/refractory<unk>  (RRMM). Treatment modalities that are commonly use to treat RRMM include dexamethasone, proteasome inhibitors (e.g. bortezomib and carfilzomib), immunomodulatory imide drugs (e.g. thalidomide, lenalidomide, and pomalidomide), and certain monoclonal antibodies (e.g. against CD38 and CD319). Survival expectancy has risen in recent years, and new treatments are under development. Kidney failure in<unk>  can be acute (reversible) or chronic (irreversible). Acute kidney failure typically resolves when the calcium and paraprotein levels are brought under control. Treatment of chronic kidney failure is dependent on the type of kidney failure and may involve dialysis. Several newer options are approved for the management of advanced disease: * belantamab mafodotin — a monoclonal antibody against B-cell maturation antigen (BCMA), also known as CD269, indicated for the treatment of adults with relapsed or refractory<unk>  who have received at least four prior therapies including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory agent. * carfilzomib—a proteasome inhibitor that is indicated: * as a single agent in people who have received one or more lines of therapy * in combination with dexamethasone or with lenalidomide and dexamethasone in people who have received one to three lines of therapy * daratumumab—a monoclonal antibody against CD38 indicated in people who have received at least three prior lines of therapy including a proteasome inhibitor and an immunomodulatory agent or who are double refractory to a proteasome inhibitor and an immunomodulatory agent * elotuzumab—an immunostimulatory humanized monoclonal antibody against SLAMF7 (also known as CD319) indicated in combination with lenalidomide and dexamethasone in people who have received one to three prior therapies * isatuximab—a monoclonal antibody against CD38 indicated in combination with pomalidomide and dexamethasone for the treatment of adults with<unk>  who have received at least two prior therapies including lenalidomide and a proteasome inhibitor. * ixazomib—an orally available proteasome inhibitor indicated in combination with lenalidomide and dexamethasone in people who have received at least one prior therapy * panobinostat—an orally available histone deacetylase inhibitor used in combination with bortezomib and dexamethasone in people who have received at least two prior chemotherapy regimens, including bortezomib and an immunomodulatory agent * selinexor—an orally available selective inhibitor of nuclear export indicated in combination with dexamethasone in people who have received at least four prior therapies and whose disease does not respond to at least two proteasome inhibitors, two immunomodulatory agents and an anti-CD38 monoclonal antibody * idecabtagene vicleucel—first cell-based gene therapy was approved by FDA in 2021 for the treatment of adults with relapsed or refractory<unk>  who have received at least four prior therapies Stem cell transplant Stem cell transplant can be used to treat<unk> . Stem cell transplants come with a risk of a graft-versus-host-disease. Mesenchymal stromal cells may reduce the all-cause mortality if they are used for a therapeutic reason and the therapeutic use of MSCs may increase the complete response of acute and chronic GvHD, but the evidence is very uncertain. The evidence suggests that MSCs for prophylactic reason result in little to no difference in the all-cause mortality, in the relapse of malignant diseases and in the incidence of acute GvHD. The evidence suggests that MSCs for prophylactic reason reduce the incidence of chronic GvHD. Gene therapy Ciltacabtagene autoleucel (Carvykti) was approved for medical use in the United States in February 2022. Ciltacabtagene autoleucel is indicated for the treatment of adults with relapsed or refractory<unk>  after four or more prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Other measures In addition to direct treatment of the plasma cell proliferation, bisphosphonates (e.g., pamidronate or zoledronic acid) are routinely administered to prevent fractures; they have also been observed to have a direct antitumor effect even in people without known skeletal disease. If needed, red blood cell transfusions or erythropoietin can be used for management of anemia. Side effects Chemotherapies and stem cell transplants can cause unwanted bleedings and may require platelet transfusions. It was seen that platelet transfusions for people undergoing a chemotherapy or a stem cell transplantation for the prevention of bleeding events had different effects on the number of participants with a bleeding event, the number of days on which a bleeding occurred, the mortality secondary to bleeding and the number of platelet transfusions depending on the way they were used (therapeutic, depending on a threshold, different dose schedules or prophylactic). Supportive treatment Adding physical exercises to the standard treatment for adult patients with haematological malignancies like<unk>  may result in little to no difference in the mortality, in the quality of life and in the physical functioning. These exercises may result in a slight reduction in depression. Furthermore, aerobic physical exercises probably reduce fatigue. The evidence is very uncertain about the effect and serious adverse events Palliative care<unk>  national cancer treatment guidelines recommend early palliative care for people with advanced<unk>  at the time of diagnosis and for anyone who has significant symptoms. Palliative care is appropriate at any stage of<unk>  and can be provided alongside curative treatment. In addition to addressing symptoms of cancer, palliative care helps manage unwanted side effects, such as pain and nausea related to treatments. Teeth Oral prophylaxis, hygiene instruction and elimination of sources of infection within the mouth before beginning cancer treatment, can reduce the risk of infectious complications. Before starting bisphosphonates therapy, the
Multiple myeloma
Monoclonal gammopathy of renal significance  Monoclonal gammopathy of renal significance  1
Monoclonal gammopathy of undetermined significance
Monoclonal gammopathy of renal significance
Smouldering myeloma
Waldenström macroglobulinemia
AL amyloidosis
Plasma cell leukemia