(3 g/dl) and clonal plasma cells <10% on bone marrow biopsy and no myeloma-related organ or tissue impairment or a related b-cell lymphoproliferative disorder related conditions include solitary plasmacytoma (a single tumor of plasma cells, typically treated with irradiation), plasma cell dyscrasia (where only the antibodies produce symptoms, e.g., al amyloidosis), and peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes. staging in multiple myeloma, staging helps with prognostication but does not guide treatment decisions. the durie-salmon staging system was used historically and was replaced by the international staging system (iss), published by the international myeloma working group in 2005. the revised iss (r-iss) was published in 2015 and incorporates cytogenetics and lactate dehydrogenase (ldh).: 1730–1 : 732–3 stage i: β2 microglobulin (β2m) < 3.5 mg/l, albumin ≥ 3.5 g/dl, normal cytogenetics, no elevated ldh stage ii: not classified under stage i or stage iii stage iii: β2m ≥ 5.5 mg/l and either elevated ldh or high-risk cytogenetics prevention the risk of multiple myeloma can be reduced slightly by maintaining a normal body weight. treatment treatment is indicated in myeloma with symptoms. if there are no symptoms, but a paraprotein typical of myeloma and diagnostic bone marrow is present without end-organ damage, treatment is usually deferred or restricted to clinical trials. treatment for multiple myeloma is focused on decreasing the clonal plasma cell population and consequently decrease the symptoms of disease. initial 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 multiple myeloma. there are two types of stem cell transplants to treat multiple myeloma. 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 as of 2008. there is support for continuous therapies with multiple drug combinations of antimyeloma drugs bortezomib, lenalidomide and thalidomide as initial treatment for transplant-ineligible multiple myeloma. 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 multiple myeloma. 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 multiple myeloma (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 multiple myeloma 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 multiple myeloma 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 multiple myeloma 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 multiple myeloma who have received at least four prior therapies stem cell transplant stem cell transplant can be used to treat multiple myeloma. 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 idecabtagene vicleucel (abecma) – first cell-based gene therapy was approved by fda in 2021 for the treatment of adults with relapsed or refractory multiple myeloma who have received at least four prior therapies 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 multiple myeloma 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 multiple myeloma 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 multiple national cancer treatment guidelines recommend early palliative care for people with advanced multiple myeloma at the time of diagnosis and for anyone who has significant symptoms. palliative care is appropriate at any stage of multiple myeloma 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 person's dental health should be evaluated to assess the risk factors to prevent the development of medication-related osteonecrosis of the jaw (mronj). if there are any symptoms or radiographic appearance of mronj like jaw pain, loose tooth, mucosal swelling, early referral to an oral surgeon is recommended. dental extractions should be avoided during the active period of treatment and treat the tooth with nonsurgical root canal treatment instead. prognosis overall the 5-year survival rate is around 54% in the united states. with high-dose therapy followed by asct, the median survival has been estimated in 2003 to be about 4.5 years, compared to a median around 3.5 years with "standard" therapy. the international staging system can help to predict survival, with a median survival (in 2005) of 62 months for stage-1 disease, 45 months for stage-2 disease, and 29 months for stage-3 disease. the median age at diagnosis is 69 years. genetic testing snp array karyotyping can detect copy number alterations of prognostic significance that may be missed by a targeted fish panel. the following table outlines the prognostic effect of various genetic findings in multiple myeloma, with chromosomal translocations designated t, followed by standard nomenclature thereof: genetic abnormalitygene(s)incidence among myelomasprognostic impact deletion/isolated monosomy 13 rb1, dis345–50%effect on prognosis is unclear trisomies 40–50%median overall survival: 7–10 years 1q21 gain, as an addition to another abnormality cks1b, anp32e35–40%median overall survival: 5 years t(11;14)(q13;q32) igh and ccnd115–20%median overall survival: 7–10 years trisomies plus any one igh translocation 15%may neutralize high risk igh and del 17p translocations hypodiploidy 13–20%unfavorable prognosis, high risk of progression t(4:14)(p16;q32) igh and fgfr3/mmset10–15%median overall survival: 5 years 17p deletion, as an addition to another abnormality tp5310%median overall survival: 5 years t(14;16) igh and c-maf2–5%median overall survival: 5 years t(6;14)(p21;q32) igh and ccnd32%median overall survival: 7–10 years t(14;20)(q32;q12) mafb1%median overall survival: 5 years epidemiology deaths from lymphomas and multiple myeloma per million persons in 2012 0–13 14–18 19–22 23–28 29–34 35–42 43–57 58–88 89–121 122–184 age-standardized death from lymphomas and multiple myeloma per 100,000 inhabitants in 2004. no data less than 1.8 1.8–3.6 3.6–5.4 5.4–7.2 7.2–9 9–10.8 10.8–12.6 12.6–14.4 14.4–16.2 16.2–18 18–19.8 more than 19.8 globally,