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Multiple Myeloma

(Myelomatosis; Plasma Cell Myeloma)

By

James R. Berenson

, MD, Institute for Myeloma and Bone Cancer Research

Reviewed/Revised Jun 2023
View PATIENT EDUCATION
Topic Resources

Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause pain and/or fractures, renal insufficiency, hypercalcemia, anemia, and recurrent infections. Diagnosis typically requires demonstration of M-protein (sometimes present in urine and not serum but rarely absent entirely) and/or light-chain proteinuria, and excessive plasma cells in the bone marrow. Specific treatment most often includes some combination of conventional chemotherapy, corticosteroids, and one or more additional medications such as proteasome inhibitors (eg, bortezomib, carfilzomib, ixazomib), immunomodulating agents (eg, lenalidomide, thalidomide, pomalidomide), or monoclonal antibodies (eg, daratumumab, isatuximab, elotuzumab). Antibody- and T-cell-based approaches to targeting of B-cell maturation antigen have shown efficacy. High-dose melphalan followed by autologous peripheral blood stem cell transplantation may also be used.

In the United States, the lifetime risk of getting multiple myeloma is 1 in 132 (0.76%) (1 General reference Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more General reference ). The median age is about 70 years. Prevalence in Black people is twice that in White people. There is a slight male predominance. Etiology is unknown, although chromosomal and genetic factors, radiation, and chemicals have been suggested.

The American Cancer Society estimates that in 2023 in the United States there will be about 35,730 new cases of multiple myeloma diagnosed and about 12,590 deaths are expected to occur (1 General reference Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more General reference ).

General reference

Pathophysiology of Multiple Myeloma

The M-protein (monoclonal immunoglobulin protein) produced by the malignant plasma cells is IgG in about 55% of myeloma patients and IgA in about 20%. Of patients producing either IgG or IgA, 40% also have Bence Jones proteinuria, which is free monoclonal kappa (κ) or lambda (λ) light chains in the urine. In 15 to 20% of patients, plasma cells secrete only Bence Jones protein. IgM and IgD myeloma account for about 1% of cases each; IgD myeloma is more frequent among patients of Asian descent. IgE myeloma is exceedingly rare. Rarely, patients have no M-protein in blood and urine, although the currently used serum free light chain assay now demonstrates monoclonal light chains in many of these formerly so-called nonsecretory patients.

Diffuse osteoporosis Osteoporosis Osteoporosis is a progressive metabolic bone disease that decreases bone mineral density (bone mass per unit volume), with deterioration of bone structure. Skeletal weakness leads to fractures... read more Osteoporosis or discrete osteolytic lesions are often present, with the most common sites being the pelvis, spine, ribs, femur, humerus, and skull. Lesions are caused by bone replacement by expanding plasmacytomas or by cytokines that are secreted by malignant plasma cells that activate osteoclasts and suppress osteoblasts, leading to bone loss. The osteolytic lesions are usually multiple; occasionally, they are solitary intramedullary masses. Increased bone loss may also lead to hypercalcemia Hypercalcemia Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more . Extraosseous solitary plasmacytomas are unusual but may occur in any tissue, especially in the upper respiratory tract.

In many patients, renal failure is present at diagnosis or develops during the course of the disorder. Renal failure has many causes, and most commonly, it results from deposition of light chains in the distal tubules (myeloma-related kidney disease Myeloma-Related Kidney Disease Patients with multiple myeloma overproduce monoclonal Ig light chains (Bence Jones proteins); these light chains are filtered by glomeruli, are nephrotoxic, and, in their various forms (free... read more Myeloma-Related Kidney Disease ) or hypercalcemia.

Because of lack of normal antibodies and other immune dysfunction, some patients have increased susceptibility to bacterial infection. Viral infections, especially herpes zoster infections Herpes Zoster Herpes zoster is infection that results when varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. Symptoms usually begin with pain along the affected... read more Herpes Zoster , occur as a result of treatment modalities such as proteasome inhibitors (eg, bortezomib, ixazomib, carfilzomib) and monoclonal antibodies (eg, daratumumab, elotuzumab, isatuximab).

Variant expressions of multiple myeloma occur (see table ).

Table

Symptoms and Signs of Multiple Myeloma

Persistent bone pain (especially in the back or thorax), renal failure, and recurrent bacterial infections are the most common problems on presentation, but many patients are identified when routine laboratory tests show an elevated total protein level in the blood, proteinuria, or unexplained anemia or renal failure.

Peripheral neuropathy, carpal tunnel syndrome (especially with associated amyloid disease), abnormal bleeding, and symptoms of hypercalcemia Symptoms and Signs Hypercalcemia is a total serum calcium concentration > 10.4 mg/dL (> 2.60 mmol/L) or ionized serum calcium > 5.2 mg/dL (> 1.30 mmol/L). Principal causes include hyperparathyroidism... read more (eg, polydipsia, dehydration) are common.

Lymphadenopathy and hepatosplenomegaly are unusual.

Diagnosis of Multiple Myeloma

  • Complete blood count (CBC) with platelets, peripheral blood smear, and chemistry panel (blood urea nitrogen [BUN], creatinine, calcium, uric acid, lactate dehydrogenase [LDH])

  • Serum and urine protein (on a 24-hour urine collection) electrophoresis followed by immunofixation; quantitative immunoglobulins; serum free light chains

  • X-rays (skeletal survey) and either a positron emission tomography (PET)-CT scan or whole-body MRI

  • Bone marrow examination, including conventional cytogenetics and fluorescent in situ hybridization studies (FISH)

Multiple myeloma is suspected in patients > 40 years with persistent unexplained bone pain, particularly at night or at rest, other typical symptoms, or unexplained laboratory abnormalities (such as elevated blood protein or urinary protein, hypercalcemia, renal insufficiency, or anemia) or x-rays showing a pathologic fracture or lytic lesions.

Laboratory evaluation includes routine blood tests, LDH, serum beta-2 microglobulin, urine and serum immune and protein electrophoresis, serum free light chains. Patients should also undergo a skeletal survey and, because they are more sensitive to bone disease than x-rays, either a PET-CT scan or whole-body MRI. A bone marrow examination is also required along with conventional cytogenetics and FISH studies (for review, see [1, 2] Diagnosis references Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more Diagnosis references ).

Routine blood tests include CBC and chemistry panel. Anemia is present in 80% of patients, usually normocytic-normochromic anemia with formation of rouleaux, which are clusters of 3 to 12 red blood cells that occur in stacks. White blood cell and platelet counts are usually normal. BUN, serum creatinine, LDH, beta-2 microglobulin, and serum uric acid may be elevated. Anion gap is sometimes low. Hypercalcemia is present at diagnosis in about 10% of patients.

Immune and protein electrophoresis is carried out on a serum sample and on a urine sample concentrated from a 24-hour collection to quantify the amount of urinary M-protein. Serum electrophoresis identifies M-protein in about 80 to 90% of patients. Most of the remaining 10 to 20% are patients with only free monoclonal light chains (Bence Jones protein) that can be detected using urine protein and immune electrophoresis. Rarely, patients have IgM, IgD, or IgE disease. Monoclonal protein is not evident at diagnosis in a small proportion of patients; however, during the course of the disease, more patients have evidence of monoclonal protein.

Immunofixation electrophoresis can identify the immunoglobulin class of the M-protein (IgG, IgA, or uncommonly IgD, IgM, or IgE) and can often detect light-chain protein if serum immunoelectrophoresis is falsely negative; immunofixation electrophoresis is done even when the serum test is negative if multiple myeloma is strongly suspected.

Serum free light-chain analysis with delineation of kappa and lambda ratios or differences between the involved and uninvolved light chains helps confirm the diagnosis and can also be used to monitor efficacy of therapy and provide prognostic data.

Serum level of beta-2 microglobulin is measured if the diagnosis is confirmed or very likely, and along with serum albumin is used to stage patients as part of the international staging system (see table ). Beta-2 microglobulin is a small protein on the membrane of all cells. Its concentration varies directly with tumor mass and severity of renal dysfunction.

Table

X-rays include a skeletal survey (ie, plain x-rays of skull, long bones, spine, pelvis, and ribs). Punched-out lytic lesions or diffuse osteoporosis is present in 80% of cases. Radionuclide bone scans usually are not helpful. Whole-body MRI can provide more detail and is obtained if specific sites of pain or neurologic symptoms are present. PET-CT scans provide prognostic information and can help determine whether patients have solitary plasmacytoma or multiple myeloma.

Bone marrow aspiration and biopsy Bone marrow aspiration and biopsy Anemia is a decrease in the number of red blood cells (RBCs) as measured by the red cell count, the hematocrit, or the red cell hemoglobin content. In men, anemia is defined as any of the following... read more Bone marrow aspiration and biopsy are done and reveal sheets or clusters of plasma cells; myeloma is diagnosed when ≥ 10% of the cells are of this type. However, bone marrow involvement is patchy; therefore, some samples from patients with myeloma may show <10% plasma cells. Still, the percentage of plasma cells in bone marrow is rarely normal. Plasma cell morphology does not correlate with the class of immunoglobulin synthesized. Chromosomal studies on bone marrow (eg, using cytogenetic testing methods such as FISH and immunohistochemistry) may reveal specific karyotypic abnormalities in plasma cells that can influence treatment choices and are associated with differences in survival.

  • Clonal bone marrow plasma cells or plasmacytoma

  • M-protein in plasma and/or urine

  • Organ impairment (hypercalcemia, renal insufficiency, anemia, or bony lesions)

In patients without serum M protein, myeloma is indicated by Bence Jones proteinuria > 200 mg/24 hour or abnormal serum free light chain levels, osteolytic lesions (without evidence of metastatic cancer or granulomatous disease), and sheets or clusters of plasma cells in the bone marrow.

Diagnosis references

Prognosis for Multiple Myeloma

Multiple myeloma is progressive and incurable, but median 5-year survival has improved to 58% as a result of advances in treatment (1 Prognosis reference Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more Prognosis reference ). Unfavorable prognostic signs at diagnosis are higher stage, lower serum albumin levels, higher beta-2 microglobulin levels, elevated LDH levels, specific cytogenetic abnormalities in the tumor cells, and higher levels of malignant cells in the blood. Patients initially presenting with renal failure also do poorly unless kidney function improves with therapy, which typically happens with current treatment options.

Prognosis reference

  • 1. American Cancer Society: Multiple Myeloma: Early Detection, Diagnosis, and Staging. Survival Rates for Multiple Myeloma. Atlanta, Ga., American Cancer Society; 2023.

Treatment of Multiple Myeloma

  • Conventional chemotherapy for symptomatic patients

  • Thalidomide, lenalidomide, or pomalidomide, and/or bortezomib, carfilzomib, or ixazomib, plus corticosteroids and/or conventional chemotherapy

  • Monoclonal antibodies, including elotuzumab, isatuximab, and daratumumab

  • Particularly for relapsed or refractory myeloma, selective inhibitor of nuclear export (SINE) selinexor, and the histone deacetylase inhibitor panobinostat

  • Particularly for relapsed or refractory myeloma, immune-based treatments that target B-cell maturation antigen (BCMA), which is highly expressed on myeloma cells

  • The BCL-2 (BCL2 apoptosis regulator) inhibitor venetoclax for patients whose malignant cells show the t(11;14) genetic marker

  • Maintenance therapy with corticosteroids, thalidomide, and/or lenalidomide, and proteasome inhibitors, especially oral ixazomib

  • Possibly autologous stem cell transplantation

  • Possibly radiation therapy to specific symptomatic areas that do not respond to systemic therapy

  • Treatment of complications (anemia, hypercalcemia, renal insufficiency, infections, and skeletal lesions (especially those associated with high risk of fracture)

Treatment of myeloma has improved in the past 2 decades, and long-term survival is a reasonable therapeutic target. Therapy involves direct treatment of malignant cells in symptomatic patients or those with myeloma-related organ dysfunction (anemia, renal dysfunction, hypercalcemia, or bone disease).

Risk factors for requiring rapid treatment of myeloma among patients initially presenting with organ dysfunction include

  • > 60% plasma cells in bone marrow

  • > 1 lesion on MRI

  • Serum free light chain levels > 100 mg/L

Patients with these risk factors are considered to have active myeloma and require immediate treatment even though nearly all randomized clinical trials of early treatment of these patients have not shown an improvement in overall survival. Patients without these risk factors or end-organ dysfunction probably do not benefit from immediate treatment, which is usually withheld until symptoms or complications develop.

Treatment of malignant cells

Conventional chemotherapy in the past was initial treatment of multiple myeloma, consisting of oral melphalan and prednisone given in cycles of 4 to 6 weeks for 8 to 12 cycles with monthly evaluation of response. However, superior outcomes have been achieved with the addition of either a proteasome inhibitor, such as bortezomib, carfilzomib, or ixazomib, or the immunomodulatory agents lenalidomide or thalidomide. Other chemotherapeutic agents, including cyclophosphamide, bendamustine, doxorubicin, and its analog, liposomal pegylated doxorubicin (doxorubicin liposomal), also are more effective when combined with an immunomodulatory drug (thalidomide, lenalidomide, or bortezomib). There is better survival when initial treatment includes both bortezomib and lenalidomide with corticosteroids. The addition of the monoclonal antibody daratumumab to bortezomib and dexamethasone as part of initial treatment appears to improve outcomes (1 Treatment references Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more Treatment references ).

Response to treatment (see table ) is indicated by

  • Decreases in serum and urine M-protein

  • Decreases in levels of the involved serum free light chain

  • Increases in numbers of red blood cells

  • Improvement in renal function among patients presenting with renal failure

  • Normalization of calcium levels among those presenting with elevated levels

  • Decrease in bone pain

  • Decrease in fatigue

Autologous peripheral blood stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more may be considered for patients who have adequate cardiac, hepatic, pulmonary, and renal function, particularly those whose disease is stable or responsive after several cycles of initial therapy. However, the newer treatment options are highly effective and may make transplantation less often necessary or unnecessary altogether. Recent clinical trials show longer progression-free survival, but no improvement in overall survival when patients undergo stem cell transplantation as part of initial therapy (2 Treatment references Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more Treatment references ).

Allogeneic stem cell transplantation after nonmyeloablative chemotherapy (eg, low-dose cyclophosphamide and fludarabine) or low-dose radiation therapy can produce myeloma-free survival of 5 to 10 years in some patients. However, allogeneic stem cell transplantation with myeloablative or nonmyeloablative chemotherapy remains experimental because of the high morbidity and mortality resulting from graft versus host disease Complications Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more .

Treatment of relapsed or refractory myeloma

For patients with relapsed or refractory myeloma, combinations of a proteasome inhibitor (bortezomib, ixazomib, or carfilzomib) with an immunomodulatory agent (thalidomide, lenalidomide, or pomalidomide) and chemotherapy or corticosteroids may be used. These drugs are usually combined with other effective drugs that the patient has not yet been treated with, although patients with prolonged remissions may respond to retreatment with the same regimen that led to the initial remission. Patients who fail to respond to a given combination of drugs may respond when another drug in the same class (eg, proteasome inhibitors, immunomodulatory agents, chemotherapeutic drugs) is substituted.

Monoclonal antibodies targeting proteins on myeloma cells may also be highly effective in relapsed or refractory myeloma. Monoclonal antibodies include daratumumab, isatuximab, and elotuzumab. These antibodies are more effective when combined with the immunomodulatory agents thalidomide, lenalidomide or pomalidomide, and dexamethasone. Daratumumab shows better results when combined with bortezomib and dexamethasone (3 Treatment references Multiple myeloma is a cancer of plasma cells that produce monoclonal immunoglobulin and invade and destroy adjacent bone tissue. Common manifestations include lytic lesions in bones that cause... read more Treatment references ), and both daratumumab and isatuximab also show improved efficacy when added to carfilzomib and dexamethasone. However, treatment with any of these monoclonal antibodies and only dexamethasone is effective in many patients without the costs and adverse effects of additional medications.

The selective inhibitor of nuclear export (SINE) selinexor and the histone deacetylase inhibitor (HDACi) panobinostat are especially effective when combined with other active myeloma medications.

Three effective immune treatments that target B-cell maturation antigen (BCMA) are available. These treatments include cellular therapies for myeloma, the chimeric antigen receptor (CAR)-T cell therapies idecabtagene vicleucel and ciltacabtagene autoleucel, and a bispecific antibody teclistamab that also targets CD3 on T cells. Although these treatments are effective, they can cause significant acute adverse effects (cytokine release syndrome Cytokine release syndrome Adverse effects are common in patients receiving any cancer therapy, particularly cytopenias, gastrointestinal effects, and tumor lysis and cytokine release syndromes. Patients may also have... read more , neurologic problems) and a high risk of ongoing severe infections.

Maintenance therapy

Maintenance therapy has been tried with nonchemotherapeutic drugs, including interferon alfa, which prolongs remission but does not improve survival and is associated with significant adverse effects. Following a response to corticosteroid-based regimens, corticosteroids alone are effective as a maintenance treatment.

Thalidomide may also be effective as a maintenance treatment, and lenalidomide alone or with corticosteroids is effective as maintenance treatment. However, there is some concern about secondary malignancies among patients receiving long-term lenalidomide therapy, especially after autologous stem cell transplantation Hematopoietic Stem Cell Transplantation Hematopoietic stem cell (HSC) transplantation is a rapidly evolving technique that offers a potential cure for hematologic cancers ( leukemias, lymphomas, myeloma) and other hematologic disorders... read more . Thus, the risk of developing secondary cancers must be weighed against improved survival.

The oral proteasome inhibitor ixazomib is effective as a single agent as maintenance therapy. Whether the combination of ixazomib with lenalidomide is more effective is unknown.

The role of antibodies as maintenance therapy remains to be defined.

Treatment of complications

In addition to direct treatment of malignant cells, therapy must also be directed at complications, which include

  • Anemia

  • Hypercalcemia

  • Hyperuricemia

  • Infections

  • Renal insufficiency

  • Skeletal lesions

Anemia can be treated with recombinant erythropoietin among patients whose anemia is inadequately relieved by chemotherapy. If anemia causes cardiovascular or significant systemic symptoms, packed red blood cells are transfused Red blood cells (RBCs) Whole blood can provide improved oxygen-carrying capacity, volume expansion, and replacement of clotting factors and was previously recommended for rapid massive blood loss. However, because... read more . Plasma exchange Plasma exchange Apheresis refers to the process of separating the cellular and soluble components of blood using a machine. Apheresis is often done on donors where whole blood is centrifuged to obtain individual... read more is indicated if the patient develops hyperviscosity Symptoms and Signs , which rarely occurs in patients with myeloma. Often patients are iron deficient for reasons unrelated to their myeloma and require intravenous iron. Patients with anemia should have periodic measurement of serum iron, transferrin, and ferritin levels to monitor iron stores as well as vitamin B12 levels.

Hypercalcemia is treated with vigorous saluresis, IV bisphosphonates (preferably zoledronic acid) after rehydration, and sometimes with calcitonin or prednisone. Denosumab can also be used to treat hypercalcemia especially among patients with severe renal failure. Patients should avoid calcium-containing foods, calcium supplements, and vitamin D.

Hyperuricemia may occur in some patients with high tumor burden and underlying metabolic problems. However, most patients do not require allopurinol. Allopurinol or rasburicase is indicated for patients with high levels of serum uric acid or high tumor burden and a high risk of tumor lysis syndrome Tumor Lysis and Cytokine Release Syndromes Adverse effects are common in patients receiving any cancer therapy, particularly cytopenias, gastrointestinal effects, and tumor lysis and cytokine release syndromes. Patients may also have... read more with treatment.

Infection is more likely during chemotherapy-induced neutropenia Neutropenia Neutropenia is a reduction in the blood neutrophil count. If it is severe, the risk and severity of bacterial and fungal infections increase. Focal symptoms of infection may be muted, but fever... read more . In addition, infections with the herpes zoster Herpes Zoster Herpes zoster is infection that results when varicella-zoster virus reactivates from its latent state in a posterior dorsal root ganglion. Symptoms usually begin with pain along the affected... read more Herpes Zoster virus occur frequently among patients treated with certain antimyeloma drugs, especially the proteasome inhibitors (bortezomib, carfilzomib, ixazomib) and the monoclonal antibodies (daratumumab, isatuximab, elotuzumab). The newer B-cell maturation antigen (BCMA) directed treatments are associated with a very high risk of severe infection.

Documented bacterial infections should be treated with antibiotics. Prophylactic use of antibiotics is not routinely recommended.

Prophylactic use of antiviral drugs (eg, acyclovir, valganciclovir, famciclovir) is indicated for patients receiving a proteasome inhibitor (bortezomib, carfilzomib, ixazomib) or a monoclonal antibody (daratumumab, isatuximab, elotuzumab).

Prophylactic IV immune globulin may reduce the risk of infection but is generally reserved for patients with low uninvolved immunoglobulin levels and frequent recurrent infections.

Pneumococcal vaccine Pneumococcal Vaccine Pneumococcal disease (eg, otitis media, pneumonia, sepsis, meningitis) is caused by some of the > 90 serotypes of Streptococcus pneumoniae (pneumococci). Vaccines are directed against... read more and influenza vaccine Influenza Vaccine Based on recommendations by the World Health Organization and the Centers for Disease Control and Prevention (CDC), vaccines for influenza are modified annually to include the most prevalent... read more are indicated to prevent infection but are not effective in most patients because of their disease- and treatment-related immune deficiency. Use of live vaccines is not recommended in immunocompromised patients. The nonviable recombinant zoster vaccine, unlike the earlier live-attenuated zoster vaccine, may be given to prevent herpes zoster but also is of limited effectiveness.

Renal compromise can often be ameliorated with adequate hydration. Even patients with prolonged, massive Bence Jones proteinuria ( 10 to 30 g/day) may have intact renal function if they maintain a urine output > 2000 mL/day. Dehydration combined with high-osmolar IV contrast may precipitate acute oliguric renal failure in patients with Bence Jones proteinuria. Plasma exchange may be effective in some cases. Nephrotoxic drugs should be avoided. Rapid and aggressive treatment of the underlying myeloma to reduce the levels of the nephrotoxic monoclonal immunoglobulin is important to reverse this condition.

Skeletal lesions require multiple supportive measures. Maintenance of ambulation and supplemental calcium and vitamin D help preserve bone density. Vitamin D levels should be measured at diagnosis and periodically, and dosing of vitamin D adjusted accordingly. Analgesics and palliative doses of radiation therapy (18 to 24 gray) can relieve bone pain. However, radiation therapy may cause significant toxicity and, because it suppresses bone marrow function, may impair the patient’s ability to receive cytotoxic doses of systemic chemotherapy.

Most patients, especially those with lytic lesions and generalized osteoporosis or osteopenia, should receive a monthly IV bisphosphonate (either pamidronate or zoledronic acid). Bisphosphonates reduce skeletal complications and lessen bone pain and may have an antitumor effect. For patients with potentially reversible renal failure resulting from myeloma but unrelated to hypercalcemia or with ongoing infusion reactions after bisphosphonate infusion, an option is monthly denosumab (given subcutaneously), which, unlike bisphosphonates, is not cleared by the kidneys and does not cause infusion reactions. Both bisphosphonates and denosumab may uncommonly cause osteonecrosis of the jaw. Maintaining excellent dental health and avoiding dental explants and implants are important to minimize the risk of this complication.

Treatment references

Key Points

  • Malignant plasma cells produce monoclonal immunoglobulin and invade and destroy bone.

  • Expanding plasmacytomas and cytokine secretion cause multiple, discrete, osteolytic lesions (usually in the pelvis, spine, ribs, and skull) and diffuse osteoporosis; pain, fractures, and hypercalcemia are common.

  • Anemia and renal failure are common.

  • Amyloidosis develops in about 10%, typically patients who produce excess lambda light chains.

  • Do serum and urine protein electrophoresis followed by immunofixation, quantitative immunoglobulins, and measurement of serum free light chains.

  • Do bone marrow aspiration and biopsy.

  • Symptomatic patients and those with organ dysfunction should be treated with drug therapy, which may include corticosteroids, chemotherapy drugs, proteasome inhibitors, immunomodulatory agents, monoclonal antibodies, selective inhibitors of nuclear export, histone deacetylase inhibitors, and cellular and antibody-based immune therapies targeting B-cell maturation antigen.

  • Stem cell transplantation is an option for some patients, but newer, highly effective treatment options may make it unnecessary in others.

More Information

The following English-language resources may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

  • Bal S, Giri S, Godby KN, Costa LJ: New regimens and directions in the management of newly diagnosed multiple myeloma. Am J Hematol 96:367–378, 2021. doi:10.1002/ajh.26080

  • Cowan AJ, Green DJ, Kwok M, et al: Diagnosis and management of multiple myeloma: A review. JAMA 327:464-477, 2022. doi: 10.1001/jama.2022.0003

  • Cook G, Morris CTCM: Evolution or revolution in multiple myeloma therapy and the role of the UK. Brit J Haematol 191:542–551, 2020. doi:10.1111/bjh.17148

  • Gulla A, Anderson KC: Multiple myeloma: the (r)evolution of current therapy and a glance into the future. Haematologica 105:2358–2367, 2020. doi:10.3324/haematol.2020.247015

  • Premkumar V, Bhutani D, Lentzsch S: Modern treatments and future directions for relapsed/refractory multiple myeloma patients. Clinical Lymphoma Myeloma Leuk20(11):736–743, 2020. doi:10.1016/j.clml.2020.06.023

  • Soekojo CY, Chng WJ: Treatment horizon in multiple myeloma. Eur J Haematol 109:425-440, 2022. doi: 10.1111/ejh.13840

Drugs Mentioned In This Article

Drug Name Select Trade
Velcade
KYPROLIS
NINLARO
Revlimid
Thalomid
POMALYST
DARZALEX
SARCLISA
Empliciti
Alkeran, Evomela
Albuked , Albumarc, Albuminar, Albuminex, AlbuRx , Albutein, Buminate, Flexbumin, Kedbumin, Macrotec, Plasbumin, Plasbumin-20
XPOVIO
FARYDAK
Venclexta, VENCLEXTA Starting Pack
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
Cyclophosphamide, Cytoxan, Neosar
BELRAPZO, BENDEKA, Treanda, VIVIMUSTA
Adriamycin, Adriamycin PFS, Adriamycin RDF, Rubex
Doxil, Lipodox
AK-Dex, Baycadron, Dalalone, Dalalone D.P, Dalalone L.A, Decadron, Decadron-LA, Dexabliss, Dexacort PH Turbinaire, Dexacort Respihaler, DexPak Jr TaperPak, DexPak TaperPak, Dextenza, DEXYCU, DoubleDex, Dxevo, Hemady, HiDex, Maxidex, Ocu-Dex , Ozurdex, ReadySharp Dexamethasone, Simplist Dexamethasone, Solurex, TaperDex, ZCORT, Zema-Pak, ZoDex, ZonaCort 11 Day, ZonaCort 7 Day
Fludara, Oforta
ABECMA
CARVYKTI
TECVAYLI
Reclast, Zometa, Zometa Powder
Fortical , Miacalcin
Prolia, XGEVA
Aloprim, Zyloprim
Elitek
Sitavig, Zovirax, Zovirax Cream, Zovirax Ointment, Zovirax Powder, Zovirax Suspension
Valcyte, Valcyte Powder
Famvir
Pneumovax 23, Pnu-Imune-23 , Prevnar, Prevnar 13 , Prevnar 20, VAXNEUVANCE
Aredia
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