Home > Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment (PDQ®): Treatment - Health Professional Information [NCI]
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There are several types of plasma cell neoplasms. These diseases are all associated with a monoclonal (or myeloma) protein (M protein). They include monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of the bone, extramedullary plasmacytoma, and multiple myeloma.
Incidence and Mortality
Estimated new cases and deaths from multiple myeloma in the United States in 2012:
Clinical Presentation and Evaluation
Evaluation of patients with monoclonal (or myeloma) protein (M protein)
Idiotypic myeloma cells can be found in the blood of myeloma patients in all stages of the disease.[4,5] For this reason, when treatment is indicated, systemic treatment must be considered for all patients with symptomatic plasma cell neoplasms. Patients with MGUS or asymptomatic, smoldering myeloma do not require immediate treatment but must be followed carefully for signs of disease progression.
The major challenge is to separate the stable, asymptomatic group of patients who do not require treatment from patients with progressive, symptomatic myeloma who should be treated immediately.[6,7]
Patients with a monoclonal (or myeloma) protein (M protein) in the serum and/or urine are evaluated by some of the following criteria:
In most myeloma patients, the glomeruli function normally allows only the small molecular weight proteins, such as light chains, to filter into the urine. The concentration of protein in the tubules increases as water is reabsorbed. This leads to precipitation of proteins and the formation of tubular casts, which may injure the tubular cells. With tubular lesions, the typical electrophoresis pattern shows a small albumin peak and a larger light-chain peak in the globulin region; this tubular pattern is the usual pattern found in myeloma patients.
These initial studies should be compared with subsequent values at a later time, when it is necessary to decide whether the disease is stable or progressive, responding to treatment, or getting worse.
As mentioned before, the major challenge is to separate the stable, asymptomatic group of patients who do not require treatment from patients with progressive, symptomatic myeloma who should be treated immediately.[6,7]
Monoclonal Gammopathy of Undetermined Significance (MGUS)
Patients with MGUS have an M protein in the serum without findings of multiple myeloma, macroglobulinemia, amyloidosis, or lymphoma and have fewer than 10% of plasma cells in the bone marrow.[2,16,17,18] Patients with smoldering myeloma have similar characteristics but may have more than 10% of plasma cells in the bone marrow.
These types of patients are asymptomatic and should not be treated. They must, however, be followed carefully since about 1% to 2% of MGUS patients per year will progress to develop myeloma (most commonly), amyloidosis, lymphoma, or chronic lymphocytic leukemia and may then require therapy.[18,19,20]
Virtually all cases of multiple myeloma are preceded by a gradually rising level of MGUS.[21,22,23]
Risk factors that predict disease progression include the following:
Isolated Plasmacytoma of Bone
The patient has an isolated plasmacytoma of the bone if the following are found:
When clinically indicated, MRI may reveal unsuspected bony lesions that were undetected on standard radiographs. MRI scans of the total spine may identify other bony lesions.
A patient has extramedullary plasmacytoma if the following are found:
Multiple myeloma is a systemic malignancy of plasma cells that typically involves multiple sites within the bone marrow and secretes all or part of a monoclonal antibody.
Multiple myeloma is highly treatable but rarely curable. The median survival in the prechemotherapy era was about 7 months. After the introduction of chemotherapy, prognosis improved significantly with a median survival of 24 to 30 months and a 10-year survival rate of 3%. Even further improvements in prognosis have occurred because of the introduction of newer therapies such as pulse corticosteroids, thalidomide, bortezomib, and autologous and allogeneic stem cell transplantation, with median survivals of 45 to 60 months.[32,33,34]
Multiple myeloma is potentially curable when it presents as a solitary plasmacytoma of bone or as an extramedullary plasmacytoma. (Refer to the Isolated Plasmacytoma of Bone and Extramedullary Plasmacytoma sections of this summary for more information.)
Amyloidosis Associated With Plasma Cell Neoplasms
Multiple myeloma and other plasma cell neoplasms may cause a condition called amyloidosis. Primary amyloidosis can result in severe organ dysfunction especially in the kidney, heart, or peripheral nerves. Elevated serum levels of cardiac troponins and brain natriuretic peptide are poor prognostic factors. A proposed staging system for primary systemic amyloidosis based on these serum levels requires independent and prospective confirmation.
No generally accepted staging system exists for monoclonal gammopathy of undetermined significance (MGUS), isolated plasmacytoma of bone, or extramedullary plasmacytoma. Of the plasma cell neoplasms, a staging system exists only for multiple myeloma.
Multiple myeloma is staged by estimating the myeloma tumor cell mass on the basis of the amount of monoclonal (or myeloma) protein (M protein) in the serum and/or urine, along with various clinical parameters, such as hemoglobin and serum calcium concentrations, the number of lytic bone lesions, and the presence or absence of renal failure. Impaired renal function worsens prognosis regardless of stage.
The stage of the disease at presentation is a strong determinant of survival, but it has little influence on the choice of therapy since almost all patients, except for rare patients with solitary bone tumors or extramedullary plasmacytomas, have generalized disease.
International staging system
The International Myeloma Working Group studied 11,171 patients, of whom 2,901 received high-dose therapy and 8,270 received only standard-dose therapy.
An International Staging System was derived and is shown below in Table 2.
Genetic factors and risk groups
Genetic aberrations detected by interphase fluorescence in situ hybridization (FISH) may define prognostic groups in retrospective and prospective analyses.[2,3] Short survival and shorter duration of response to therapy have been reported with t(4;14)(p16;q32), t(14; 16)(q32;q23), cytogenetic deletion of 13q-14, and deletion of 17p13 (p53 locus).[2,3,4,5,6] The question of whether the choice of therapy based on FISH analysis can influence outcome must await further study in prospective trials.
Newer clinical investigations are stratifying patients with multiple myeloma into a so-called standard-risk group, which accounts for 75% of patients and has a median survival of 3 to 6 years, and a high-risk group, which has a median survival of less than 3 years.[2,3,4,5,6,7] (See Table 3 below.) This stratification, based on cytogenetic findings, has been derived from retrospective analyses and requires prospective validation. Bone marrow samples are sent for cytogenetic and FISH analysis. Plasma cell leukemia has a particularly poor prognosis.
The major challenge in treating plasma cell neoplasms is to separate the stable, asymptomatic group of patients who do not require immediate treatment from patients with progressive, symptomatic myeloma who should be treated immediately.[1,2] Monoclonal gammopathy of undetermined significance or smoldering myeloma must be distinguished from progressive myeloma.
Asymptomatic Plasma Cell Neoplasms
Asymptomatic patients with multiple myeloma who have no lytic bone lesions and normal renal function may be initially observed safely outside the context of a clinical trial.[1,3,4] Increasing anemia is the most reliable indicator of progression.
Symptomatic Plasma Cell Neoplasms
Treatment should be given to patients with symptomatic advanced disease.
Treatment should be directed at reducing the tumor cell burden and reversing any complications of disease, such as renal failure, infection, hyperviscosity, or hypercalcemia, with appropriate medical management. (Refer to the PDQ summary on Hypercalcemia for more information.)
Response criteria have been developed for patients on clinical trials.
Current therapy for patients with symptomatic myeloma can be divided into the following categories:
Standard Treatment Options for Amyloidosis Associated With Plasma Cell Neoplasms
Standard treatment options for amyloidosis associated with plasma cell neoplasms include the following:
Two randomized trials showed prolonged overall survival (OS) with the use of oral chemotherapy with melphalan with or without colchicine versus colchicine alone.[1,2][Level of evidence: 1iiA]
As is true for all plasma cell dyscrasias, anecdotal responses for amyloidosis have been reported, as in the Southwest Oncology Group's trial (SWOG-9628 [NCT00002849]), for dexamethasone alone and in combination, including thalidomide, cyclophosphamide, melphalan, bortezomib, and lenalidomide.[3,4,5,6,7,8]
Stem cell rescue
A randomized, prospective study of 100 patients with immunoglobulin amyloidosis light chain compared melphalan plus high-dose dexamethasone with high-dose melphalan plus autologous stem cell rescue.
After a median follow-up of 3 years, median OS favored the nontransplant arm (56.9 months vs. 22.2 months; P = .04).[Level of evidence: 1iiA] The 24% transplant-related mortality in this series and others reflects the difficulties involved with high-dose chemotherapy in older patients with organ dysfunction.[9,10,11,12] A randomized trial confirming the benefit of autologous transplantation is not anticipated.
An anecdotal series describes full-intensity and reduced-intensity allogeneic stem cell transplantation.
Current Clinical Trials
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with primary systemic amyloidosis. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
General information about clinical trials is also available from the NCI Web site.
Standard Treatment Options for Monoclonal Gammopathy of Undetermined Significance (MGUS)
Standard treatment options for MGUS include the following:
Multiple myeloma, other plasma cell dyscrasia, or lymphoma will develop in 12% of patients by 10 years, 25% by 20 years, and 30% by 25 years.
All patients with MGUS should be kept under observation to detect increases in M protein levels and development of a plasma cell dyscrasia. Higher levels of initial M protein levels may correlate with increased risk of progression to multiple myeloma.[1,2] In a large retrospective report, the risk of progression at 20 years was 14% for an initial monoclonal protein level of 0.5 g/dL or less, 25% for a level of 1.5 g/dL, 41% for a level of 2.0 g/dL, 49% for a level of 2.5 g/dL, and 64% for a level of 3.0 g/dL.
Treatment is delayed until the disease progresses to the stage that symptoms or signs appear.
Patients with MGUS or smoldering myeloma do not respond more frequently, achieve longer remissions, or have improved survival if chemotherapy is started early while they are still asymptomatic as opposed to waiting for progression before treatment is initiated.[3,4,5,6] Newer therapies have not been proven to prevent or delay the progression of MGUS to a plasma cell dyscrasia.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with monoclonal gammopathy of undetermined significance. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Refer to the Waldenström macroglobulinemia section in the PDQ summary on Adult Non-Hodgkin Lymphoma Treatment for more information.
Standard Treatment Options for Isolated Plasmacytoma of Bone
Standard treatment options for isolated plasmacytoma of bone include the following:
About 25% of patients have a serum and/or urine M protein; this should disappear following adequate radiation therapy to the lytic lesion.
The survival rate of patients with isolated plasmacytoma of bone treated with radiation therapy to the lesion is greater than 50% at 10 years, which is much better than the survival rate of patients with disseminated multiple myeloma.
Most patients will eventually develop disseminated disease and require chemotherapy; almost 50% of them will do so within 2 years of diagnosis.[2,3] However, patients with serum paraprotein or Bence Jones protein, who have complete disappearance of these proteins after radiation therapy, may be expected to remain free of disease for prolonged periods.[2,4] Patients who progress to multiple myeloma tend to have good responses to chemotherapy with a median survival of 63 months after progression.[2,4]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with isolated plasmacytoma of bone. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
Standard Treatment Options for Extramedullary Plasmacytoma
Standard treatment options for extramedullary plasmacytoma include the following:
Patients with isolated plasma cell tumors of soft tissues, most commonly occurring in the tonsils, nasopharynx, or paranasal sinuses, should have skeletal x-rays and bone marrow biopsy (both of which should be negative) and evaluation for M protein in serum and urine.[1,2,3,4]
About 25% of patients have serum and/or urine M protein; this should disappear following adequate radiation.
Extramedullary plasmacytoma is a highly curable disease with progression-free survival ranging from 70% to 87% at 10 to 14 years after treatment with radiation therapy (with or without previous resection).[1,2,5]
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with extramedullary plasmacytoma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The initial approach to the patient is to evaluate the following parameters:
Treatment selection is influenced by the age and general health of the patient, prior therapy, and the presence of complications of the disease.
The choice of induction therapy is unclear at the present time; however, the current basic categories include the use of steroids, thalidomide, and lenalidomide.
Several questions are raised when therapy is being chosen for a patient with symptomatic myeloma at first presentation, including the following:
Induction therapy agents
Multiple therapeutic agents are available for induction therapy, either alone or in combinations. These include the following:
Clinical trials are needed to establish the regimens with the best efficacy and least long-term toxicity. (Refer to the Combination therapy section of this summary for a list of current clinical trials.)
Guidelines for choosing induction therapy
Until results become available, outside the context of a clinical trial, clinicians may choose induction therapy based on the following guidelines:
These guidelines require validation by ongoing clinical trials; participation in clinical trials is the preferred choice, when possible.
Since the mid-1980s, dexamethasone has been administered at a dose of 40 mg orally for 4 consecutive days, which is the same schedule used with the vincristine plus doxorubicin plus dexamethasone (VAD) regimen. Response rates of 60% to 70% in previously untreated patients appeared to be as high as those in patients treated with VAD.[12,13][Level of evidence: 3iiiDiv]
A prospective trial randomly assigned 488 patients older than 65 years to receive dexamethasone alone, melphalan plus dexamethasone, dexamethasone plus interferon-alpha, and melphalan plus prednisone (MP).
There has never been a randomized trial comparing single-agent oral dexamethasone at a traditional high dose (40 mg a day for 4 days, repeated after 4 days off) with a lower dose (≤40 mg weekly). This issue of dexamethasone dose has been evaluated in two of the following prospective, randomized trials:
Almost all ongoing clinical trials in the United States and Europe have implemented the low-dose dexamethasone schedule with or without other therapeutic agents.
Ten randomized prospective studies involving more than 4,500 patients have examined the introduction of thalidomide as induction therapy for previously untreated symptomatic patients with multiple myeloma.[16,17,18,19,20,21,22,23,24]
As previously described in the section on corticosteroids, high-dose dexamethasone can complicate interpretation of clinical trials by worsening cardiopulmonary toxicity and deaths, especially in the context of thalidomide or lenalidomide, both of which are thrombogenic agents.
Factors that have been implicated to worsen the risk of DVT include the use of high-dose dexamethasone, concomitant erythropoietic growth factors, and concomitant doxorubicin, liposomal doxorubicin, or alkylating agents.[26,27]
Personal cardiovascular risk factors can also influence the rate of DVT. Various clinical trials have included different DVT prophylaxis measures, including aspirin (81 mg–100 mg a day), warfarin, or low molecular-weight heparin, but the validity of these measures has not been studied prospectively in a randomized study.[20,22,27,28,29]
Prospective electrophysiologic monitoring provides no clear benefit over clinical evaluation for the development of clinically significant neuropathy while on thalidomide.
Lenalidomide has substantially greater myelosuppression but less neuropathy than seen with thalidomide; however, both have the same tendency for DVT.[5,30,31,32] DVT prophylaxis with 81 mg of aspirin has been proposed, but randomized clinical trials have not confirmed any benefit for this recommendation. Empirically, the greater the number of risk factors for DVT, the more intense the recommendation for prophylactic anticoagulation. (Refer to the Thalidomide section of this summary for more information about risk factors.) As a result of predominant renal clearance, lenalidomide doses need to be reduced in the setting of impaired renal function (creatinine clearance, 30–50: 10 mg per day; creatinine clearance, <30: 15 mg every other day; dialysis, 15 mg on day after dialysis).
When bortezomib was incorporated with induction therapy, patients with unfavorable molecular cytogenetics did not show any difference in PFS or OS compared with patients with more favorable risk factors. The benefit from bortezomib appears to be maintained across risk groups, but not reproducibly in all studies.[39,40,41,42,43][Level of evidence: 3iiiD]
Because bortezomib is metabolized and cleared by the liver, it appears active and well tolerated in patients with renal impairment.[9,44,45] In a retrospective, nonrandomized comparison, bortezomib administered once weekly had significantly less grade 3 to 4 peripheral neuropathy (8% vs. 28%, P < .001) with no loss of efficacy compared with standard biweekly administration.
The VAD regimen has shown activity in previously treated and in untreated patients with response rates ranging from 60% to 80%.[47,48,49,50][Level of evidence: 3iiiDiv]
Evidence is not strong that any alkylating agent is superior to any other. All standard doses and schedules produce equivalent results. The two most common regimens historically have been oral MP and oral cyclophosphamide plus prednisone.[53,54,55]
Combinations, such as those used in EST-2479, of alkylating agents and prednisone, administered simultaneously or alternately, have not proven to be superior to therapy with MP.[56,57,58,59][Level of evidence: 1iiA]
A meta-analysis of studies comparing MP with drug combinations concluded that both forms of treatment were equally effective.[Level of evidence: 1iiA] Patients who relapsed after initial therapy with cyclophosphamide and prednisone had no difference in OS (median OS, 17 months) when randomly assigned to receive vincristine plus carmustine plus melphalan plus cyclophosphamide plus prednisone or VAD.[Level of evidence: 1iiA]
Several national and international trials have been implemented to define the optimal combination regimens. Participation in these trials should be the preferred approach, when feasible. The combination regimens in these trials represent the most successful from numerous phase II reports during the last several years.
Options for combination regimens:
High-dose chemotherapy: Autologous bone marrow or peripheral stem cell transplantation
The failure of conventional therapy to cure the disease has led investigators to test the effectiveness of much higher doses of drugs such as melphalan. The development of techniques for harvesting hemopoietic stem cells, from marrow aspirates or the peripheral blood of the patient, and infusing these cells to promote hemopoietic recovery made it possible for investigators to test very large doses of chemotherapy.
Based on the experience of treating thousands of patients in this way, it is possible to draw a few conclusions, including the following:
Single autologous bone marrow or peripheral stem cell transplantation
While some prospective randomized trials, such as the U.S. Intergroup trial SWOG-9321, have shown improved survival for patients who received autologous peripheral stem cell or bone marrow transplantation after induction chemotherapy versus chemotherapy alone,[73,74,75][Level of evidence: 1iiA] other trials have not shown any survival advantage.[76,77,78,79][Level of evidence: 1iiA]
Two meta-analyses of almost 3,000 patients showed no survival advantage.[80,81][Level of evidence: 1iiA]
Even the trials suggesting improved survival showed no signs of a slowing in the relapse rate or a plateau to suggest that any of these patients had been cured.[73,74,75,82] The role of ASCT has also been questioned with the advent of novel induction therapies with high complete-remission rates.[83,84]
Tandem autologous bone marrow or peripheral stem cell transplantation
Another approach to high-dose therapy has been the use of two sequential episodes of high-dose therapy with stem cell support (tandem transplants).[85,86,87,88,89]
High-dose chemotherapy: Allogeneic bone marrow or peripheral stem cell transplantation
In a registry of 162 patients who underwent allogeneic matched sibling-donor transplants, the actuarial OS rate was 28% at 7 years.[Level of evidence: 3iiiA]
Favorable prognostic features included the following:
Many patients are not young enough or healthy enough to undergo these intensive approaches. A definite graft-versus-myeloma effect has been demonstrated, including regression of myeloma relapses following the infusion of donor lymphocytes.[97,98,99,100]
Myeloablative allogeneic stem cell transplantation has significant toxic effects (15%–40% mortality), but the possibility of a potent and possibly curative graft-versus-myeloma effect in a minority of patients may offset the high transplant-related mortality.[100,101,102]
Further research is required to make allogeneic transplants less dangerous and to find methods for initiating an autoimmune response to the myeloma cells. Nonmyeloablative allogeneic stem cell transplant is under development.[103,104,105] Such strategies aim to maintain efficacy (so called graft-versus-tumor effect) while reducing transplant-related mortality.[106,107] The lower transplant-related mortality from nonmyeloablative approaches has been accompanied by a greater risk of relapse. Given the lack of evidence so far that the high-risk patients benefit from allogeneic stem cell transplantation in this era of novel new agents, it remains debatable whether allogeneic stem cell transplantation should be offered in the first-line setting outside the context of a clinical trial.
Clinical trials exploring thalidomide as maintenance therapy have contradictory results.
Myeloma patients who respond to treatment show a progressive fall in the M protein until a plateau is reached; subsequent treatment with conventional doses does not result in any further improvement. This has led investigators to question how long treatment should be continued.
Bisphosphonates are associated with infrequent long-term complications (in 3%–5% of patients), including osteonecrosis of the jaw and avascular necrosis of the hip.[123,124] (Refer to the PDQ summary on Oral Complications of Chemotherapy and Head/Neck Radiation for more information on osteonecrosis of the jaw.) These side effects must be balanced against the potential benefits of bisphosphonates when bone metastases are evident. The optimal use and duration of bisphosphonates for bony involvement in myeloma have not been studied. Bisphosphonates are usually given intravenously on a monthly basis for 2 years and then extended at the same schedule or at a reduced schedule (i.e., once every 3–4 months), if there is evidence of active myeloma bone disease.[67,126]
Lytic lesions of the spine should be radiated if any of the following are true:
Back pain caused by osteoporosis and small compression fractures of the vertebrae responds best to chemotherapy. (Refer to the PDQ summary on Pain for more information on back pain.)
Extensive radiation of the spine or long bones for diffuse osteoporosis may lead to prolonged suppression of hemopoiesis and is rarely indicated.
Bisphosphonates are useful for slowing or reversing the osteopenia that is common in myeloma patients.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with multiple myeloma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
There are two main types of refractory myeloma patients:
A subgroup of patients who do not achieve a response to induction chemotherapy have stable disease and enjoy a survival prognosis that is as good as that for responding patients.[1,2] When the stable nature of the disease becomes established, these types of patients can discontinue therapy until the myeloma begins to progress again. Others with primary refractory myeloma and progressive disease require a change in therapy. (Refer to the Treatment for Multiple Myeloma section of this summary for more information.)
The myeloma growth rate, as measured by the monoclonal (or myeloma) protein-doubling time, for patients who respond to their initial therapy increases progressively with each subsequent relapse, and remission durations become shorter and shorter. Marrow function becomes increasingly compromised as patients develop pancytopenia and enter a refractory phase; occasionally, the myeloma cells dedifferentiate and extramedullary plasmacytomas develop. The myeloma cells may still be sensitive to chemotherapy, but the regrowth rate during relapse is so rapid that progressive improvement is not observed.
Check for U.S. clinical trials from NCI's list of cancer clinical trials that are now accepting patients with refractory multiple myeloma. The list of clinical trials can be further narrowed by location, drug, intervention, and other criteria.
The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.
General Information About Plasma Cell Neoplasms
Updated statistics with estimated new cases and deaths for 2012 (cited American Cancer Society as reference 1).
Revised text in Table 1 under clinical presentation to include asymptomatic for isolated plasmacytoma of bone and extramedullary plasmacytoma.
Added Bird et al. as reference 18.
Stage Information About Plasma Cell Neoplasms
Added Kumar et al. as reference 7.
Added text to state that plasma cell leukemia has a particularly poor prognosis (cited Ramsingh et al. as reference 8).
Treatment Option Overview for Plasma Cell Neoplasms
Added text to state that increasing anemia is the most reliable indicator of progression (cited Bladé et al. as reference 4).
Treatment for Amyloidosis Associated With Plasma Cell Neoplasms
Added text about the Southwest Oncology Group trial for dexamethasone alone and in combination, and added melphalan and bortezomib as treatments combined with thalidomide, cyclophosphamide, and lenalidomide (cited Kastritis et al. as reference 7 and Moreau et al. as reference 8).
Treatment for Monoclonal Gammopathy of Undetermined Significance (MGUS)
Added text to state that new therapies have not been proven to prevent or delay the progression of MGUS to a plasma cell dyscrasia (cited Bird et al. as reference 2).
Added Bladé et al. as reference 3.
Treatment for Multiple Myeloma
Added Raab et al. as reference 2.
Added Rajkumar et al. and Mateos et al. as references 5 and 6, respectively.
Added Bladé et al. as reference 10.
Added Kumar et al. as reference 11.
Revised text to state that there were ten randomized prospective studies involving more than 4,500 patients that examined the introduction of thalidomide as induction therapy (cited Cavo et al. as reference 23 and Lokhorst et al. as reference 24).
Revised text to state that only two of the ten randomized studies reported a survival advantage using thalidomide, and the patients in these trials were older than 65 or 75 years.
Revised text to state that a lower dose of thalidomide and a lower dose of steroids were administered than in the other studies.
Added Weber et al. as reference 27.
Revised text to state that with a median follow-up of 36 months, the Eastern Cooperative Oncology Group's (ECOG) E4A03 trial showed improved overall survival (OS) for patients in the low-dose dexamethasone arm.
Added text about a retrospective analysis of 353 patients who received lenalidomide and high-dose dexamethasone (cited Zangari et al. as reference 32 and level of evidence 3iiiA).
Added text to state that the greater the number of risk factors for deep vein thrombosis, the more intense the recommendation for prophylactic anticoagulation; also, as a result of predominant renal clearance, lenalidomide doses need to be reduced in the setting of impaired renal function (cited 2010 Dimopoulos et al. as reference 33).
Added Richardson et al. as reference 37.
Revised text to state that the benefit from bortezomib appears to be maintained across risk groups but not reproducibly in all studies (cited Avet-Loiseau et al. as reference 43).
Added 2009 Dimopoulos et al. and Morabito et al. as references 44 and 45, respectively.
Added text to state that bortezomib administered once weekly had less grade 3 to 4 peripheral neuropathy with no loss of efficacy compared with standard biweekly administration (cited Bringhen et al. as reference 46).
Added text to the list of trials of combination regimens to include ECOG-E1A06: Thalidomide + melphalan + prednisone versus lenalidomide + melphalan + prednisone.
Revised text in the options for combination regimens to include bortezomib + liposomal doxorubicin +/- dexamethasone (cited Jakubowiak et al. as reference 67).
Added text to state that upon review of eight updated trials encompassing more than 3,100 patients, at 10 years' follow-up, there was a 10% to 35% event-free survival rate and a 20% to 50% OS rate (cited Barlogie et al. as reference 72).
Added text to state that the role of autologous stem cell transplantation has been questioned with the advent of novel induction therapies with high complete-remission rates (cited Giralt et al. as reference 83 and Harousseau as reference 84).
Revised text to state that myeloablative allogeneic stem cell transplantation has significant toxic effects, but the possibility of a potent and possibly curative graft-versus-myeloma effect in a minority of patients may offset the high transplant-related mortality (cited Lokhorst et al. as reference 102).
Added text to state that the lower transplant-related mortality from nonmyeloablative approaches has been accompanied by a greater risk of relapse, and it remains debatable whether allogeneic stem cell transplantation should be offered in the first-line setting outside the context of a clinical trial.
Added text to state that clinical trials exploring thalidomide as maintenance therapy have contradictory results.
Revised text to state that maintenance interferon-alpha therapy has been reported to prolong initial remission duration after conventional chemotherapy.
Added text to state that a randomized study compared maintenance interferon with maintenance thalidomide in 103 previously untreated and treated patients who had at least a minimal response to induction chemotherapy with thalidomide, pegylated liposomal doxorubicin, and dexamethasone; with a median follow-up of 30 months, the thalidomide maintenance arm was better (cited Offidani et al. as reference 115 and level of evidence 1iiA).
Added text to state that in a trial of 556 previously untreated patients induced with thalidomide, doxorubicin, dexamethasone, and followed by high-dose melphalan with stem cell support, patients were randomly assigned to alpha interferon or to thalidomide maintenance (cited Lokhorst et al. as reference 24 and level of evidence 1iiA).
Added text about a trial of 269 patients with newly diagnosed myeloma who were given maintenance thalidomide plus prednisolone versus prednisolone alone following both induction therapy and high-dose melphalan with allogeneic stem cell transplantation and showed a benefit in favor of the thalidomide arm after a median follow-up of 3 years (cited Spencer et al. as reference 118 and level of evidence 1iiA).
Added text to state that the optimal use and duration of bisphosphonates for bony involvement in myeloma have not been studied (cited Terpos et al. as reference 126).
Added text about a double-blind, randomized, controlled trial with 504 patients with newly diagnosed multiple myeloma that compared 30 mg of pamidronate to 90 mg of pamidronate and found no difference in skeletal-related events; however, less osteonecrosis was seen in the low-dose group (cited Gimsing et al. as reference 127 and level of evidence 1iDiv).
Purpose of This Summary
This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about treatment of plasma cell neoplasms (including multiple myeloma). It is intended as a resource to inform and assist clinicians who care for cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.
Reviewers and Updates
This summary is reviewed regularly and updated as necessary by the PDQ Adult Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).
Board members review recently published articles each month to determine whether an article should:
Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.
The lead reviewers for Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment are:
Any comments or questions about the summary content should be submitted to Cancer.gov through the Web site's Contact Form. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.
Levels of Evidence
Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Adult Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.
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National Cancer Institute: PDQ® Plasma Cell Neoplasms (Including Multiple Myeloma) Treatment. Bethesda, MD: National Cancer Institute. Date last modified <MM/DD/YYYY>. Available at: http://www.cancer.gov/cancertopics/pdq/treatment/myeloma/healthprofessional. Accessed <MM/DD/YYYY>.
Images in this summary are used with permission of the author(s), artist, and/or publisher for use within the PDQ summaries only. Permission to use images outside the context of PDQ information must be obtained from the owner(s) and cannot be granted by the National Cancer Institute. Information about using the illustrations in this summary, along with many other cancer-related images, is available in Visuals Online, a collection of over 2,000 scientific images.
Based on the strength of the available evidence, treatment options may be described as either "standard" or "under clinical evaluation." These classifications should not be used as a basis for insurance reimbursement determinations. More information on insurance coverage is available on Cancer.gov on the Coping with Cancer: Financial, Insurance, and Legal Information page.
More information about contacting us or receiving help with the Cancer.gov Web site can be found on our Contact Us for Help page. Questions can also be submitted to Cancer.gov through the Web site's Contact Form.
For more information, U.S. residents may call the National Cancer Institute's (NCI's) Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237) Monday through Friday from 8:00 a.m. to 8:00 p.m., Eastern Time. A trained Cancer Information Specialist is available to answer your questions.
The NCI's LiveHelp® online chat service provides Internet users with the ability to chat online with an Information Specialist. The service is available from 8:00 a.m. to 11:00 p.m. Eastern time, Monday through Friday. Information Specialists can help Internet users find information on NCI Web sites and answer questions about cancer.
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For more information from the NCI, please write to this address:
Search the NCI Web site
The NCI Web site provides online access to information on cancer, clinical trials, and other Web sites and organizations that offer support and resources for cancer patients and their families. For a quick search, use the search box in the upper right corner of each Web page. The results for a wide range of search terms will include a list of "Best Bets," editorially chosen Web pages that are most closely related to the search term entered.
There are also many other places to get materials and information about cancer treatment and services. Hospitals in your area may have information about local and regional agencies that have information on finances, getting to and from treatment, receiving care at home, and dealing with problems related to cancer treatment.
The NCI has booklets and other materials for patients, health professionals, and the public. These publications discuss types of cancer, methods of cancer treatment, coping with cancer, and clinical trials. Some publications provide information on tests for cancer, cancer causes and prevention, cancer statistics, and NCI research activities. NCI materials on these and other topics may be ordered online or printed directly from the NCI Publications Locator. These materials can also be ordered by telephone from the Cancer Information Service toll-free at 1-800-4-CANCER (1-800-422-6237).
Last Revised: 2012-05-01
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