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Multiple myeloma (MM) is a malignant disease of abnormal proliferation of clonal plasma cells [1], with a high symptom burden, often manifested as bone disease, anemia, renal insufficiency and/or metabolic abnormalities, and the patient's quality of life (QoL) ) is poor [2]
.
As MM gradually enters the mode of chronic disease management, the prevention and treatment of complications will be more critical to the improvement of patients' survival time and quality of life
.
In recent years, with the approval of a variety of drugs, such as the application of oral regimens such as ixazomib-lenalidomide-dexamethasone (IRd), the survival and compliance problems of MM have been greatly improved.
Diagnosis and treatment has gradually transformed into a chronic disease management model
.
Therefore, in addition to mastering more flexible MM treatment strategies, clinicians need to deal with the complications of MM more than ever
.
Nearly half of MM patients have pathological fractures during the disease process.
Multiple myeloma bone disease (MBD) is one of the most common complications of MM.
More than 90% of MM patients have imaging tests during the disease process, which often show different symptoms.
degree of bone disease
.
MBD is mainly due to the interaction between myeloma cells, osteoclasts, osteoblasts and bone matrix cells, which increases the activity of osteoclasts and/or weakens the activity of osteoblasts, breaking the balance between bone resorption and bone formation.
, causing bone damage [3]
.
Its clinical manifestations are osteoporosis, hypercalcemia, osteolytic destruction and pathological fractures [3]
.
The literature shows that nearly 50% of MM patients will have pathological fractures during the disease process [3]
.
Osteolytic lesions in MBD can significantly increase the risk of bone-related events (SREs), such as pathological fractures, spinal cord compression, and need for radiotherapy or surgery due to bone disease, thereby affecting overall survival and QoL and increasing treatment costs.
3]
.
After bone damage in MM, SRE persists even when good antitumor therapy is achieved, and the patient's height may also be shortened due to vertebral compression fractures [2,3]
.
Before mastering MBD treatment, let’s take a look at how to diagnose MRD.
Imaging evaluation methods include X-ray, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET-CT), etc.
.
The whole body X-ray plain film is a routine standard examination, and other detection methods are more sensitive than X-ray plain film and can detect more osteolytic lesions [3]
.
X-ray plain film: Ordinary X-ray examination is difficult to detect early lesions.
About 20% of patients with negative ordinary X-ray examination can find evidence of MM activity through other examinations
.
The exact diagnosis is based on multiple osteolytic changes and/or severe osteoporosis with fractures [3]
.
CT: CT can detect not only early bone destruction, but also osteolytic lesions that appear in the course of the disease
.
Whole-body low-dose computed tomography (WBLD-CT) is recommended to assess the extent of MBD involvement, which is helpful in discovering potential fracture risks and lesions affecting spinal stability [3]
.
MRI: MRI is currently considered to be the gold standard for evaluating the degree of bone marrow infiltration and the first choice for excluding spinal compression fractures, but it is not directly used to detect bone destruction [3]
.
PET-CT: PET-CT is a good method to detect MM activity with bone destruction, and its value lies in the evaluation of prognosis and the degree of remission of treatment, as well as the judgment of extramedullary lesions
.
Conditions should be checked as much as possible
.
When PET-CT is used to diagnose MBD, the lesion must be ≥5 mm, and when PET scans only show enhanced metabolic activity of MM without bone destruction, it is not enough to meet the diagnostic criteria[3]
.
Chinese Society of Clinical Oncology (CSCO) 2021 MBD expert consensus recommendation [3]: ordinary X-ray examination of skull and long bones of limbs; CT examination of rib lesions, including WBLD-CT; 18F-fluorodeoxyglucose positron emission tomography Scan-CT (18F-DG PET-CT) is helpful to know whether there is extramedullary plasmacytoma and minimal residual disease (MRD) detection; MRI is suitable for cervical, thoracic, lumbar, pelvic lesions and spinal cord compression examinations (evidence level : H; Recommended level: A)
.
The consensus of the International Myeloma Working Group (IMWG) pointed out that WBLD-CT is the current standard method for diagnosing MBD and is the imaging examination of choice; PET/CT is an acceptable alternative; traditional skeletal examinations are no longer available due to their low sensitivity.
is the recommended inspection method [4]
.
How is MBD treated? The consensus gives clear recommendations for the treatment of MBD, including anti-myeloma drugs, bone-targeted drug therapy, local radiotherapy, surgery, and analgesia
.
In addition, unless the acute phase of vertebral fractures, absolute bed rest is generally not recommended, otherwise decalcification is more likely to occur
.
Patients should be encouraged to engage in appropriate activities such as walking and swimming, but vigorous or confrontational exercise should be avoided
.
Patients with spondylosis should lie on a hard bed with a cushion to prevent spinal cord compression caused by vertebral fractures [3]
.
The CSCO 2021 version of the MBD expert consensus recommends the use of bone-targeted drugs on the basis of effective anti-myeloma treatment, or combined with analgesics, and radiotherapy if necessary (evidence level: H; recommendation level: A)
.
The consensus has specific recommendations for the use of bone-targeted drugs [3]: 1.
All patients treated with MM should be given bisphosphonates or denosumab; 2.
Baseline dental examinations are strongly recommended; 3.
Use of bisphosphonates During treatment, renal dysfunction and osteonecrosis of the jaw should be monitored; 4.
Bone-targeted therapy (bisphosphonates and/or denosumab) should be continued for up to 2 years; 5.
Frequency of dosing (1 per month) time or every 3 months) depends on the patient's individual condition and treatment response; 6.
When the treatment is more than 2 years, it should be based on clinical judgment
.
The consensus of the IMWG Bone Disease Working Group recommends that the first choice of treatment for MBD is zoledronic acid and denosumab
.
Regardless of whether there is imaging evidence of MBD, zoledronic acid can be used in patients with newly diagnosed MM or relapsed or refractory MM, and can also be considered in patients with biochemical recurrence; denosumab is only used in patients with MBD imaging If there is evidence, it can be considered for patients with renal insufficiency; when the first-choice drug is unavailable or contraindicated, pamidronate can be used
.
In addition, in specific cases, such as spinal cord compression, pain control, pathological fractures, etc.
, bone cement enhancement, radiation therapy and surgery should be implemented [4]
.
Prevention must be preceded by the CSCO2021 version of the MBD expert consensus that, for the prevention of MBD, the use of bisphosphonates or denosumab is recommended
.
For all symptomatic MM patients requiring systemic therapy, regardless of radiographic evidence of osteolytic lesions or osteopenia, active prevention of SRE is required
.
Densuzumab was similar to zoledronic acid in SRE prophylaxis
.
Compared with zoledronic acid, denosumab has less nephrotoxicity and is therefore preferred in patients with renal insufficiency (evidence level: I; recommendation level: A) [3]
.
The Canadian Myeloma Cooperative Group Consensus Guidelines Consortium Consensus Recommendations on the management of MM-related manifestations and complications state [2] that preservation of bone health is an important goal for all patients with MM
.
Bone mineral density (BMD), advanced age, smoking, excessive alcohol consumption, long-term glucocorticoid therapy, ethnicity, and previous low-traumatic fractures all affect bone health and make patients more prone to fractures
.
Therefore, the consensus recommends that MM patients quit smoking, reduce alcohol intake, participate in regular weight-bearing and muscle-strengthening exercise, and consume adequate vitamin D and calcium [2]
.
To be continued.
.
.
The wonderful content of MM's other complications management will be launched in the "Blood Chat Room" column one after another, so stay tuned! Reference [1] Chinese Medical Doctor Association Hematologist Branch, Chinese Medical Association Hematology Branch, Chinese Medical Doctor Association Multiple Myeloma Professional Committee.
Guidelines for the diagnosis and treatment of multiple myeloma in China (revised in 2020) [J].
Chinese Journal of Internal Medicine.
2020;59(5):341-346.
[2]LeBlanc R, Bergstrom DJ, Côté J, et al.
Management of Myeloma Manifestations and Complications: The Cornerstone of Supportive Care: Recommendation of the Canadian Myeloma Research Group (formerly Myeloma Canada Research Network) Consensus Guideline Consortium[J].
Clin Lymphoma Myeloma Leuk.
2022;22(1):e41–e56.
[3]Chinese Society of Clinical Oncology (CSCO) Guidelines Working Committee.
Expert consensus on clinical diagnosis and treatment of multiple myeloma bone disease ( 2021)[J].
Journal of Clinical Oncology.
2022;27(1):65-72.
[4]Terpos E, Zamagni E, LentzschS, et al.
Treatment of multiplemyeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group[J].
Lancet Oncol.
2021;22(3):e119-e130.
Statement: This information is intended to help healthcare professionals better understand the latest developments in related disease areas
.
The content of the information published on this site does not mean agreeing with its description and views, but only provides more information
.
If copyright issues are involved, please contact us, and we will deal with it as soon as possible
.
For informational use by healthcare professionals only
.
Such information is not intended to replace professional medical advice in any way and should not be considered medical advice
.
Takeda shall not be held responsible if such information is used for purposes other than informational understanding
.
Research material approval number: VV-MEDMAT-65136 Material approval date: 3/2022 Editor: September Layout: Wenting poke "read the original text", we will make progress together
.
As MM gradually enters the mode of chronic disease management, the prevention and treatment of complications will be more critical to the improvement of patients' survival time and quality of life
.
In recent years, with the approval of a variety of drugs, such as the application of oral regimens such as ixazomib-lenalidomide-dexamethasone (IRd), the survival and compliance problems of MM have been greatly improved.
Diagnosis and treatment has gradually transformed into a chronic disease management model
.
Therefore, in addition to mastering more flexible MM treatment strategies, clinicians need to deal with the complications of MM more than ever
.
Nearly half of MM patients have pathological fractures during the disease process.
Multiple myeloma bone disease (MBD) is one of the most common complications of MM.
More than 90% of MM patients have imaging tests during the disease process, which often show different symptoms.
degree of bone disease
.
MBD is mainly due to the interaction between myeloma cells, osteoclasts, osteoblasts and bone matrix cells, which increases the activity of osteoclasts and/or weakens the activity of osteoblasts, breaking the balance between bone resorption and bone formation.
, causing bone damage [3]
.
Its clinical manifestations are osteoporosis, hypercalcemia, osteolytic destruction and pathological fractures [3]
.
The literature shows that nearly 50% of MM patients will have pathological fractures during the disease process [3]
.
Osteolytic lesions in MBD can significantly increase the risk of bone-related events (SREs), such as pathological fractures, spinal cord compression, and need for radiotherapy or surgery due to bone disease, thereby affecting overall survival and QoL and increasing treatment costs.
3]
.
After bone damage in MM, SRE persists even when good antitumor therapy is achieved, and the patient's height may also be shortened due to vertebral compression fractures [2,3]
.
Before mastering MBD treatment, let’s take a look at how to diagnose MRD.
Imaging evaluation methods include X-ray, computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET-CT), etc.
.
The whole body X-ray plain film is a routine standard examination, and other detection methods are more sensitive than X-ray plain film and can detect more osteolytic lesions [3]
.
X-ray plain film: Ordinary X-ray examination is difficult to detect early lesions.
About 20% of patients with negative ordinary X-ray examination can find evidence of MM activity through other examinations
.
The exact diagnosis is based on multiple osteolytic changes and/or severe osteoporosis with fractures [3]
.
CT: CT can detect not only early bone destruction, but also osteolytic lesions that appear in the course of the disease
.
Whole-body low-dose computed tomography (WBLD-CT) is recommended to assess the extent of MBD involvement, which is helpful in discovering potential fracture risks and lesions affecting spinal stability [3]
.
MRI: MRI is currently considered to be the gold standard for evaluating the degree of bone marrow infiltration and the first choice for excluding spinal compression fractures, but it is not directly used to detect bone destruction [3]
.
PET-CT: PET-CT is a good method to detect MM activity with bone destruction, and its value lies in the evaluation of prognosis and the degree of remission of treatment, as well as the judgment of extramedullary lesions
.
Conditions should be checked as much as possible
.
When PET-CT is used to diagnose MBD, the lesion must be ≥5 mm, and when PET scans only show enhanced metabolic activity of MM without bone destruction, it is not enough to meet the diagnostic criteria[3]
.
Chinese Society of Clinical Oncology (CSCO) 2021 MBD expert consensus recommendation [3]: ordinary X-ray examination of skull and long bones of limbs; CT examination of rib lesions, including WBLD-CT; 18F-fluorodeoxyglucose positron emission tomography Scan-CT (18F-DG PET-CT) is helpful to know whether there is extramedullary plasmacytoma and minimal residual disease (MRD) detection; MRI is suitable for cervical, thoracic, lumbar, pelvic lesions and spinal cord compression examinations (evidence level : H; Recommended level: A)
.
The consensus of the International Myeloma Working Group (IMWG) pointed out that WBLD-CT is the current standard method for diagnosing MBD and is the imaging examination of choice; PET/CT is an acceptable alternative; traditional skeletal examinations are no longer available due to their low sensitivity.
is the recommended inspection method [4]
.
How is MBD treated? The consensus gives clear recommendations for the treatment of MBD, including anti-myeloma drugs, bone-targeted drug therapy, local radiotherapy, surgery, and analgesia
.
In addition, unless the acute phase of vertebral fractures, absolute bed rest is generally not recommended, otherwise decalcification is more likely to occur
.
Patients should be encouraged to engage in appropriate activities such as walking and swimming, but vigorous or confrontational exercise should be avoided
.
Patients with spondylosis should lie on a hard bed with a cushion to prevent spinal cord compression caused by vertebral fractures [3]
.
The CSCO 2021 version of the MBD expert consensus recommends the use of bone-targeted drugs on the basis of effective anti-myeloma treatment, or combined with analgesics, and radiotherapy if necessary (evidence level: H; recommendation level: A)
.
The consensus has specific recommendations for the use of bone-targeted drugs [3]: 1.
All patients treated with MM should be given bisphosphonates or denosumab; 2.
Baseline dental examinations are strongly recommended; 3.
Use of bisphosphonates During treatment, renal dysfunction and osteonecrosis of the jaw should be monitored; 4.
Bone-targeted therapy (bisphosphonates and/or denosumab) should be continued for up to 2 years; 5.
Frequency of dosing (1 per month) time or every 3 months) depends on the patient's individual condition and treatment response; 6.
When the treatment is more than 2 years, it should be based on clinical judgment
.
The consensus of the IMWG Bone Disease Working Group recommends that the first choice of treatment for MBD is zoledronic acid and denosumab
.
Regardless of whether there is imaging evidence of MBD, zoledronic acid can be used in patients with newly diagnosed MM or relapsed or refractory MM, and can also be considered in patients with biochemical recurrence; denosumab is only used in patients with MBD imaging If there is evidence, it can be considered for patients with renal insufficiency; when the first-choice drug is unavailable or contraindicated, pamidronate can be used
.
In addition, in specific cases, such as spinal cord compression, pain control, pathological fractures, etc.
, bone cement enhancement, radiation therapy and surgery should be implemented [4]
.
Prevention must be preceded by the CSCO2021 version of the MBD expert consensus that, for the prevention of MBD, the use of bisphosphonates or denosumab is recommended
.
For all symptomatic MM patients requiring systemic therapy, regardless of radiographic evidence of osteolytic lesions or osteopenia, active prevention of SRE is required
.
Densuzumab was similar to zoledronic acid in SRE prophylaxis
.
Compared with zoledronic acid, denosumab has less nephrotoxicity and is therefore preferred in patients with renal insufficiency (evidence level: I; recommendation level: A) [3]
.
The Canadian Myeloma Cooperative Group Consensus Guidelines Consortium Consensus Recommendations on the management of MM-related manifestations and complications state [2] that preservation of bone health is an important goal for all patients with MM
.
Bone mineral density (BMD), advanced age, smoking, excessive alcohol consumption, long-term glucocorticoid therapy, ethnicity, and previous low-traumatic fractures all affect bone health and make patients more prone to fractures
.
Therefore, the consensus recommends that MM patients quit smoking, reduce alcohol intake, participate in regular weight-bearing and muscle-strengthening exercise, and consume adequate vitamin D and calcium [2]
.
To be continued.
.
.
The wonderful content of MM's other complications management will be launched in the "Blood Chat Room" column one after another, so stay tuned! Reference [1] Chinese Medical Doctor Association Hematologist Branch, Chinese Medical Association Hematology Branch, Chinese Medical Doctor Association Multiple Myeloma Professional Committee.
Guidelines for the diagnosis and treatment of multiple myeloma in China (revised in 2020) [J].
Chinese Journal of Internal Medicine.
2020;59(5):341-346.
[2]LeBlanc R, Bergstrom DJ, Côté J, et al.
Management of Myeloma Manifestations and Complications: The Cornerstone of Supportive Care: Recommendation of the Canadian Myeloma Research Group (formerly Myeloma Canada Research Network) Consensus Guideline Consortium[J].
Clin Lymphoma Myeloma Leuk.
2022;22(1):e41–e56.
[3]Chinese Society of Clinical Oncology (CSCO) Guidelines Working Committee.
Expert consensus on clinical diagnosis and treatment of multiple myeloma bone disease ( 2021)[J].
Journal of Clinical Oncology.
2022;27(1):65-72.
[4]Terpos E, Zamagni E, LentzschS, et al.
Treatment of multiplemyeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group[J].
Lancet Oncol.
2021;22(3):e119-e130.
Statement: This information is intended to help healthcare professionals better understand the latest developments in related disease areas
.
The content of the information published on this site does not mean agreeing with its description and views, but only provides more information
.
If copyright issues are involved, please contact us, and we will deal with it as soon as possible
.
For informational use by healthcare professionals only
.
Such information is not intended to replace professional medical advice in any way and should not be considered medical advice
.
Takeda shall not be held responsible if such information is used for purposes other than informational understanding
.
Research material approval number: VV-MEDMAT-65136 Material approval date: 3/2022 Editor: September Layout: Wenting poke "read the original text", we will make progress together
