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Recently, Terpos and others put forward the latest recommendations of the International Myeloma Working Group (IMWG)-Bone Working Group on the treatment of multiple myeloma (MM) related bone diseases, and published them in the "Policy Review" in the journal "The Lancet Oncology" on.
These latest recommendations include: bisphosphonate use/dose and management of adverse events, desulimab use/dose and management of adverse events, and the use of other methods such as bone cement enhancement, radiation therapy, and surgery.
The updated recommendations are now excerpted/summarized for everyone to familiarize themselves with.
It is recommended to extract 01 bisphosphonate indications.
All patients with active MM should be given bisphosphonates (ie zoledronic acid or pamidronic acid), regardless of whether imaging examinations are present (level A recommendation) or absent (level B) Recommended, only zoledronic acid) MM-related bone disease.
Zoledronic acid can also be used for the treatment of MM-related hypercalcemia and is superior to pamidronic acid in this respect (level B recommendation).
Drug selection, route of administration and dosing schedule.
In symptomatic MM patients, it is recommended to administer zoledronic acid 4 mg intravenously, once every 3-4 weeks, infusion for 15 minutes, or pamidronic acid 30 mg or 90 mg, every 3- Once 4 weeks, the infusion is 45min (30mg) or 2h (90mg) for the prevention of skeletal-related events (level A recommendation).
During diagnosis and treatment, in the case of kidney damage, the dose adjustment of bisphosphonates is very important.
Compared with placebo or no treatment, only zoledronic acid showed benefits in progression-free survival and overall survival (level A recommendation).
Compared with pamidronic acid, zoledronic acid is more convenient to administer, and can also significantly reduce mortality.
Therefore, zoledronic acid may be superior to pamidronic acid (grade B recommendation).Zoledronic acid may be superior to clodronic acid because of its advantages in reducing bone-related events and improving survival, especially for patients with newly diagnosed MM and MM-related bone diseases (level A recommendation).
In the prevention of skeletal-related events, pamidronate 90mg (administered intravenously once a month) is no better than 30mg pamidronate (administered intravenously once a month) (Grade B recommendation).
For outpatients, intravenous bisphosphonates are better than intravenous pamidronate or oral clodronate (level A recommendation).
For patients who cannot receive hospital outpatient treatment, home care assisted intravenous infusion can be considered as an alternative; in this case, zoledronic acid is better than pamidronic acid because of its shorter infusion time (level D recommendation ).
The course of zoledronic acid should be administered once a month for at least 12 months (level B recommendation).
If after 12 months, a very good partial remission or better remission is obtained, the treating doctor may consider reducing the dosing frequency to once every 3 months, or according to osteoporosis recommendations to once every 6 months Or once a year, or even stop zoledronic acid.
If a good partial remission is not achieved after 12 months, you must continue to take zoledronic acid every month until a good partial remission is achieved or better.
After that, the frequency of dosing can be reduced or zoledronic acid can be discontinued (level D recommendation).
Taking into account patient-related and disease-related factors (level D recommendation; expert group consensus), pamidronic acid should be given to MM patients with active disease, and the doctor can decide whether to continue treatment.
If the drug is discontinued, zoledronic acid or pamidronic acid treatment should be restarted at the time of biochemical recurrence to reduce the risk of new bone events in clinical recurrence (level B recommendation).
Adverse reaction management Patients receiving bisphosphonates should be supplemented with calcium and vitamin D, but only after the serum calcium concentration of hypercalcemia returns to normal (level A recommendation).
Creatinine clearance, serum electrolytes and urinary albumin should be monitored monthly (only in patients treated with pamidronate), and the dose should be adjusted accordingly (level A recommendation).
02 Desulumab is recommended for indications for the treatment of newly diagnosed MM (level A recommendation) and patients with relapsed or refractory MM with evidence of MM-related bone disease (level B recommendation).
Disulumab is equivalent to zoledronic acid in delaying the time from the diagnosis of MM to the first bone-related event (level A recommendation).
Disulumab can prolong the progression-free survival of newly diagnosed MM and MM-related bone diseases suitable for autologous stem cell transplantation (grade B recommendation).
In patients with MM and renal insufficiency, desulumab may be better than zoledronic acid (level B recommendation).
Disulimab can also be used in patients with myeloma-related hypercalcemia, especially those refractory to zoledronic acid (level B recommendation).
The route of administration, dosing schedule, and course of treatment should be 120 mg subcutaneously injected monthly (A-level recommendation) of desulzumab, which is more convenient than intravenous bisphosphonate administration.
Desulimab should be administered continuously until intolerable toxicity occurs (level A recommendation).
Only after 24 months of treatment, and the patient has achieved very good partial or better remission after anti-myeloma treatment, reduction, suspension or discontinuation of the drug can be considered (level D recommendation; expert group consensus).
It is recommended to administer a single-dose bisphosphonate (such as zoledronic acid) intravenously at least 6 months after the last dose of desulzumab to prevent potential rebound effects; similarly, every 6 doses of desulzumab may also be considered Dosing once a month (level D recommendation; consensus of the expert group).
Adverse reaction management recommends that all patients receiving desulumab treatment, after the serum calcium concentration of hypercalcemia normalizes, especially patients with impaired renal function, supplement calcium and vitamin D (level A recommendation).
03 Other methods: bone cement enhancement, radiotherapy and surgery are recommended to conduct a comprehensive evaluation of bone health based on medical history, clinical examination, laboratory analysis and imaging to estimate the risk of bone-related events in all patients with MM (expert group consensus).
For patients newly diagnosed with MM who are at high risk of skeletal-related events, in addition to bone-targeted drugs, early musculoskeletal intervention should be considered (expert group consensus).
For patients with painful vertebral compression fractures, balloon expansion kyphoplasty (grade A recommendation) and vertebroplasty (grade C recommendation) are recommended.
For uncontrollable pain caused by obstructive or symptomatic spinal cord compression or pathological fractures, radiotherapy should be considered (level C recommendation).
Surgery should be considered to prevent and restore pathological fractures of long bones, spinal instability, and spinal cord compression with bone fragments in the spinal cord pathway (level C recommendation).
For pathological fractures of long bones caused by underlying plasmacytoma, adjuvant radiotherapy should be considered, especially for patients with minimal or no response to systemic anti-myeloma therapy (expert group consensus).
Summary of recommendations: Bisphosphonate or desulumab should be considered the standard treatment for MM-related bone disease.
Many factors should be considered when choosing a bone-targeted drug, including cost, convenience, patient preference and toxicity characteristics.
Zoledronic acid is the bone-targeting drug of choice for newly diagnosed MM patients, regardless of whether there is MM-related bone disease.
Once the patient has achieved good partial remission or better and has been treated with zoledronic acid every month for at least 12 months, consider reducing or stopping the frequency of zoledronic acid treatment.
Desulimab can also be considered for the treatment of MM-related bone disease and should be the first choice for patients with renal impairment.
Disulumab can prolong the progression-free survival of newly diagnosed MM patients who have MM-related bone disease and are suitable for autologous stem cell transplantation.
Due to the rebound effect associated with discontinuation, discontinuation of desulumab is challenging.
If discontinuation of desulimab, the patient should receive a single dose of zoledronic acid at least 6 months after the last dose of desulimab to prevent rebound effects.
Economic models indicate that in the United States and Europe, compared with zoledronic acid, desulimab is a cost-effective treatment.
However, these studies have limitations, that is, the cost is estimated from multiple sources, and the specific results need to be further explored.
Preventive measures are essential to avoid kidney damage, hypocalcemia, and osteonecrosis of the jaw caused by bone-targeted drug therapy.
Bone cement augmentation is effective for painful vertebral compression fractures.
For uncontrollable pain, obstructive or symptomatic spinal cord compression, or pathological fractures, radiation therapy is recommended.
In order to prevent and restore pathological fractures of long bones, spinal instability, spinal cord compression and bone fragments in the spinal canal, surgical treatment should be performed.
Reference: https://ascopost.
com/news/february-2021/updated-recommendations-on-the-treatment-of-multiple-myeloma-related-bone-disease-from-the-bone-working-group-of -the-international-myeloma-working-group/Terpos E, Zamagni E, Lentzsch S, et al.
Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group.
Lancet Oncol.
2021 Feb 2: S1470-2045(20)30559-3 stamp "Read the original", we will make progress together
These latest recommendations include: bisphosphonate use/dose and management of adverse events, desulimab use/dose and management of adverse events, and the use of other methods such as bone cement enhancement, radiation therapy, and surgery.
The updated recommendations are now excerpted/summarized for everyone to familiarize themselves with.
It is recommended to extract 01 bisphosphonate indications.
All patients with active MM should be given bisphosphonates (ie zoledronic acid or pamidronic acid), regardless of whether imaging examinations are present (level A recommendation) or absent (level B) Recommended, only zoledronic acid) MM-related bone disease.
Zoledronic acid can also be used for the treatment of MM-related hypercalcemia and is superior to pamidronic acid in this respect (level B recommendation).
Drug selection, route of administration and dosing schedule.
In symptomatic MM patients, it is recommended to administer zoledronic acid 4 mg intravenously, once every 3-4 weeks, infusion for 15 minutes, or pamidronic acid 30 mg or 90 mg, every 3- Once 4 weeks, the infusion is 45min (30mg) or 2h (90mg) for the prevention of skeletal-related events (level A recommendation).
During diagnosis and treatment, in the case of kidney damage, the dose adjustment of bisphosphonates is very important.
Compared with placebo or no treatment, only zoledronic acid showed benefits in progression-free survival and overall survival (level A recommendation).
Compared with pamidronic acid, zoledronic acid is more convenient to administer, and can also significantly reduce mortality.
Therefore, zoledronic acid may be superior to pamidronic acid (grade B recommendation).Zoledronic acid may be superior to clodronic acid because of its advantages in reducing bone-related events and improving survival, especially for patients with newly diagnosed MM and MM-related bone diseases (level A recommendation).
In the prevention of skeletal-related events, pamidronate 90mg (administered intravenously once a month) is no better than 30mg pamidronate (administered intravenously once a month) (Grade B recommendation).
For outpatients, intravenous bisphosphonates are better than intravenous pamidronate or oral clodronate (level A recommendation).
For patients who cannot receive hospital outpatient treatment, home care assisted intravenous infusion can be considered as an alternative; in this case, zoledronic acid is better than pamidronic acid because of its shorter infusion time (level D recommendation ).
The course of zoledronic acid should be administered once a month for at least 12 months (level B recommendation).
If after 12 months, a very good partial remission or better remission is obtained, the treating doctor may consider reducing the dosing frequency to once every 3 months, or according to osteoporosis recommendations to once every 6 months Or once a year, or even stop zoledronic acid.
If a good partial remission is not achieved after 12 months, you must continue to take zoledronic acid every month until a good partial remission is achieved or better.
After that, the frequency of dosing can be reduced or zoledronic acid can be discontinued (level D recommendation).
Taking into account patient-related and disease-related factors (level D recommendation; expert group consensus), pamidronic acid should be given to MM patients with active disease, and the doctor can decide whether to continue treatment.
If the drug is discontinued, zoledronic acid or pamidronic acid treatment should be restarted at the time of biochemical recurrence to reduce the risk of new bone events in clinical recurrence (level B recommendation).
Adverse reaction management Patients receiving bisphosphonates should be supplemented with calcium and vitamin D, but only after the serum calcium concentration of hypercalcemia returns to normal (level A recommendation).
Creatinine clearance, serum electrolytes and urinary albumin should be monitored monthly (only in patients treated with pamidronate), and the dose should be adjusted accordingly (level A recommendation).
02 Desulumab is recommended for indications for the treatment of newly diagnosed MM (level A recommendation) and patients with relapsed or refractory MM with evidence of MM-related bone disease (level B recommendation).
Disulumab is equivalent to zoledronic acid in delaying the time from the diagnosis of MM to the first bone-related event (level A recommendation).
Disulumab can prolong the progression-free survival of newly diagnosed MM and MM-related bone diseases suitable for autologous stem cell transplantation (grade B recommendation).
In patients with MM and renal insufficiency, desulumab may be better than zoledronic acid (level B recommendation).
Disulimab can also be used in patients with myeloma-related hypercalcemia, especially those refractory to zoledronic acid (level B recommendation).
The route of administration, dosing schedule, and course of treatment should be 120 mg subcutaneously injected monthly (A-level recommendation) of desulzumab, which is more convenient than intravenous bisphosphonate administration.
Desulimab should be administered continuously until intolerable toxicity occurs (level A recommendation).
Only after 24 months of treatment, and the patient has achieved very good partial or better remission after anti-myeloma treatment, reduction, suspension or discontinuation of the drug can be considered (level D recommendation; expert group consensus).
It is recommended to administer a single-dose bisphosphonate (such as zoledronic acid) intravenously at least 6 months after the last dose of desulzumab to prevent potential rebound effects; similarly, every 6 doses of desulzumab may also be considered Dosing once a month (level D recommendation; consensus of the expert group).
Adverse reaction management recommends that all patients receiving desulumab treatment, after the serum calcium concentration of hypercalcemia normalizes, especially patients with impaired renal function, supplement calcium and vitamin D (level A recommendation).
03 Other methods: bone cement enhancement, radiotherapy and surgery are recommended to conduct a comprehensive evaluation of bone health based on medical history, clinical examination, laboratory analysis and imaging to estimate the risk of bone-related events in all patients with MM (expert group consensus).
For patients newly diagnosed with MM who are at high risk of skeletal-related events, in addition to bone-targeted drugs, early musculoskeletal intervention should be considered (expert group consensus).
For patients with painful vertebral compression fractures, balloon expansion kyphoplasty (grade A recommendation) and vertebroplasty (grade C recommendation) are recommended.
For uncontrollable pain caused by obstructive or symptomatic spinal cord compression or pathological fractures, radiotherapy should be considered (level C recommendation).
Surgery should be considered to prevent and restore pathological fractures of long bones, spinal instability, and spinal cord compression with bone fragments in the spinal cord pathway (level C recommendation).
For pathological fractures of long bones caused by underlying plasmacytoma, adjuvant radiotherapy should be considered, especially for patients with minimal or no response to systemic anti-myeloma therapy (expert group consensus).
Summary of recommendations: Bisphosphonate or desulumab should be considered the standard treatment for MM-related bone disease.
Many factors should be considered when choosing a bone-targeted drug, including cost, convenience, patient preference and toxicity characteristics.
Zoledronic acid is the bone-targeting drug of choice for newly diagnosed MM patients, regardless of whether there is MM-related bone disease.
Once the patient has achieved good partial remission or better and has been treated with zoledronic acid every month for at least 12 months, consider reducing or stopping the frequency of zoledronic acid treatment.
Desulimab can also be considered for the treatment of MM-related bone disease and should be the first choice for patients with renal impairment.
Disulumab can prolong the progression-free survival of newly diagnosed MM patients who have MM-related bone disease and are suitable for autologous stem cell transplantation.
Due to the rebound effect associated with discontinuation, discontinuation of desulumab is challenging.
If discontinuation of desulimab, the patient should receive a single dose of zoledronic acid at least 6 months after the last dose of desulimab to prevent rebound effects.
Economic models indicate that in the United States and Europe, compared with zoledronic acid, desulimab is a cost-effective treatment.
However, these studies have limitations, that is, the cost is estimated from multiple sources, and the specific results need to be further explored.
Preventive measures are essential to avoid kidney damage, hypocalcemia, and osteonecrosis of the jaw caused by bone-targeted drug therapy.
Bone cement augmentation is effective for painful vertebral compression fractures.
For uncontrollable pain, obstructive or symptomatic spinal cord compression, or pathological fractures, radiation therapy is recommended.
In order to prevent and restore pathological fractures of long bones, spinal instability, spinal cord compression and bone fragments in the spinal canal, surgical treatment should be performed.
Reference: https://ascopost.
com/news/february-2021/updated-recommendations-on-the-treatment-of-multiple-myeloma-related-bone-disease-from-the-bone-working-group-of -the-international-myeloma-working-group/Terpos E, Zamagni E, Lentzsch S, et al.
Treatment of multiple myeloma-related bone disease: recommendations from the Bone Working Group of the International Myeloma Working Group.
Lancet Oncol.
2021 Feb 2: S1470-2045(20)30559-3 stamp "Read the original", we will make progress together
