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Multiple Myeloma

Updated : April 18, 2024





Background

Multiple myeloma (MM) is a clonal plasma cell growth condition defined by aberrant monoclonal antibody production. Excess plasma cell synthesis, if left unchecked, can lead to distinct end-organ damage.

Whenever at least one of these clinical symptoms is present, this is most usually seen: anemia, renal failure, hypercalcemia, or bone pain with lytic lesions.

With any of these findings and symptoms, the differential is obviously vast, but it is critical to keep MM in mind as part of the alternative because management is distinct and improved results are possible with appropriate treatment.

Epidemiology

Multiple myeloma is a rare illness that accounts for just around 1.8 percent of the current malignant tumors identified each year in The Us.

It is most common in the geriatric population, with a median age at diagnosis of around seventy years and somewhat more men than females (1.4:1). When compared to Whites, there appears to be a two-fold growth in black and African American populations.

Anatomy

Pathophysiology

Multiple myeloma is a phase in the progression of monoclonal gammopathy. Monoclonal gammopathy of uncertain importance, a pre-malignant, painless phase of clonal plasma cell growth, is thought to be the source (MGUS). Spotting monoclonal immune complexes in the urine or blood absent signs of end-organ damage are referred to as MGUS.

This is fairly prevalent, and it has been seen in over 3% of people over the age of 50. The cell of origin appears to be a post-germinal center plasma cell. Although, as previously stated, there is a chance of development of multiple myeloma of about 1% per year, it is usually a benign illness.

The precise causes of MGUS and its advancement to multiple myeloma are uncertain. However, as previously stated, genetic changes may result in enhanced promoter gene expression or resistance to cell death, both resulting in increased plasma cell growth and number.

According to the “second hit” concept, the original plasma cell clone may have acquired additional genomic abnormalities as a result of biological instability or anomalies in the hematopoietic milieu.

Excess monoclonal immunoglobulins can cause platelet dysfunction, renal tubular injury, and hyperviscosity, leading to bleeding, renal failure, and neurologic derangements depending on the molecular driver.

Thrombocytopenia, leukopenia, and anemia are common side effects of the increasing plasma cell clone’s marrow occupation. Furthermore, myeloma cells’ interactions with the bone microenvironment result in osteoclast activation and osteoblasts’ inhibition,

leading to bone loss. This complicated process involves various intracellular and intracellular signaling cascades and several chemokines and interleukins.

Etiology

Multiple myeloma has an unknown cause. In multiple myeloma, however, numerous changes and translocations in the promoter genes, particularly on chromosome 14, are common and presumably have a role in disease progression.

Other oncogenes, including NRAS, KRAS, and BARF, may also play a role in plasma cell proliferation. Obesity, alcohol consumption, and environmental hazards such as pesticides, organic solvents, agent orange, and radiation exposure are all factors that contribute to illness occurrence.

Genetics

Prognostic Factors

Multiple myeloma has a wide range of prognoses, and numerous factors can influence outcomes. However, stage and disease biology may be the two most important factors in prognosis.

The R-ISS staging system was created after a combination of 11 international trials was used to evaluate newly diagnosed MM patients. They discovered that R-ISS I had a five-year overall survival (OS) of 82 percent and progression-free survival (PFS) of 55 percent when divided by stage.

Five-year OS was 62 percent, and PFS was 36 percent in stage II Illness. Stages III was shown to have a five-year OS of 40% and a PFS of 24%. High-risk cytogenetic abnormalities can harm the outcome. 4.14), t (14:16), and f (14:20) are all high-risk mutations that have been demonstrated to reduce OS.

The presence of t (14:16) was associated with a PFS of 2.1 years and an OS of 4.1 years in one research. When a del (17p) was combined with mutant TP53 in a tiny study, the median PFS was 18.1 months, and the median OS was 36 months.

These variables aid in determining the overall prognosis and can be used to steer discussions with patients. However, it’s worth noting that tremendous therapeutic progress has been made in recent years, even though OS updates have yet to reflect these advancements.

Clinical History

Physical Examination

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

 

melphalan

Palliative treatment:

6

mg

Tablets

Orally 

once a day

2 - 3

weeks



Dose Adjustments

Conditioning treatment: 100 mg/m²/day IV over 30 min 2 days

carmustine

150 - 200

mg

Intravenous (IV)

as a single dose for at least six weeks
Or divided into daily injections as a dose of 75-100 mg/m2 given IV for every two days



doxorubicin

PAD regimen:

9

mg/m^2

Intravenous (IV)

on days 1 to 4 for 3 cycles in combination with bortezomib and dexamethasone.
VDT-PACE regimen: 10 mg/m^2 continuous infusion on days 1 to 4 of each cycle (in combination with bortezomib, dexamethasone, thalidomide, cisplatin, cyclophosphamide, and etoposide).



elotuzumab

Lenalidomide + dexamethasone
Indicated for multiple myeloma with 1 or 3 previous treatments
one therapeutic cycle = 28 days
Therapy should be continued until the illness gets worse or the toxicity gets too much to handle
Note: As stated in Administration, premedicate before to each dosage

Cycles 1-2 = Days 1–8 and 15–22: elotuzumab 10-mg/kg IV
Days 1–21 = Lenalidomide 25 mg orally
Days 1-22= Dexamethasone 28 mg orally in 24 hrs before elotuzumab

Cycle 3 and further
Day 1–Day 15 = Lenalidomide 25 mg orally
Days 1–21: elotuzumab (10 mg/kg) IV
Days 1-15 elotuzumab with 28 mg orally dexamethasone 24 hrs before elotuzumab
Days 8, 22 without elotuzumab: 40 mg of dexamethasone

Pomalidomide + dexamethasone
Suitable for multiple myeloma + 2 regimens
One therapy cycle = every 28 days

Cycles 1-2
Days 1-8 and 15–22 = elotuzumab 10 mg/kg IV
Days 1–21= On Days 1, 8, 15, and 22, when elotuzumab with pomalidomide 4 mg orally
Dexamethasone 28 mg orally given 3–24 hours before elotuzumab

Cycle 3 and subsequent
IV elotuzumab (20 mg/kg) on Day 1; Days 1–21: 4 mg of pomalidomide PO
Day 1 with elotuzumab, dexamethasone 8 mg
Orally administer 3–24 hours before to elotuzumab
Days 8, 15, and 22 without elotuzumab: Dexamethasone 40 mg (Age= 75 years) or 20 mg (Age= 75 years above)



daratumumab

Combination with lenalidomide or pomalidomide and dexamethasone for monotherapy (4-week course):

for weeks 1-8, a dose of 16 mg per kg was IV weekly, a total of 8 doses
for weeks 9-24, a dose of 16 mg per kg given IV for every two weeks a total of 8 doses 1st dose every two-week dosing schedule assigned till week 9
from week 25 onwards till disease progression, a dose of 16 mg per kg given IV every four weeks 1st dose every 4-week dosing schedule given till week 25
Combination with bortezomib, melphalan, and prednisone 6-week cycle:
for weeks 1-8, a dose of 16 mg per kg IV weekly, a total of 6 doses
for weeks 7-54, a dose of 16 mg per kg given IV every three weeks a total of 16 doses 1st dose every 3-week dosing schedule assigned till week 7
from week 55 onwards until disease progression, a dose of 16 mg per kg given IV every four weeks 1st dose every-4-week dosing schedule assigned till Week 55
Combination with bortezomib, thalidomide, and dexamethasone 4-week cycle:
for weeks 1-8, a dose of 16 mg per kg IV weekly, a total of 8 doses
for weeks 9-16, a dose of 16 mg per kg given IV for every two weeks a total of 4 doses 1st dose every 2-week dosing schedule assigned till week 9
Stop high dose chemotherapy and ASCT:
consolidation:
for weeks 1-8, a dose of 16 mg per kg is given IV for every two weeks 1st dose every 2-week dosing schedule is given at week one
Combination with bortezomib and dexamethasone 3-week cycle:
for weeks 1-9, a dose of 16 mg per kg IV weekly, a total of 9 doses
for weeks 10-24, a dose of 16 mg per kg given IV every three weeks a total of 5 doses 1st dose every-3-week dosing schedule given till week 10
from week 25 onwards until disease progression, a dose of 16 mg per kg IV every four weeks and 1st dose every-4-week dosing schedule given till week 25
Combination of carfilzomib and dexamethasone 4-week cycle:
for week one, a dose of 8 mg per kg IV on days 1 and 2, a total of 2 doses
for weeks 2-8, a dose of 16 mg per kg IV weekly, a total of 7 doses
for weeks 9-24, a dose of 16 mg/kg IV every two weeks, a total of 8 doses, and 1st dose every-2-week dosing schedule is given till Week 9
from week 25 onwards until disease progression, a dose of 16 mg per kg
every four weeks and 1st doses every-4-week dosing schedule till Week 25



panobinostat

Single agent:

20

mg

Orally 

once a day

for every other day of the week (total duration 21-day).
Combination regimen: 20 mg once a day for 8 cycles in combination with bortezomib and dexamethasone.
Take the missed dose 12 Hr after the scheduled time.
Do not repeat the dose if vomiting occurs; continue with the next scheduled dose.



Dose Adjustments

Hepatic impairment: Mild hepatic impairment: reduce the dose to 15 mg once a day and monitor the symptoms.
Moderate hepatic impairment: reduce the dose to 10 mg once a day and monitor for adverse effects.
Severe hepatic impairment: Terminate the use.
Hematologic toxicity: For Grade 4 (platelets < 25,000/mm3 with bleeding), ANC 500 to 750/mm3, and Anemia: Terminate the treatment temporarily, monitor symptoms, and resume at a lower dose
Nonhematologic toxicity: Cardiovascular: QTcF > 480 msec: Terminate the use of Panobinostat.
Diarrhea, abdominal cramping, loose stools, and nausea/vomiting: start antidiarrheal medication such as loperamide.

dexamethasone

20 - 40

mg

Tablet

Orally 

4 times a day



ciltacabtagene autoleucel 

Injection

Treatment includes lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by ciltacabtagene autoleucel IV infusion
Lymphodepleting chemotherapy
Fludarabine: 30mg/m2 Intravenous every day for three days
Cyclophosphamide: 300mg/m2 Intravenous every day for 3 days
Ciltacabtagene autoleucel
After 2-4 days of Lymphodepleting chemotherapy, administer 0.5-1X106 CAR-positive viable T cells/kg intravenous
Do not exceed 1X108 CAR- T cells per single infusion



ixazomib 

Indicated in the patients who have received a minimum of one therapy before
Use the drug combined with dexamethasone and lenalidomide
Continue the treatment until disease progression or unacceptable toxicity
Starting doses
ixazomib: 4 mg orally on 1st, 8th, and 15th day of a 28-day cycle
lenalidomide: 25 mg orally on the initial 21 days of a 28-day cycle. Take the medication with/without food
dexamethasone: 40 mg orally in the morning on days 1st, 8th ,15th and 22nd day of 28-days cycle



dexamethasone 

Indicated combined with various anti-myeloma products for multiple myeloma products
20 to 40 mg orally each day
Refer other combination products with dexamethasone for multiple myeloma



doxorubicin liposomal 

Intravenously administer 30 mg/m² on day 4, following the administration of bortezomib at a dose of 1.3 mg/m² on days 1, 4, 8, and 11, every three weeks



belantamab mafodotin 

Following the FDA's request, the drug company initiated the withdrawal procedure for belantamab mafodotin's US marketing authorization on November 22, 2022
The request was based on the previously reported results of the DREAMM-3 phase III trial, which did not meet the FDA's requirements for accelerated approval.
Approved as a single treatment for adults with recurrent or refractory multiple myeloma (RRMM) who already had at least four medicines, such as an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory drug.



Dose Adjustments

Dose reduction recommended for adverse effects
Initial dosage reduction: 1.9 mg/kg intravenously every three weeks
Inability to tolerate initial dose reduction: Discontinue treatment.

Adverse corneal responses
Grade 1
Corneal examination result: Mild keratopathy, superficial
BCVA change: Snellen's visual acuity has decreased from the baseline of 1 line.
Maintain the same dosage regimen.
Grade 2
Moderate superficial keratopathy is found on corneal examination
Snellen visual acuity change: reduce from baseline of 2 or 3 lines, but not worse than 20/200
Withhold until BCVA changes to Grade ≤1 and both ocular examination results improve, and then continue at the exact dosage.
Grade 3
Examination of the cornea reveals severe superficial keratopathy
Change in BCVA: Snellen visual acuity decline of more than three lines from baseline, but not worse than 20/200
Withhold until both the results of the corneal examination and the BCVA shift to Grade ≤1, then begin at a lower dosage.
Grade 4
Findings of a corneal exam: Corneal epithelial abnormality
BCVA change: Visual acuity Snellen less than 20/200
If continuing therapy, withhold until corneal examination results and BCVA improve to Grade ≤1 and continue at decreased dosage.

Thrombocytopenia
Platelet count of 25,000 to less than 50,000/mcL
Consider dose reduction or withholding
Less than 25,000 platelets
Until the platelet count reaches Grade ≤3, suspend treatment, and consider restarting at a lower dosage.
Reaction related to the infusion
2nd or 3rd Grade
Interrupt the infusion and give supportive care. Reduce the rate of infusion by at least 50% and restart the infusion after the symptoms have subsided.
Grade 4
Discontinue permanently and provide urgent care
Other adverse reactions
Grade 3
Hold off until improvement reaches Grade ≤1.
Think about starting again with a lower dosage
Grade 4
Considering a permanent pause
If continuing therapy, wait until Grade ≤1 improvement before starting again at a lower dosage.

Renal Impairment
No dose change is required for mild-to-moderate (eGFR 30-89 mL/min/1.73m2) patients.
Dialysis-resistant end-stage renal illness (eGFR 29 mL/min/1.73m2): No dosing guidelines have been developed.

Hepatic impairment
No dose change is required if the condition is mild (total bilirubin ≤1.5x ULN and any AST).
(Total bilirubin >1.5x ULN and any AST) Moderate-to-severe: No dosing guidelines have been developed.

pomalidomide 

Take 4 mg orally daily on Days 1 to 21 during successive 28-day cycles until disease continues and give with combination of low-dose dexamethasone
For low-dose dexamethasone
Take orally only on Days 1, 8, 15, and 22 of each 28 days cycle
For ≤75 years: 40 mg daily
For >75 years: 20 mg daily



daratumumab/hyaluronidase 


Indicated for Multiple myeloma newly diagnosed
Combination with melphalan, bortezomib, prednisone:
1-6 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total six doses)
7-54 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 3 weeks (total 16 doses); 1st dose is given at (week-7) of every 3 weeks dosing regimen
Starting from week-55 and continuing until disease progression occurs: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks; 1st dose is given at (week-55) of every 4 weeks dosing regimen
Combination with dexamethasone, lenalidomide:
1-8 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 8 doses)
9-24 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 8 doses); 1st dose is given at (week-9) of every 2 weeks dosing regimen
Starting from week-25 and continuing until disease progression occurs:
1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks; 1st dose is given at (week-25) of every 4 weeks dosing regimen
Combination therapy with thalidomide, bortezomib, dexamethasone:
1-8 weeks Induction: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 8 doses)
9-16 weeks Induction: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 4 doses); 1st dose is given at (week-9) of every 2 weeks dosing regimen
Stop for autologous stem cell transplant and high-dose chemotherapy
1-8 weeks Consolidation: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 4 doses); Multiple myeloma relapsed/refractory
Monotherapy:
1-8 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 8 doses)
9-24 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 8 doses); 1st dose is given at (week-9) of every 2 weeks dosing regimen
Starting from week-25 and continuing until disease progression occurs:
1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks; 1st dose is given at (week-25) of every 4 weeks dosing regimen
Combination with dexamethasone, lenalidomide:
1-8 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 8 doses)
9-24 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 8 doses); 1st dose is given at (week-9) of every 2 weeks dosing regimen
Starting from week-25 and continuing until disease progression occurs:
1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks; 1st dose is given at (week-25) of every 4 weeks dosing regimen
Combination therapy with bortezomib, dexamethasone:
1-9 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 9 doses)
10-24 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 3 weeks (total 5 doses); 1st dose is given at (week-10) of every 3 weeks dosing regimen
Starting from week-25 and continuing until disease progression occurs: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks; 1st dose is given at (week-25) of every 4 weeks dosing regimen
Combination therapy with dexamethasone and pomalidomide:
1-8 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 8 doses)
9-24 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 8 doses); 1st dose is given at (week-9) of every 2 weeks dosing regimen
Starting from week-25 and continuing until disease progression occurs:
1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks; 1st dose is given at (week-25) of every 4 weeks dosing regimen
Combination therapy with dexamethasone and carfilzomib:
1-8 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 8 doses)
9-24 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 8 doses); 1st dose is given at (week-9) of every 2 weeks dosing regimen
Starting from week-25 and continuing until disease progression occurs:
1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks; 1st dose is given at (week-25) of every 4 weeks dosing regimen
Amyloidosis
1-8 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously one time a week (total 8 doses)
9-24 weeks: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 2 weeks (total 8 doses); 1st dose is given at (week-9) of every 2 weeks dosing regimen
Starting from week-25 and continuing until disease progression occurs or a maximum of two years: 1,800 mg of daratumumab /30,000 units of hyaluronidase subcutaneously every 4 weeks



talquetamab 


Indicated for Multiple Myeloma
It is Pending FDA approval for refractory or relapsed multiple myeloma



idecabtagene vicleucel 


Indicated for Multiple Myeloma
It is specifically indicated for patients with the relapsed/multiple myeloma of refractory who received a minimum of four earlier lines of therapy, together with an immunomodulatory agent, proteasome inhibitor, anti-CD38 monoclonal antibody
Verify the accessibility of idecabtagene vicleucel prior to the start of lymphodepleting chemotherapy
The therapy course consists of cyclophosphamide and fludarabine-lymphodepleting chemotherapy after that intravenous infusion of idecabtagene vicleucel
Chemotherapy as lymphodepleting:
Cyclophosphamide 300 mg/m2 intravenously every day for three days, starting with 1st dose of fludarabine
fludarabine 30 mg/m2 intravenously every day for three days
idecabtagene vicleucel Intravenous infusion:
Following the completion of lymphodepleting chemotherapy, administer for two days
Pre-treatment with diphenhydramine and acetaminophen
The dose will depend on CAR (chimeric antigen receptor)–positive, viable T cells
The Recommended dose range is 300-460 x 106 chimeric antigen receptor (CAR)-positive, viable T cells
Within 30 min, through a gravity/ peristaltic pump, administer an autologously prepared intravenous infusion for the individual patient



melphalan flufenamide 

Administer 40 mg intravenously within a period of 30 minutes on the first day of every 28 days cycle



elranatamab-bcmm 

Indicated for people with recurrent or refractory multiple myeloma who have undergone at least four prior lines of treatment, including an inhibitor of the proteasome, an immunomodulatory drug, and an anti-CD38 monoclonal antibody.
Weekly Dosing Schedule
Premedicate before to every dosage in the step-up dosing schedule (i.e., step-up dosage 1, step-up dose 2, initial treatment dose), as advised.
Administer 12mg subcutaneous for one dose on Day 1.
Step up Dosage 2:
On Day 4, administer 32mg sub-cutaneous for 1 dose.
Maintain a minimum of 2 days between the first and second step-up doses.

First treatment dose:
On Day 8, administer 76mg sub-cutaneous for 1 dose.
Maintain a minimum of three days between step-up dosage 2 and the first treatment dose.
Second treatment dosage through Week 24
One week following the first treatment dosage, and then every week until Week 24 (subsequent treatment doses): Administer 76mg subcutaneous every week.
The interval between treatment doses should be at least six days.
Week 25 and onwards (RESPONDERS ONLY):
1 week following the Week-24 dosage, and then every 2 weeks afterward: Administer 76mg sub-cutaneous every 2 weeks.
Maintain a minimum of six days between treatment doses.
Continue until the condition worsens or the toxicity becomes intolerable.



Dose Adjustments

Restarting after a dosage delay
12mg(last administered dose)
<14 days since the last dose: Restart at step-up dosage 2 (32 mg), then increase to 76 mg if tolerated.
>14 days: Start the step-up dosing regimen at step-up dosage 1 (12 mg).
32mg (last administered dose)
<14 days since the last dose: Restart at 76mg
15 to 28 days: Step-up dosage 2 (32 mg) should be given again; 76 mg may be added one week later if tolerated.
>28 days: Start the step-up dosing regimen over at step-up dosage 1 (12 mg).

motixafortide 


Indicated for Multiple Myeloma
filgrastim:
Based on body weight, 10 mcg/Kg subcutaneously every day for four days prior to 1st dose of motixafortide and also on each day prior to each apheresis
Premedication:
Prior to each dose of the motixafortide, premedicate to diminish the risk of injection site reactions and hypersensitivity
Regimen:
Administer the following medications for nearly 30 to 60 min prior to motixafortide injection
H2 blocker (i.e., famotidine),
Leukotriene inhibitor (i.e., montelukast)
Diphenhydramine (12.5 mg Intravenously or 25 mg to 50 mg orally, or another H1-antihistamine)
An analgesic medication (i.e., acetaminophen) is suggested
motixafortide:
Based on body weight, 1.25 mg/Kg subcutaneously for nearly two minutes, 10 to 14 hours prior to starting first apheresis
If required, a 2nd dose may be administer 10 to 14 hours prior to starting third apheresis



thalidomide 

Take a dose of 200 mg orally one time a day at bedtime minimum one hour after the evening food
Total duration of therapy is 28-days treatment cycles
Dosing Considerations
During the four weeks prior to starting therapy, during therapy, during dose interruptions, and for the four weeks following therapy completion, females those who are pregnant must abstain from pregnancy



aclarubicin 

The usual dose that is recommended when initiation of therapy is 175-300 mg/m2, which is given in divided doses for a duration of 3 to 7 days via IV administration with an infusion duration of 30 minutes to one hour
With a single infusion for 3 or 4 weeks, the maintenance dose is 25 -100 mg/m2 via IV



Dose Adjustments

Limited data is available for renal or hepatic impairment

linvoseltamab 

The treatment of individuals with relapsed or refractory multiple myeloma who have progressed after at least three prior therapies is awaiting FDA approval



 

thalidomide 

For <12 years: Safety and efficacy not determined
For ≥12 years old:
Take an initial dose of 100 to 300 mg orally every day at bedtime minimum one hour after evening food



 

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK534764/

Multiple Myeloma

Updated : April 18, 2024




Multiple myeloma (MM) is a clonal plasma cell growth condition defined by aberrant monoclonal antibody production. Excess plasma cell synthesis, if left unchecked, can lead to distinct end-organ damage.

Whenever at least one of these clinical symptoms is present, this is most usually seen: anemia, renal failure, hypercalcemia, or bone pain with lytic lesions.

With any of these findings and symptoms, the differential is obviously vast, but it is critical to keep MM in mind as part of the alternative because management is distinct and improved results are possible with appropriate treatment.

Multiple myeloma is a rare illness that accounts for just around 1.8 percent of the current malignant tumors identified each year in The Us.

It is most common in the geriatric population, with a median age at diagnosis of around seventy years and somewhat more men than females (1.4:1). When compared to Whites, there appears to be a two-fold growth in black and African American populations.

Multiple myeloma is a phase in the progression of monoclonal gammopathy. Monoclonal gammopathy of uncertain importance, a pre-malignant, painless phase of clonal plasma cell growth, is thought to be the source (MGUS). Spotting monoclonal immune complexes in the urine or blood absent signs of end-organ damage are referred to as MGUS.

This is fairly prevalent, and it has been seen in over 3% of people over the age of 50. The cell of origin appears to be a post-germinal center plasma cell. Although, as previously stated, there is a chance of development of multiple myeloma of about 1% per year, it is usually a benign illness.

The precise causes of MGUS and its advancement to multiple myeloma are uncertain. However, as previously stated, genetic changes may result in enhanced promoter gene expression or resistance to cell death, both resulting in increased plasma cell growth and number.

According to the “second hit” concept, the original plasma cell clone may have acquired additional genomic abnormalities as a result of biological instability or anomalies in the hematopoietic milieu.

Excess monoclonal immunoglobulins can cause platelet dysfunction, renal tubular injury, and hyperviscosity, leading to bleeding, renal failure, and neurologic derangements depending on the molecular driver.

Thrombocytopenia, leukopenia, and anemia are common side effects of the increasing plasma cell clone’s marrow occupation. Furthermore, myeloma cells’ interactions with the bone microenvironment result in osteoclast activation and osteoblasts’ inhibition,

leading to bone loss. This complicated process involves various intracellular and intracellular signaling cascades and several chemokines and interleukins.

Multiple myeloma has an unknown cause. In multiple myeloma, however, numerous changes and translocations in the promoter genes, particularly on chromosome 14, are common and presumably have a role in disease progression.

Other oncogenes, including NRAS, KRAS, and BARF, may also play a role in plasma cell proliferation. Obesity, alcohol consumption, and environmental hazards such as pesticides, organic solvents, agent orange, and radiation exposure are all factors that contribute to illness occurrence.

Multiple myeloma has a wide range of prognoses, and numerous factors can influence outcomes. However, stage and disease biology may be the two most important factors in prognosis.

The R-ISS staging system was created after a combination of 11 international trials was used to evaluate newly diagnosed MM patients. They discovered that R-ISS I had a five-year overall survival (OS) of 82 percent and progression-free survival (PFS) of 55 percent when divided by stage.

Five-year OS was 62 percent, and PFS was 36 percent in stage II Illness. Stages III was shown to have a five-year OS of 40% and a PFS of 24%. High-risk cytogenetic abnormalities can harm the outcome. 4.14), t (14:16), and f (14:20) are all high-risk mutations that have been demonstrated to reduce OS.

The presence of t (14:16) was associated with a PFS of 2.1 years and an OS of 4.1 years in one research. When a del (17p) was combined with mutant TP53 in a tiny study, the median PFS was 18.1 months, and the median OS was 36 months.

These variables aid in determining the overall prognosis and can be used to steer discussions with patients. However, it’s worth noting that tremendous therapeutic progress has been made in recent years, even though OS updates have yet to reflect these advancements.

melphalan

Palliative treatment:

6

mg

Tablets

Orally 

once a day

2 - 3

weeks



Dose Adjustments

Conditioning treatment: 100 mg/m²/day IV over 30 min 2 days

carmustine

150 - 200

mg

Intravenous (IV)

as a single dose for at least six weeks
Or divided into daily injections as a dose of 75-100 mg/m2 given IV for every two days



doxorubicin

PAD regimen:

9

mg/m^2

Intravenous (IV)

on days 1 to 4 for 3 cycles in combination with bortezomib and dexamethasone.
VDT-PACE regimen: 10 mg/m^2 continuous infusion on days 1 to 4 of each cycle (in combination with bortezomib, dexamethasone, thalidomide, cisplatin, cyclophosphamide, and etoposide).



elotuzumab

Lenalidomide + dexamethasone
Indicated for multiple myeloma with 1 or 3 previous treatments
one therapeutic cycle = 28 days
Therapy should be continued until the illness gets worse or the toxicity gets too much to handle
Note: As stated in Administration, premedicate before to each dosage

Cycles 1-2 = Days 1–8 and 15–22: elotuzumab 10-mg/kg IV
Days 1–21 = Lenalidomide 25 mg orally
Days 1-22= Dexamethasone 28 mg orally in 24 hrs before elotuzumab

Cycle 3 and further
Day 1–Day 15 = Lenalidomide 25 mg orally
Days 1–21: elotuzumab (10 mg/kg) IV
Days 1-15 elotuzumab with 28 mg orally dexamethasone 24 hrs before elotuzumab
Days 8, 22 without elotuzumab: 40 mg of dexamethasone

Pomalidomide + dexamethasone
Suitable for multiple myeloma + 2 regimens
One therapy cycle = every 28 days

Cycles 1-2
Days 1-8 and 15–22 = elotuzumab 10 mg/kg IV
Days 1–21= On Days 1, 8, 15, and 22, when elotuzumab with pomalidomide 4 mg orally
Dexamethasone 28 mg orally given 3–24 hours before elotuzumab

Cycle 3 and subsequent
IV elotuzumab (20 mg/kg) on Day 1; Days 1–21: 4 mg of pomalidomide PO
Day 1 with elotuzumab, dexamethasone 8 mg
Orally administer 3–24 hours before to elotuzumab
Days 8, 15, and 22 without elotuzumab: Dexamethasone 40 mg (Age= 75 years) or 20 mg (Age= 75 years above)



daratumumab

Combination with lenalidomide or pomalidomide and dexamethasone for monotherapy (4-week course):

for weeks 1-8, a dose of 16 mg per kg was IV weekly, a total of 8 doses
for weeks 9-24, a dose of 16 mg per kg given IV for every two weeks a total of 8 doses 1st dose every two-week dosing schedule assigned till week 9
from week 25 onwards till disease progression, a dose of 16 mg per kg given IV every four weeks 1st dose every 4-week dosing schedule given till week 25
Combination with bortezomib, melphalan, and prednisone 6-week cycle:
for weeks 1-8, a dose of 16 mg per kg IV weekly, a total of 6 doses
for weeks 7-54, a dose of 16 mg per kg given IV every three weeks a total of 16 doses 1st dose every 3-week dosing schedule assigned till week 7
from week 55 onwards until disease progression, a dose of 16 mg per kg given IV every four weeks 1st dose every-4-week dosing schedule assigned till Week 55
Combination with bortezomib, thalidomide, and dexamethasone 4-week cycle:
for weeks 1-8, a dose of 16 mg per kg IV weekly, a total of 8 doses
for weeks 9-16, a dose of 16 mg per kg given IV for every two weeks a total of 4 doses 1st dose every 2-week dosing schedule assigned till week 9
Stop high dose chemotherapy and ASCT:
consolidation:
for weeks 1-8, a dose of 16 mg per kg is given IV for every two weeks 1st dose every 2-week dosing schedule is given at week one
Combination with bortezomib and dexamethasone 3-week cycle:
for weeks 1-9, a dose of 16 mg per kg IV weekly, a total of 9 doses
for weeks 10-24, a dose of 16 mg per kg given IV every three weeks a total of 5 doses 1st dose every-3-week dosing schedule given till week 10
from week 25 onwards until disease progression, a dose of 16 mg per kg IV every four weeks and 1st dose every-4-week dosing schedule given till week 25
Combination of carfilzomib and dexamethasone 4-week cycle:
for week one, a dose of 8 mg per kg IV on days 1 and 2, a total of 2 doses
for weeks 2-8, a dose of 16 mg per kg IV weekly, a total of 7 doses
for weeks 9-24, a dose of 16 mg/kg IV every two weeks, a total of 8 doses, and 1st dose every-2-week dosing schedule is given till Week 9
from week 25 onwards until disease progression, a dose of 16 mg per kg
every four weeks and 1st doses every-4-week dosing schedule till Week 25



panobinostat

Single agent:

20

mg

Orally 

once a day

for every other day of the week (total duration 21-day).
Combination regimen: 20 mg once a day for 8 cycles in combination with bortezomib and dexamethasone.
Take the missed dose 12 Hr after the scheduled time.
Do not repeat the dose if vomiting occurs; continue with the next scheduled dose.



Dose Adjustments

Hepatic impairment: Mild hepatic impairment: reduce the dose to 15 mg once a day and monitor the symptoms.
Moderate hepatic impairment: reduce the dose to 10 mg once a day and monitor for adverse effects.
Severe hepatic impairment: Terminate the use.
Hematologic toxicity: For Grade 4 (platelets < 25,000/mm3 with bleeding), ANC 500 to 750/mm3, and Anemia: Terminate the treatment temporarily, monitor symptoms, and resume at a lower dose
Nonhematologic toxicity: Cardiovascular: QTcF > 480 msec: Terminate the use of Panobinostat.
Diarrhea, abdominal cramping, loose stools, and nausea/vomiting: start antidiarrheal medication such as loperamide.

dexamethasone

20 - 40

mg

Tablet

Orally 

4 times a day



ciltacabtagene autoleucel 

Injection

Treatment includes lymphodepleting chemotherapy with fludarabine and cyclophosphamide, followed by ciltacabtagene autoleucel IV infusion
Lymphodepleting chemotherapy
Fludarabine: 30mg/m2 Intravenous every day for three days
Cyclophosphamide: 300mg/m2 Intravenous every day for 3 days
Ciltacabtagene autoleucel
After 2-4 days of Lymphodepleting chemotherapy, administer 0.5-1X106 CAR-positive viable T cells/kg intravenous
Do not exceed 1X108 CAR- T cells per single infusion



ixazomib