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Multiple Myeloma Drugs: Class, MOA, Brands, Uses

Multiple Myeloma Drugs

spironolactone and breast cancer multiple myeloma drugs list

Multiple Myeloma is a plasma cell dyscrasia. It is a malignant proliferation of plasma cells that gradually replace the normal marrow resulting in an immunodeficient state.

The bone marrow is replaced by monoclonal plasma cells that secrete one specific type of immunoglobulin:

  • Ig G
  • Ig A
  • Ig M
  • Ig E
  • Ig D

Sometimes only the heavy chain or the light chain part of the immunoglobulin is secreted.

Patients with multiple myeloma may have hypercalcemia, renal failure, anemia, and bony pains. This is remembered by the mnemonic “CRAB“.

Drugs that are used to treat multiple myeloma target the marrow to stop the proliferation of clonal plasma cells. In addition, some drugs such as bisphosphonates are used to treat the complications of multiple myeloma.

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Multiple Myeloma Drugs List:

Treatment of multiple myeloma should be aimed to achieve remission with the first round of the treatment regimen.

Multiple Myeloma risk stratification should be done before treatment initiation. In one study, patients were classified into three risk categories [Ref]:

  • Low risk (Disease progression was noted in 61 months):

    • No Bone involvement
    • M protein of < 3 gm/dl
    • Bence Jones Proteins of < 5 gm/day
  • Intermediate risk (Disease progression was noted in 25 months)

    • No bone involvement or
    • M protein of < 3 gm/dl or
    • Bence Jones Proteins of < 5 gm/day
  • high risk (Disease progression was noted in 10 months):

    • Bone involvement
    • M protein of > 3 gm/dl
    • Bence Jones Proteins of > 5 gm/day

The preferred induction therapy in patients who are candidates for hematopoietic stem cell transplantation is:

  • Bortezomib
  • Lenalidomide, and
  • Dexamethasone

Cyclophosphamide may replace Lenalidomide in patients with kidney disease.

Other regimens are mentioned with each drug below.

Here is a list of all the drugs used to treat multiple myeloma:

Chemotherapeutic Agents
  • Melphalan
  • Doxorubicin
  • Vincristine
  • Bortezomib
  • Carfilzomib
  • Carmustine
  • Ixazomib
  • Panobinostat
Corticosteroids
  • Prednisone
  • Dexamethasone
Monoclonal Antibodies
  • Denosumab
  • Daratumumab
  • Elotuzumab
  • Isatuximab
Interferons
  • Interferon alfa-2B
Immunosuppressants
  • Thalidomide
  • Lenalidomide
  • Pomalidomide
Anti-BCMA Antibodies
  • Belantamab mafodotin
  • Teclistamab
CAR T-Cell Therapies
  • Idecabtagene vicleucel
  • Ciltacabtagene autoleucel
Selective Inhibitors of Nuclear Export
  • Selinexor
Bisphosphonates
  • Pamidronate
  • Zoledronic acid
Colony Stimulating Factors
  • Epoetin alfa
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Latest FDA-Approved Multiple Myeloma Drugs:

There have been significant advances in the treatment of multiple myeloma over the last three years. 7 very potent new medications to treat multiple myeloma have been approved by the FDA.

Here is a list of the latest approved drugs to treat multiple myeloma [Ref]:

Multiple Myeloma Drugs approved in 2022

Date of Approval Generic Name Brand Name
February 28, 2022 [ref] Ciltacabtagene autoleucel Carvykti
October 25, 2022 [ref] Teclistamab Tecvayli

Multiple Myeloma Drugs approved in 2021

Date of Approval Generic Name Brand Name
March 27, 2021 [ref] Idecabtagene vicleucel Abecma
March 31, 2021 [ref] Isatuximab Sarclisa

Multiple Myeloma Drugs approved in 2020

Date of Approval Generic Name Brand Name
December 18, 2020 [ref] Selinexor Xpovio
August 5, 2020 [ref] Belantamab mafodotin BLENREP
August 20, 2020 [ref]  Carfilzomib Kyprolis
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Chemotherapeutic Drugs to Treat Multiple Myeloma:

Here is a list of all the chemotherapeutic drugs that have been approved by the  FDA for the treatment of Multiple Myeloma.

Chemotherapeutic Drugs to treat Multiple Myeloma

Generic Name Brand Name Date of Approval
Melphalan Alkeran, Evomela May 24, 2001 [ref]
Doxorubicin Adriamycin, Doxil, Myocet July 7, 1993 [ref]
Vincristine Marqibo, Vincasar August 9, 2012 [ref]
Bortezomib Velcade May 13, 2003 [ref]
Carfilzomib Kyprolis August 20, 2020 [ref] 
Carmustine Bicnu, Gliadel August 17, 2007 [ref]
Ixazomib Ninlaro November 20, 2015 [ref]
Panobinostat Farydak February 23, 2015 [ref]

A detail of the uses, mechanism of action, and major contraindications are discussed separately for all the chemotherapeutic drugs used to treat multiple myeloma.

Melphalan is an old chemotherapeutic drug. High-dose Melphalan followed by HSCT is still used in the treatment of multiple myeloma. It is also being studied with Daratumumab in patients who have undergone HSCT.

Another treatment regimen including Melphalan is also indicated for patients who are planning to undergo ASCT or who have undergone ASCT. This regimen includes [Ref]:

  • Carfilzomib
  • Lenalidomide
  • Dexamethasone
  • Daratumumab
  • Melphalan
Drug Name Melphalan
Trade Name Alkeran, Evomela
Company Name GlaxoSmithKline
Date of Approval May 24, 2001 [ref]

Melphalan Uses:

Patients with multiple myeloma are advised to utilize melphalan as a high-dose conditioning medication before receiving a hematopoietic stem cell transplant.

Additionally, it is suggested for the palliative therapy of multiple myeloma and the palliation of ovarian epithelial cancer that cannot be surgically removed.

Mechanism of action of Melphalan:

Melphalan forms mono adducts when it binds alkyl groups to the N-7 position of guanine and the N-3 position of adenine, which causes DNA fragmentation when repair enzymes attempt to rectify the mistake.

Additionally, it can result in DNA cross-linking, which prevents DNA strands from splitting for transcription or synthesis, from the N-7 position of one guanine to the N-7 position of another. Finally, melphalan has the ability to cause a variety of mutations.

Major Contraindications of Melphalan:

ALKERAN should be stopped until the peripheral blood cell counts have improved if the leukocyte count or platelet count drops below 3,000 cells/mcL or 100,000 cells/mcL, respectively.

Doxorubicin is a cytotoxic drug. It was found effective in patients with refractory or relapsed disease when given in combination with Bortezomib and low-dose Dexamethasone [Ref].

Liposomal Doxorubicin has been FDA-approved in combination with Bortezomib who have received at least one prior therapy that did not include Bortezomib [Ref]

Drug Name Doxorubicin
Trade Name Adriamycin, Doxil, Myocet
Company Name Pfizer Inc.
Date of Approval July 7, 1993 [ref]

Uses of Doxorubicin:

Doxorubicin is used to cause regression in disseminated neoplastic diseases like acute lymphoblastic leukemia, acute myeloblastic leukemia, Wilms’ tumor, neuroblastoma, soft tissue, and bone sarcomas, breast, ovarian, transitional cell bladder, thyroid, gastric, Hodgkin’s disease, malignant lymphoma, and bronchogenic carcinomas.

Mechanism of action of Doxorubicin:

There are several different hypothesized pathways by which doxorubicin exerts its antimitotic and cytotoxic effects.

Doxorubicin intercalates with DNA to form complexes, and by stabilizing the DNA-topoisomerase II complex, it inhibits topoisomerase II activity by obstructing the religation step of the ligation-religation process, which is catalyzed by topoisomerase II.

Major Contraindications of Doxorubicin:

individuals with a history of severely impaired myocardium or recent myocardial infarction (within the last 4-6 weeks).

Vincristine is a common drug of multiple chemotherapeutic regimens for various tumors. It has been studied in combination with Liposomal Doxorubicin and Dexamethasone as the initial cytoreductive therapy in patients with symptomatic multiple myeloma.

Drug Name Vincristine
Trade Name Marqibo, Vincasar
Company Name Eli Lilly Company
Date of Approval July 9, 2013

Uses of Vincristine:

Brain tumors, small cell lung cancer, Wilms’ tumor, neuroblastoma, sarcomas, Hodgkin disease, AML, CML.

Mechanism of action of Vincristine:

Vincristine’s anticancer effects are assumed to be predominantly a result of tubulin-mediated suppression of mitosis during metaphase.

Vincristine, like other vinca alkaloids, may impair the metabolism of amino acids, cyclic AMP, and glutathione, as well as cellular respiration, calmodulin-dependent Ca2+-transport ATPase activity, nucleic acid synthesis, and lipid synthesis.

Major Contraindications

  • Hypersensitivity
  • Intrathecal (IT) administration
  • Charcot-Marie-Tooth syndrome (demyelinating form)

​​Bortezomib is a proteasome inhibitor. It is one of the most potent and usual first-line drug in the treatment of multiple myeloma. It is usually given in combination with dexamethasone and other drugs like lenalidomide.

According to the NCCN (National Comprehensive Cancer Network), the preferred first-line regimens should include:

  • Bortezomib, Lenalidomide, and Dexamethasone
  • Bortezomib, Cyclophosphamide, Dexamethasone (Preferred in patients with kidney disease)

Other recommended regimes that include Bortezomib are [Ref]:

  • Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone
  • Bortezomib, Doxorubicin, and Dexamethasone
  • Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone
  • Daratumumab, Bortezomib, Thalidomide, and Dexamethasone
  • Dexamethasone, Thalidomide, Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide, Bortezomib (VTD-PACE)
Drug Name Bortezomib
Trade Name Velcade
Company Name Takeda Oncology
Date of Approval May 13, 2003 [ref]

Uses of Bortezomib:

Adults with multiple myeloma or mantle cell lymphoma should take the medication bortezomib.

Mechanism of action of Bortezomib:

The 26S proteasome is inhibited by the drug bortezomib’s reversible binding to its chymotrypsin-like component, stopping the degradation of numerous pro-apoptotic proteins.

Major Contraindications

Patients who are hypersensitive to bortezomib, boron, or mannitol should not use VELCADE.

A doctor with experience with antineoplastic treatment should be in charge of administering VELCADE.

When using VELCADE, complete blood counts (CBC) should be checked often.

Carfilzomib (Kyprolis) is one of the latest proteasome inhibitors. It has been found superior to Bortezomib in terms of efficacy and toxicity.

In addition, it is administered once or twice weekly with dexamethasone resulting in less frequent hospital visits and better compliance.

However, because of its cardiovascular risks, it is advised to elderly patients with caution.

Carfilzomib has also been tried in triple combination regimens with Lenalidomide and Dexamethasone with significantly improved progression-free survival of 7.9 months compared with the control group.

Carfilzomib has a synergistic effect when given in combination with panobinostat and vorinostat. The median PFS (progression-free survival) has been 12 months.

Studies are being conducted to find the best regimen. Various combination regimens include [Ref]:

  • Carfilzomib, Isatuximab, and Dexamethasone
  • Carfilzomib, Daratumumab, and Dexamethasone
  • Selinexor, Carfilzomib, Dexamethasone
Drug Name Carfilzomib
Trade Name Kyprolis
Company Name Onyx Pharmaceuticals, Inc.
Date of Approval August 20, 2020 [ref] 

Uses of Carfilzomib:

Recommended for people with multiple myeloma who have had one to three lines of treatment in conjunction with dexamethasone, lenalidomide, or daratumumab plus dexamethasone.

Additionally recommended as a single agent for people with relapsed or resistant multiple myeloma after ≥1 line of therapy

Mechanism of action of Carfilzomib:

Both the core component of the 26S proteasome and the active sites of the 20S proteasome are irreversibly bound by it.

Carfilzomib has the power to block these proteasomes specifically and permanently, which can decrease proliferation and cause apoptosis in malignant plasma cells.

Major Contraindications:

None

Carmustine has been studied with other drugs as an initial therapy for patients with multiple myeloma.

In patients undergoing autologous stem cell transplantation, Carmustine in combination with a high dose of Melphalan was associated with a higher response rate and minimal pulmonary toxicity [Ref].

Drug Name Carmustine
Trade Name Bicnu, Gliadel
Company Name Bristol-Myers Squibb, Emcure Pharmaceuticals
Date of Approval August 17, 2007 [ref]

Uses of Carmustine

For the therapy of multiple myeloma, brain tumors, Non-Hodgkin’s lymphomas, and Hodgkin’s disease.

Mechanism of action of Carmustine

DNA synthesis, RNA creation, and RNA translation are all inhibited by carmustine because it makes DNA and RNA cross-links (protein synthesis).

Additionally, glutathione reductase (carbamoylated) is bound to by carmustine and modified. The cells die as a result of this

Major Contraindications

Patients having a history of allergy to carmustine or any ingredient in the medication should not get it intravenously.

It is also contraindicated for the following conditions leukopenia, neutropenia, thrombocytopenia, aseptic meningitis, bleeding, bone marrow suppression, infection, pulmonary toxicity, and pulmonary fibrosis

Ixazomib is a proteasome inhibitor. It is one of the first of the class to get approved for the treatment of patients with multiple myeloma who had received at least one prior therapy.

In addition, because of the relatively fewer side effects, it is well tolerated if administered to elderly patients who require continuous suppressive treatment and those with high-risk cytogenetics and poor prognosis [Ref].

Drug Name Ixazomib
Trade Name Ninlaro
Company Name Takeda Pharmaceuticals
Date of Approval November 20, 2015 [ref]

Uses of Ixazomib:

Patients with multiple myeloma who have undergone at least one previous therapy are advised to use Ixazomib in addition to lenalidomide and dexamethasone.

Mechanism of action of Ixazomib:

The 20S proteasome’s CT-L proteolytic (5) site is reversibly inhibited by the N-capped dipeptidyl leucine boronic acid Ixazomib.

Ixazomib also appears to inhibit the proteolytic subunits 1 and 2 at higher doses and to promote the accumulation of ubiquitinated proteins.

Major Contraindications

None

Panobinostat (Farydak) is an FDA-approved drug for the treatment of multiple myeloma. It has been approved as a third-line treatment in patients with Multiple Myeloma who have failed at least two first-line treatment regimens.

It is approved for treating Multiple Myeloma in combination with Bortezomib and Dexamethasone.

Drug Name Panobinostat
Trade Name Farydak
Company Name Novartis
Date of Approval February 23, 2015 [ref]

Uses of Panobinostat:

Patients who have had two prior treatment regimens with bortezomib and an immunomodulatory drug are advised to use panobinostat in addition to dexamethasone and bortezomib for the treatment of multiple myeloma.

Mechanism of action of Panobinostat:

Histone deacetylase, which controls the transcription of genes, cellular differentiation, cell-cycle progression, and apoptosis, is powerfully inhibited by panobinostat. Histone and nonhistone proteins cannot be deacetylated when histone deacetylase is inhibited.

Major Contraindications:

It is not approved for usage by people who are under the age of 18
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Corticosteroids for the treatment of Multiple Myeloma:

Corticosteroids are added to most chemotherapeutic regimens. The two commonly used corticosteroids to treat multiple myeloma are:

Corticosteroids to treat Multiple Myeloma

Generic Name Brand Name Date of Approval
Prednisone Deltasone, Rayos, Winpred July 26, 2012 [ref]
Dexamethasone Baycadron, Decadron, Ciprodex, Dexamethasone Intensol, Dioptrol, Hexadrol, Dextenza, Maxidex, Neofordex, Taperdex 12 Day Taper, Tobradex 30 October 1958 [ref]

Prednisone is orally available. Although less potent than Dexamethasone, it is used to treat patients with multiple myeloma after the initial induction therapy.

In one study, a high dose (50 mg) of prednisolone on alternate days resulted in a greater therapeutic response than a low dose of 10 mg given once daily in patients with multiple myeloma who achieved remission after the induction therapy [Ref].

Drug Name Prednisone
Trade Name Deltasone, Rayos, Winpred
Company Name Geneyork Pharmaceutical
Date of Approval July 26, 2012 [ref]

Uses of prednisone in Cancers:

Treating a number of malignancies, including leukemia, lymphoma, and multiple myeloma.

Mechanism of action of prednisone:

Glucocorticosteroid; evokes slight mineralocorticoid activity and moderate anti-inflammatory effects; limits or inhibits inflammation by regulating the rate of protein synthesis, inhibiting the migration of polymorphonuclear leukocytes (PMNs) and fibroblasts, reversing capillary permeability, and stabilizing lysosomes at the cellular level;

Corticosteroids are provided in physiologic amounts to replenish low levels of endogenous hormones; greater (pharmacologic) dosages reduce inflammation.

Major Contraindications

  • Documented hypersensitivity
  • Untreated serious infections
  • Varicella

Dexamethasone is one of the most commonly used drugs in the treatment of multiple myeloma. It is given to patients with multiple myeloma at all stages and even to those with less favorable cytogenetics and poor prognosis.

Dexamethasone is six times more potent than prednisone and has a very long half-life of about 36 hours.

Dexamethasone is used n various combination regimens including initial treatment. The following treatment regimens are commonly used [Ref]:

  • Bortezomib, Lenalidomide, and Dexamethasone
  • Bortezomib, Cyclophosphamide, Dexamethasone (Preferred in patients with kidney disease)
  • Daratumumab, Lenalidomide, Bortezomib, and Dexamethasone
  • Bortezomib, Doxorubicin, and Dexamethasone
  • Daratumumab, Cyclophosphamide, Bortezomib, and Dexamethasone
  • Daratumumab, Bortezomib, Thalidomide, and Dexamethasone
  • Dexamethasone, Thalidomide, Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide, Bortezomib (VTD-PACE)

Virtually all the regimens include Dexamethasone as one of the drugs.

Drug Name Dexamethasone
Trade Name Baycadron, Decadron, Ciprodex, Dexamethasone Intensol, Dioptrol, Hexadrol, Dextenza, Maxidex, Neofordex, Taperdex 12 Day Taper, Tobradex
Company Name Pfizer CentreOne
Date of Approval 30 October 1958 [ref]

Uses of Dexamethasone:

It treats specific types of arthritis, skin, blood, kidney, eye, thyroid, and intestinal problems (including colitis), severe allergies, and asthma by reducing inflammation (swelling, heat, redness, and discomfort).

There are several cancers that can be treated with dexamethasone including multiple myeloma.

Mechanism of action of Dexamethasone:

Mineralocorticoid action is weak to nonexistent whereas glucocorticoid is potent.

Reduces inflammation by preventing the migration of polymorphonuclear leukocytes (PMNs) and decreasing capillary permeability; stabilizes cell and lysosomal membranes; increases surfactant synthesis; raises serum vitamin A concentration; and inhibits prostaglandin and proinflammatory cytokines.

It also inhibits mitosis, breaks down granulocyte aggregates, reduces capillary permeability, inhibits lymphocyte proliferation through direct cytolysis,

Major Contraindications

  • Cerebral malaria
  • Documented hypersensitivity
  • Systemic fungal infection
  • Patients taking immunosuppressive dosages of corticosteroids should not get live, attenuated vaccinations.
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Monoclonal Antibodies to treat Multiple Myeloma:

Monoclonal antibodies are among the latest molecules that are genetically engineered to target cancer cells very precisely. Because of their highly precise mechanism of action, these drugs have minimal side effects.

Monoclonal Antibodies to treat Multiple Myeloma

Generic Name Brand Name Date of Approval
Denosumab Prolia, Xgeva Feb 3, 2018  [ref]
Daratumumab Darzalex, Darzalex Faspro (first approved) November 2015 [ref]
Elotuzumab Empliciti November 30, 2015 [ref]
Isatuximab Sarclisa March 31, 2021 [ref]

Denosumab (Prolia) has been approved as a supplemental drug to treat patients with multiple myeloma who have bone involvement.

It has the advantage of subcutaneous dosing once every four weeks. In addition, unlike Zoledronic acid or other bisphosphonates, it is safe in patients with renal failure.

It has shown superiority compared to other bisphosphonates in metastatic bone diseases.

Drug Name Denosumab
Trade Name Prolia, Xgeva
Company Name Amgen Inc.
Date of Approval June 2010  [ref]

Uses of Denosumab:

Xgeva is indicated for patients with multiple myeloma as well as those who have bone metastases from cancers such as the breast, prostate, and other solid malignancies.

Mechanism of action of Denosumab:

Monoclonal antibody that selectively targets RANKL; binds to RANKL and inhibits its binding to the RANK receptor, inhibiting osteoclast production; lowers bone resorption and increases bone mass in osteoporosis; decreases tumor-induced bone degradation and SREs in solid tumors with skeletal metastases.

Major Contraindications:

  • Pregnancy (Prolia only)
  • Hypocalcemia
  • Hypersensitivity

Daratumumab (Darzalex) is a drug-antibody conjugate. It targets cells that are CD 38 positive. Plasma cells of multiple myeloma patients express CD 38 in abundance and hence the role of Daratumumab is extremely beneficial in these patients.

Initially, Daratumumab monotherapy was approved as a third-line drug for the treatment of patients with multiple myeloma who had failed three first-line therapies including regimens containing Bortezomib and Lenalidomide.

Later in 2016, it was approved in combination with Lenalidomide and Dexamethasone or Bortezomib and Dexamethasone for treating multiple myeloma who had received at least one prior therapy.

Drug Name Daratumumab
Trade Name Darzalex, Darzalex Faspro
Company Name Genmab, Janssen Biotech
Date of Approval (first approved) November 2015 [ref]

Uses of Daratumumab:

Multiple myeloma can be treated with an intravenous injection of daratumumab alone or in combination with other drugs.

Adults with multiple myeloma can get it as a combination product with hyaluronidase as part of monotherapy or combination therapy, as well as in combination with other medications to treat light chain amyloidosis.

Mechanism of action of Daratumumab

This is a high-affinity monoclonal antibody that recognizes the multiple myeloma cell surface protein CD38, which is abundantly expressed,

Rapid tumor cell death is thought to be induced by binding to CD38 through a variety of immune-mediated processes, including complement-dependent cytotoxicity, antibody-dependent cellular phagocytosis, and antibody-dependent cellular cytotoxicity.

Major Contraindications:

Hypersensitivity to this medicine or formulation ingredients

Elotuzumab (Emplciti) has been approved for the treatment of Multiple Myeloma who have received at least one prior therapy.

It is given in combination with Lenalidomide and Dexamethasone.

Drug Name Elotuzumab
Trade Name Empliciti
Company Name Bristol-Myers Squibb and AbbVie
Date of Approval November 30, 2015 [ref]

Uses of Elotuzumab:

This is recommended for use in patients with multiple myeloma who have undergone one to three previous treatments, along with lenalidomide and dexamethasone.

Mechanism of action of Elotuzumab:

Elotuzumab is a humanized IgG1 monoclonal antibody that primarily affects the SLAMF7 (signaling lymphocytic activation molecule family member 7) protein.

This also attacks SLAMF7 on myeloma cells and simplifies the process for natural killer cells to communicate with them to facilitate the killing of myeloma cells through antibody-dependent cellular cytotoxicity (ADCC)

Major Contraindications:

None

Isatuximab (Sarclisa) is an anti-CD 38 antibody. It has been approved for the treatment of patients with multiple myeloma who have received one to three prior therapies.

It is given in treatment regimens that include:

  • Isatuximab, Pomalidomide, and Dexamethasone
  • Isatuximab, Carfilzomib, and Dexamethasone
Drug Name Isatuximab
Trade Name Sarclisa
Company Name Sanofi Aventis
Date of Approval March 31, 2021 [ref]

Uses of Isatuximab:

Adults with multiple myeloma who have had at least two previous therapy, such as lenalidomide and a proteasome inhibitor, are eligible to receive Isatuximab in combination with pomalidomide and dexamethasone.

Mechanism of action of Isatuximab:

IgG1-derived monoclonal antibody Isatuximab is directed against CD38 proteins.

Direct apoptosis of the affected cell as well as the activation of immune mechanisms such as antibody-dependent cell-mediated cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), all of which have potent anti-tumor activity, are caused by its activity against CD38.

Isatuximab also blocks the ectoenzymatic activity of CD38, inhibiting the immunosuppressive effects of its subsequent products through allosteric antagonism.

Major Contraindications

hypersensitivity to Isatuximab or any of its excipients on a severe level
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Interferon for the treatment of Multiple Myeloma:

Interferons are indicated for the treatment of multiple immune-inflammatory and malignant conditions.

Interferon alfa-2b is the only interferon that has been approved by the FDA for the treatment of multiple myeloma as maintenance therapy with prednisone however, there is a limited survival benefit.

Drug Name Interferon alfa-2b
Trade Name Intron A
Company Name Manufactures at Biogen, marketed by Schering-Plough
Date of Approval March 29, 2011

Uses of Interferon alfa-2b:

Hairy cell leukemia, malignant melanoma, and Kaposi’s sarcoma linked to AIDS are all treated with this medication.

20% of individuals with previously treated multiple myeloma can experience remissions after receiving INTRON A. [ref]

Mechanism of action of Interferon alfa-2b:

When interferon alpha interacts to type I interferon receptors, two Janus kinase tyrosine kinases are activated. These phosphorylate the receptors and transphosphorylate themselves.

When Stat1 and Stat2 (signal transducers and activators of transcription) connect to the phosphorylated INFAR receptors, various (around 100) immunomodulatory and antiviral proteins are activated.

Compared to interferon beta, interferon alpha binds to type I interferon receptors less stably.

Major Contraindications

  • Autoimmune hepatitis
  • Hypersensitivity
  • Decompensated liver disease (Child-Pugh >6 [class B and C])
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Immunosuppressants to treat Multiple Myeloma:

The three FDA-approved immunosuppressants which have got FDA approval for the treatment of Multiple Myeloma are discussed here.

These drugs are very commonly used usually in combination with other agents such as Bortezomib and Dexamethasone.

Immunosuppressants approved for the treatment of Multiple Myeloma

Generic Name Brand Name Date of Approval
Thalidomide Thalomid July 16, 1998 [ref]
Lenalidomide Revlimid February 22, 2017 [ref]
Pomalidomide Imnovid, Pomalyst February 8, 2013 [ref]

Thalidomide (Thalomid) is one of the most commonly used chemotherapeutic immunosuppressive drugs used to treat patients with multiple myeloma.

It is administered with other potent drugs in various combination regimens that include:

  • Bortezomib, thalidomide, and dexamethasone
  • Daratumumab, bortezomib, thalidomide, and dexamethasone
  • Dexamethasone, thalidomide, Cisplatin, Doxorubicin, Cyclophosphamide, Etoposide, Bortezomib (VTD-PACE)
Drug Name Thalidomide
Trade Name Thalomid
Company Name Chemie Grünenthal GmbH
Date of Approval July 16, 1998 [ref]

Uses of Thalidomide:

Thalidomide has been approved for use by the American Food and Drug Administration (FDA) to treat specific types of leprosy complications since July 16, 1998.

Its usage has been approved for multiple myeloma patients since October 26, 2006.

Mechanism of action of Thalidomide:

TNF-alpha is suppressed, and cell surface adhesion molecules important for leukocyte movement are downregulated.

Inhibiting angiogenesis may be the cause of anticancer action.

Major Contraindications

Hypersensitivity, Pregnancy (extremely teratogenic)

Lenalidomide (Revlimid) has almost replaced thalidomide as one of the first-line drugs in treating multiple myeloma.

It is used as one of the most potent drugs in various treatment regimens:

  • Bortezomib, Lenalidomide, Dexamethasone
  • Carfilzomib, Lenalidomide, Dexamethasone
  • Daratumumab, Lenalidomide, Bortezomib, Dexamethasone
  • Ixazomib, Lenalidomide, Dexamethasone
  • Cyclophosphamide, Lenalidomide, Dexamethasone
Drug Name Lenalidomide
Trade Name Revlimid
Company Name Bristol-Myers Squibb Company; Celgene Corporation.
Date of Approval February 22, 2017 [ref]

Uses of Lenalidomide:

REVLIMID is a prescription drug that is given to persons with multiple myeloma as a maintenance therapy following autologous hematopoietic stem cell transplantation or in conjunction with the drug dexamethasone.

Mechanism of action of Lenalidomide:

Thalidomide analog that is immunomodulatory, antiangiogenic, and suppresses the release of pro-inflammatory cytokines also boosts cell-mediated immunity by promoting the growth of anti-CD3 activated T cells.

Major Contraindications

Pregnancy and the lack of use of two types of contraception by sexually active women who are of reproductive age

Evidence of hypersensitivity (eg, angioedema, Stevens-Johnson syndrome, toxic epidermal necrolysis)

Pomalidomide is a thalidomide analog. It is an FDA-approved drug indicated for the treatment of patients with Multiple Myeloma who have been treated previously with two or more treatment regimens that included Bortezomib and Lenalidomide [Ref].

The Eloquent-3 Trial evaluated Pomalidomide and Dexamethasone with Elotuzumab, Pomalidomide, and Dexamethasone.

The overall response rate was 53% in the triple combination therapy vs 26% in the Pomalidomide and Dexamethasone group [Ref].

Drug Name Pomalidomide
Trade Name Imnovid, Pomalyst
Company Name Celgene Corporation
Date of Approval February 8, 2013 [ref]

Uses of Pomalidomide:

Pomalidomide is recommended for multiple myeloma patients who have had at least two previous treatments, including lenalidomide, and have shown disease progression on or within 60 days after finishing the last treatment.

KS in HIV-negative people as well as KS in AIDS patients who have failed highly active antiretroviral therapy (HAART) are also approved for treatment with this drug.

Mechanism of action of Pomalidomide:

Thalidomide analog with immunomodulatory and anti-cancer effects that suppresses hematopoietic tumor cell growth and induces apoptosis.

Additionally, it boosts T-cell and natural killer cell-mediated immunity inhibits the generation of TNF-alpha and interleukin-6, and downregulates leukocyte migration-related cell surface adhesion molecules.

Inhibiting angiogenesis may be the cause of anticancer action.

Major Contraindications:

  • Pregnancy
  • Hypersensitivity to the drug or excipients
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Anti-BCMA Antibodies for the treatment of Multiple Myeloma:

Two of the most latest FDA-Approved drugs for the treatment of Multiple Myeloma belong to the class of drugs called Anti-BCMA Antibodies.

Anti-BCMA Antibodies target BCMA Antigens (B-cell maturation antigen) which is expressed in a variety of neoplastic and plasma cells.

Anti-BCMA Antibodies for the treatment of Multiple Myeloma:

Generic Name Brand name Date of Approval
Belantamab mafodotin BLENREP August 5, 2020 [ref]
Teclistamab Tecvayli October 25, 2022 [ref]

Belantamab mafodotin is approved as monotherapy for the treatment of patients with multiple myeloma who have failed four prior treatments.

It is indicated in patients who have failed four prior treatments, who are refractory to the following treatments, and who show disease progression:

  • at least one immunomodulatory agent
  • at least one proteasome inhibitor, and
  • an anti-CD-38 antibody

Belantamab mafodotin is only available through a restricted program under a risk evaluation and mitigation program [Ref].

Drug Name Belantamab mafodotin
Trade Name BLENREP
Company Name GlaxoSmithKline
Date of Approval August 5, 2020 [ref]

Uses of Belantamab mafodotin:

Adults who have multiple myeloma that has relapsed or become resistant to therapy and who have had at least four previous treatments, including an anti-CD38 monoclonal antibody, a proteasome inhibitor, and an immunomodulatory drug, should be treated with Belantamab mafodotin.

Mechanism of action of Belantamab mafodotin:

This is an afucosylated monoclonal antibody that attacks B cell maturation antigen (BCMA), which is coupled to the microtubule disruptor monomethyl auristatin-F (MMAF).

Afucosylation of monoclonal antibodies’ Fc regions improves binding to the Fc region, which improves antibody-dependent cell-mediated cytotoxicity.

On CD138-positive myeloma cells, BCMA is only expressed. Delivering MMAF to multiple myeloma cells with great specificity is made possible by Belantamab mafodotin’s targeting of BCMA.

After internalization into cells and binding to BCMA, Belantamab mafodotin releases MMAF.

Apoptosis is the outcome of the MMAF payload binding to tubulin and arresting the cell cycle at the DNA damage checkpoint between the G2 and M phases.

Major Contraindications

Blenrep is not recommended for usage during pregnancy because it might damage a growing fetus.

Before you begin Blenrep therapy, your doctor will do a pregnancy test to see if you are capable of getting pregnant.

Females should use a reliable method of birth control during their therapy and for four months after finishing the medication.

Teclistamab (Tecvayli) is another anti-BCMA ADC antibody. It binds to CD-3 positive T Cells and BCMA receptors that are expressed on the surface of myeloma cells.

It got accelerated approval in October 2022 for the treatment of super-refractory multiple myeloma. It is indicated if the patient has a poor response to four prior treatment regimens and show disease progression despite therapy.

Teclistamab is indicated in patients who have not received anti BCMA therapy before and are refractory to at least:

  • One Proteasome inhibitor
  • an immune-modulatory agent, and
  • anti-CD-38 antibody.
Drug Name Teclistamab
Trade Name Tecvayli
Company Name Janssen Pharmaceutical Companies
Date of Approval October 25, 2022 [ref]

Uses of Teclistamab:

 it is indicated in the treatment of multiple myeloma

Mechanism of action of Teclistamab:

Bispecific T-cell engaging antibody binds to BCMA, which is expressed on the surface of some healthy B-lineage cells, and the CD3 receptor on the surface of T cells and multiple myeloma cells.

Major Contraindications

None
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CAR T-Cell Therapy for the treatment of Multiple Myeloma:

CAR T-Cell therapy is one of the latest advancements in treating cancers and immunologic disorders. CAR-T cells (chimeric antigen receptors) are drug conjugates that are highly targeted and have shown superiority to most conventional treatments.

These drugs are usually indicated in patients who have failed to respond to the previous four or more therapies.

CAR T-Cell Therapies

Generic Name Brand name Date of Approval
Idecabtagene vicleucel Abecma March 27, 2021 [ref]
Ciltacabtagene autoleucel Carvykti February 28, 2022 [ref]

Idecabtagene vicleucel is an anti-BCMA-directed genetically modified CAR-T Cell (Chimeric antigen receptor T cell) therapy.

It is indicated in patients with refractory multiple myeloma who have failed at least four previous therapies that included:

  • a proteasome inhibitor
  • an immunomodulatory agent
  • anti-CD-38 antibody
Drug Name Idecabtagene vicleucel
Trade Name Abecma
Company Name Bristol Myers Squibb
Date of Approval March 27, 2021 [ref]

Uses of Abecma:

ABECMA (Idecabtagene vicleucel) is a medication that is only available by prescription and is used to treat multiple myeloma in individuals who have tried at least four different treatment regimens that have either failed or ceased functioning.

Mechanism of action of Abecma

In the malignancy known as multiple myeloma, plasma cells multiply uncontrollably and quickly. The B-cell maturation antigen is frequently expressed on malignant cells but is infrequently expressed on non-cancerous cells.

An anti-B-cell maturation antigen scFv-targeting domain, a CD3 T-cell activation domain, and a 4-1BB costimulatory domain are all present in the chimeric antigen receptor of idecabtagene vicleucel.

The single chain variable fragment (scFv) enables the CAR’s antigen selectivity for B-cell maturation.

T-cell activation is mediated by CD2, a T-cell surface adhesion protein, through the CD23 cytoplasmic domain. Interferon- production and cytotoxic T-cell activity are both improved by 4-1BB.

Idecabtagene vicleucel binds to cells that express the B-cell maturation antigen. After binding to the target, Idecabtagene vicleucel multiplies, cytokines are secreted, and the targeted cells are destroyed.

Major Contraindications

Significant adverse effects (particularly pulmonary, cardiac, or hypotension-related ones) that have not been adequately addressed, including those following prior chemotherapy.

Aggressive inflammatory diseases or illnesses

Ciltacabtagene autoleucel is another drug that got approval very recently. It is a BCMA-CAR-T cell-directed therapy.

It is indicated in patients with refractory multiple myeloma who have failed at least four previous therapies that included:

  • a proteasome inhibitor
  • an immunomodulatory agent
  • anti-CD-38 antibody

It got approval when patients in the CARTITUDE-1 study showed almost 98% response with 78% of the patients achieving a complete response [Ref].

Drug Name Ciltacabtagene autoleucel
Trade Name Carvykti
Company Name Janssen Biotech, Inc
Date of Approval February 28, 2022 [ref]

Uses of Ciltacabtagene autoleucel

Used to treat multiple myeloma in individuals who have had therapy with at least four prior anticancer medicines but the disease has returned or has not improved.

Mechanism of action of Ciltacabtagene autoleucel

It entails reprogramming a patient’s own T cells with a transgene encoding a CAR that recognizes and destroys cells that express BCMA. This is a BCMA-directed, genetically altered autologous T-cell immunotherapy.

Major Contraindications

None
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Selective Inhibitors of Nuclear Export for the treatment of Multiple Myeloma:

Selective Inhibitors of Nuclear Export are drugs that target tumor suppressor proteins, growth regulators, and expoportin-1.

These drugs are indicated in combination with Dexamethasone and should only be used if a person has failed four prior treatment regimens.

Selective Inhibitors of Nuclear Export

Generic Name Brand name Date of Approval
Selinexor Xpovio December 18, 2020 [ref]

Selinexor belongs  to the class of drugs called SINE (Selective inhibitor of Nuclear Export). It is approved for the treatment of patients with refractory multiple myeloma who have failed 4 or more therapies in the past that included:

  • 2 or more proteasome inhibitors
  • 2 or more immunomodulatory drugs, and
  • anti-CD38 antibody.

It is recommended in combination with Dexamethasone.

Drug Name Selinexor
Trade Name Xpovio
Company Name Karyopharm Therapeutics
Date of Approval December 18, 2020 [ref]

Uses of Selinexor:

Selinexor is used to treat individuals with multiple myeloma who have a poor response to four or more previous therapies including at least 2 immunomodulatory drugs, 2 proteasome inhibitors, and an anti-CD-38 antibody.

Mechanism of action of Selinexor:

Xpovio inhibits (blocks) the activity of the XPO1 protein once it has attached to its target. As a result, the cancer cells gradually perish.

The first targeted medicine with this particular mode of action to receive FDA approval is Xpovio.

Major Contraindications

None
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FDA-Approved Bisphosphonates for the treatment of Multiple Myeloma:

Bisphosphonates are used to treat patients with multiple myeloma who have bone disease. Bone disease can manifest as bone pains, lytic lesions, and pathological fractures.

Bisphosphonates for Multiple Myeloma:

Generic Name Brand name Date of Approval
Pamidronate Aredia, Pamisol September 22, 1998 [ref]
Zoledronic acid Aclasta, Reclast, Zometa February 22, 2002 [ref]

Pamidronic Acid is a potent bisphosphonate. It is administered as a once-monthly infusion administered over four hours.

It can markedly reduce skeletal pains and reduce the risk of pathological fractures.

Drug Name Pamidronic acid
Trade Name Aredia, Pamisol
Company Name Novartis Pharmaceuticals Corporation
Date of Approval September 22, 1998 [ref]

Uses of Pamidronic acid:

Aredia is prescribed to treat moderate to severe osteolytic bone metastases from breast cancer, moderate to severe Paget’s disease of the bones, moderate to severe hypercalcemia of malignancy, and moderate to severe osteolytic lesions from multiple myeloma.

Mechanism of action of Pamidronic acid:

Bisphosphonates enter the bone and attach to hydroxyapatite there. Osteoclasts break down bone, which results in local acidity and the release of bisphosphonate, which is then taken up by the osteoclast by fluid-phase endocytosis.

Osteoclasts‘ cytosol is where bisphosphonates operate once endocytic vesicles get acidified.

Bone resorption is mediated by osteoclasts. Osteoclasts create F-actin ring structures called podosomes when they adhere to the bone.

Osteoclasts don’t separate from bones when the podosomes are disrupted, which stops bone resorption.

Bisphosphonates that include nitrogen, like pamidronate, are known to cause hematopoietic malignancy cells to undergo apoptosis by blocking the mevalonate pathway enzymes farnesyl diphosphate synthase, farnesyl diphosphate, and geranylgeranyl diphosphate.

These elements are necessary for Rap1 and other GTP-binding proteins to be prenylated post-translationally.

These proteins’ absence of prenylation affects how they work and, in the case of Rap1, causes apoptosis.

Caspases 3 and 9 were also triggered by pamidronate, adding to the process of apoptosis.

Major Contraindications:

Aredia is contraindicated in the following cases

  • thyroid gland surgery.
  • low blood levels of magnesium.
  • blood phosphate levels are low.
  • blood calcium levels are low.
  • Dehydration
  • low potassium levels in the blood.
  • inflammation of the gums and bone around a tooth
  • reduced kidney performance

Zoledronic acid is a very potent bisphosphonate. It is administered every 3 to 4 weeks in patients with multiple myeloma and bone disease.

It markedly reduces bony pains and the risk of fractures in patients with multiple myeloma.

Drug Name Zoledronic acid
Trade Name Aclasta, Reclast, Zometa
Company Name Novartis
Date of Approval February 22, 2002 [ref]

Uses of Zoledronic Acid:

This drug is used to treat hypercalcemia, a condition that can develop in cancer patients.

In addition to chemotherapy, zoledronic acid is used to address bone issues that may arise from multiple myeloma and other cancers (such as breast and lung cancer) that have progressed to the bones.

Mechanism of action of Zoledronic Acid:

Inhibition of bone resorption is the main pharmacologic effect of zoledronic acid.

Multiple components are believed to have a role in this activity, despite the fact that the antiresorptive mechanism has yet to be totally discovered.

Zoledronic acid reduces osteoclast activity and triggers osteoclast apoptosis in culture.

Major Contraindications

All indications point to Intolerance, including infrequent occurrences of urticaria, angioedema, and  anaphylactic shock

Non-cancer applications: Hypocalcemia, acute renal impairment, or severe renal impairment (CrCl less than 35 mL/min)

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Colony Stimulating Factors:

Colony Stimulating Factors are used for the correction of anemia and cytopenias in patients with multiple myeloma.

Colony Stimulating Factors

Generic Name Brand name Date of Approval
Epoetin alfa Abseamed, Epoetin Alfa Hexal, Epogen, Eporatio, Epprex, Eprex, Procrit, Retacrit, Silapo April 1, 1993 [ref]

Erythropoietin, like bisphosphonates, is used only symptomatically. It is indicated for the treatment of anemia associated with multiple myeloma.

Drug Name Erythropoietin
Trade Name Abseamed, Epoetin Alfa Hexal, Epogen, Eporatio, Epprex, Eprex, Procrit, Retacrit, Silapo
Company Name Amgen Inc, ​​Janssen Biotech
Date of Approval April 1, 1993 [ref]

Uses of Erythropoietin:

It helps the body produce more red blood cells, thereby treating anemia.

Mechanism of action of Erythropoietin:

Epoetin alfa stimulates the production of red blood cells in the bone marrow. This drug is remarkably similar to the erythropoietin that your body naturally produces to treat anemia.

Major Contraindications

  • Hypersensitivity to products generated from mammalian cells, albumin, or epoetin alfa
  • Patients with cancer whose anemia is brought on by causes other than chemotherapy
  • Uncontrollable hypertension
  • Pure red-cell aplasia that develops upon administration of any erythropoietin protein medications
  • Use of benzyl alcohol-containing multidose vials in young children, newborns, or women who are expecting or nursing

What do you think?

Written by Ahmed Farhan

I am an Internist practicing medicine for the last fifteen years. Over the years, I have learned that medicine is not about prescribing pills. True medical practice is helping people.
I do prescribe pills as well but the best results I get are when I motivate people to overcome their problems with little changes in their lifestyles.
Since most of my patients are obese and have diabetes, hypertension, and high cholesterol levels, I am writing at dibesity.com when free.
Dibesity, I know the correct word is diabesity. Ignore this! Be with us.
Also, you can contact me directly at dibesity.com@gmail.com

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