13 targeted therapies for Multiple Myeloma(MM)

Date:2023-03-28 Views: 259 Times
Longevity/Anti-cancer

The main targeted drugs for multiple myeloma(MM). Targeted therapy drugs work by targeting specific proteins or processes in cancer cells while causing less damage to normal cells.Some targeted drugs used for multiple myeloma include:

Proteasome inhibitors

These drugs inhibit the protein complex called proteasome, which is responsible for degrading unwanted proteins in cells. By inhibiting proteasome, these drugs disrupt multiple cellular processes, leading to cell death. Examples of proteasome inhibitors used in multiple myeloma treatment include:

Bortezomib[1]

The initial FDA approval of bortezomib was in 2003 for the treatment of patients with myeloma.

In 2014, the FDA approved bortezomib (Velcade; Millennium Pharmaceuticals [Takeda]) for 2 new indications. On August 8, 2014, bortezomib was approved for the retreatment of adult patients with myeloma whose disease had previously responded to bortezomib therapy and relapsed at least 6 months after the completion of that therapy with bortezomib.

Approval Statushttps://www.accessdata.fda.gov/drugsatfda_docs/nda/2003/21602_Velcade.cfm#:~:text=Approval%20Date%3A%205%2F13%2F2003
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/velcade-bortezomib-342256
Stage: clinical developmenthttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4665054/
REFERENCE

Carfilzomib[2]

Dec. 1, 2021.FDA Approves New KYPROLIS® (carfilzomib) Combination Regimen With DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) and dexamethasone For Patients With Multiple Myeloma At First Or Subsequent Relapse.

Approval Statushttps://www.amgen.com/newsroom/press-releases/2021/12/fda-approves-new-kyprolis-carfilzomib-combination-regimen-with-darzalex-faspro-daratumumab-and-hyaluronidasefihj-and-dexamethasone-for-patients-with-multiple-myeloma-at-first-or-subsequent-relapse
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/kyprolis-carfilzomib-999762
Stage: clinical developmenthttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5013842/
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Ixazomib[3]

Ixazomib (Ninlaro(®)) is an orally bioavailable, reversible proteasome inhibitor developed by Millennium Pharmaceuticals, Inc. (now Takeda Oncology). Ixazomib acts by binding to and inhibiting the β5 subunit of the 20S proteasome. In November 2015, the US FDA approved ixazomib for use in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. 

Approval Statushttps://pubmed.ncbi.nlm.nih.gov/26846321/
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/ninlaro-ixazomib-1000064
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/ixazomib
REFERENCE

Immunomodulatory drugs (IMiDs)

These drugs modulate the immune system and have multiple effects on cancer cells, including promoting their death, inhibiting their growth, and preventing blood vessels from forming around tumors. Examples of IMiDs used for multiple myeloma include:

Thalidomide[4]

In the 1950s and 1960s, thalidomide was used to treat morning sickness during pregnancy. But it was found to cause disabilities in the babies born to those taking the drug. Now, decades later, thalidomide (Thalomid) is being used to treat a skin condition and cancer.

Approval Statushttps://www.news-medical.net/health/History-of-Thalidomide.aspx
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/thalomid-thalidomide-343211
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/thalidomide
REFERENCE

Lenalidomide[5]

In 2006, lenalidomide, an orally administered thalidomide analogue, received FDA approval for use with dexamethasone in patients with multiple myeloma who received at least one prior therapy. In 2015, the indication was expanded for use in combination with dexamethasone for the treatment of patients with multiple myeloma, to include newly diagnosed multiple myeloma patients who are not eligible for autologous stem cell transplant. Lenalidomide is also approved in myelodysplastic syndromes and mantle cell lymphoma.

Approval Statushttps://www.fda.gov/drugs/resources-information-approved-drugs/lenalidomide-revlimid#:~:text=In%202006%2C%20lenalidomide%2C%20an%20orally,at%20least%20one%20prior%20therapy.
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/revlimid-lenalidomide-342200
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/lenalidomide
REFERENCE

Pomalidomide[6]

On February 8, 2013, the FDA approved pomalidomide (Pomalyst; Celgene), the most recent IMiD, for the treatment of patients with MM who have received at least 2 previous therapies, including lenalidomide and bortezomib, and have demonstrated disease progression within 60 days of the completion of the last therapy.

Approval Statushttps://www.drugs.com/history/pomalyst.html
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/pomalyst-pomalidomide-999809
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/pomalidomide
REFERENCE

Histone deacetylase (HDAC) inhibitors

These drugs inhibit histone deacetylase enzymes, which are involved in regulating gene expression. Inhibiting these enzymes can lead to changes in gene expression that promote cancer cell death. An example of an HDAC inhibitor used for multiple myeloma is:

Panobinostat[7]

On February 23, 2015, the US Food and Drug Administration (FDA) approved panobinostat (Farydak; Novartis Pharmaceuticals), an orally administered inhibitor of histone deacetylase (HDAC), for the treatment of patients with multiple myeloma who have received at least 2 previous regimens, including bortezomib and an immunomodulatory agent.

Approval Statushttps://www.drugs.com/history/farydak.html
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/farydak-panobinostat-1000004
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/panobinostat
REFERENCE

Selective Inhibitor of Nuclear Export (SINE)

Selective inhibitors of nuclear export (also called SINEs or SINE compounds) are molecules that bind to XPO1 and inhibit it, thereby blocking the export of tumor suppressor proteins from the nucleus. Blocking XPO1 means that tumor suppressors accumulate in the nucleus and can kill cancerous cells.

Selinexor[8]

Selinexor is a first-in-class, oral Selective Inhibitor of Nuclear Export (SINE) compound. Selinexor functions by binding with, and inhibiting, the nuclear export protein, XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to lead to the selective induction of apoptosis in cancer cells, while largely sparing normal cells.

Approval Statushttps://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-selinexor-refractory-or-relapsed-multiple-myeloma
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/xpovio-selinexor-1000301
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/selinexor
REFERENCE

Monoclonal antibodies

These are lab-made proteins designed to recognize and bind to specific proteins on cancer cells, leading to an immune response against the cancer cells or interfering with their growth. Examples of monoclonal antibodies used for multiple myeloma include:

Daratumumab[9]

On November 30, 2021, the Food and Drug Administration approved daratumumab + hyaluronidase-fihj (Darzalex Faspro, Janssen Biotech, Inc.) and carfilzomib (Kyprolis, Amgen, Inc.) plus dexamethasone for adult patients with relapsed or refractory multiple myeloma who have received 1 to 3 prior lines of therapy.

Approval Statushttps://www.fda.gov/drugs/resources-information-approved-drugs/daratumumab-darzalex
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/darzalex-daratumumab-1000063
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/daratumumab
REFERENCE

Elotuzumab[10]

The FDA approved elotuzumab in November 2015 for use in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who received 1 to 3 prior therapies.

Approval Statushttps://www.drugs.com/history/empliciti.html
Instructions for use:dosing, indications, interactions...etc.https://www.sciencedirect.com/topics/medicine-and-dentistry/elotuzumab
Stage: clinical developmenthttps://reference.medscape.com/drug/empliciti-elotuzumab-1000066
REFERENCE

Isatuximab[11]

On March 31, 2021, the FDA approved isatuximab-irfc (brand name Sarclisa) in combination with carfilzomib and dexamethasone, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.

Approval Statushttps://www.fda.gov/drugs/resources-information-approved-drugs/fda-disco-burst-edition-fda-approval-sarclisa-isatuximab-irfc-combination-carfilzomib-and#:~:text=On%20March%2031%2C%202021%2C%20the,three%20prior%20lines%20of%20therapy.
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/sarclisa-isatuximab-4000022
Stage: clinical developmenthttps://www.sciencedirect.com/topics/medicine-and-dentistry/isatuximab
REFERENCE

BCMA-targeted therapy

B-cell maturation antigen (BCMA) is a protein found on the surface of multiple myeloma cells. Some drugs are designed to target BCMA, such as:

Belantamab mafodotin[12]

Belantamab mafodotin was granted accelerated approval for the treatment of adult patients with RRMM who have received at least four prior therapies including an anti-CD38 mAb, a PI, and an IMID.

Approval Statushttps://www.fda.gov/drugs/resources-information-approved-drugs/fda-granted-accelerated-approval-belantamab-mafodotin-blmf-multiple-myeloma
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/blenrep-belantamab-mafodotin-4000056
Stage: clinical developmenthttps://www.sciencedirect.com/science/article/abs/pii/S2152265022002555
REFERENCE

Teclistamab-cqyv[13]

On October 25, 2022, the Food and Drug Administration granted accelerated approval to teclistamab-cqyv (Tecvayli, Janssen Biotech, Inc.), the first bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager, for adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.

Approval Statushttps://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-teclistamab-cqyv-relapsed-or-refractory-multiple-myeloma
Instructions for use:dosing, indications, interactions...etc.https://reference.medscape.com/drug/tecvayli-teclistamab-4000281
Stage: clinical developmenthttps://www.sciencedirect.com/science/article/abs/pii/S2152265023000617
REFERENCE

Please note that this list may not be exhaustive and the treatment options for multiple myeloma continue to evolve. Consult a healthcare professional for the most up-to-date information and personalized advice on multiple myeloma treatment.


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