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Hodgkins Lymphoma Treatment: List of Drugs

Hodgkins Lymphoma Treatment

Hodgkins lymphoma treatment

Hodgkins Lymphoma Treatment has not changed much over time except for the addition of a few latest FDA-approved drugs.

Treatment of Hodgkin’s Lymphoma includes:

  • Radiation therapy
  • Induction chemotherapy
  • Salvage Therapy, and
  • Hematopoietic stem cell transplantation

We’ll focus on all the drugs that are used to treat patients with Hodgkin’s Lymphoma.

FDA-approved Drugs to treat Hodgkin’s Lymphoma:

Drugs to treat Hodgkin’s Lymphoma

Generic Name

Antineoplastic Alkylating Agents Mechlorethamine
Antineoplastic Antibiotic Bleomycin
Antineoplastic Vinca Alkaloid Vinblastine
Dacarbazine
Vincristine
Antineoplastic Podophyllotoxin Derivatives Etoposide
Procarbazine
Antineoplastic Alkylating DMARDs, Immunomodulators Cyclophosphamide
Antineoplastic Anthracyclines Doxorubicin
Antineoplastic Antimicrotubular Brentuximab Vedotin
Corticosteroids Prednisone
PD-1/PD-L1 Inhibitors Nivolumab
Pembrolizumab

The three latest FDA-approved drugs for Hodgkin’s Lymphoma are primarily reserved for those patients who have a refractory course of illness and those who have relapsed after hematopoietic stem cell transplantation.

However, Brentuximab Vedotin (Adcetris) has replaced Bleomycin in the ABVD induction chemotherapy which is now called A+AVD.

Latest Approved Drugs for HL Generic name Date of Approval
Antineoplastic Antimicrotubular Brentuximab Vedotin November 2022
PD-1/ PD-L1 Inhibitors Nivolumab March 2022
Pembrolizumab March 2017
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Hodgkins Lymphoma Treatment List:

Mechlorethamine is a very toxic drug. It is one of the components of the MOPP regimen for the treatment of Hodgkin’s Lymphoma:

MOPP regimen:

  • Mechlorethamine,
  • Vincristine [Oncovin],
  • Procarbazine,
  • Prednisone
Generic name: Mechlorethamine
Trade name: Mustargen, mechlorethamine HCl, Nitrogen Mustard, Valchlor
Company name: Recordati Rare Diseases
Date of approval: 1949?
MOA It causes the creation of carbonium ions, which inhibits DNA and RNA synthesis; crosslinks DNA strands (interstrand and intrastrand crosslinking), which results in miscoding breakage and ultimately fails DNA replication.
Uses For the therapy of chronic myelocytic or chronic lymphocytic leukemia, mycosis fungoides, bronchogenic carcinoma, Hodgkin’s disease (Stages III and IV), and ​​polycythemia vera.
Contraindications Active infections, hypersensitivity, and any history of anaphylaxis.
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Bleomycin (Blenoxane) is another drug that has been used for years for the treatment of Hodgkin’s Lymphoma.

It is one of the ingredients of the three commonly used regimens:

  • ABVD:
    • Doxorubicin (Adriamycin),
    • Bleomycin,
    • Vinblastine,
    • Dacarbazine
  • Stanford V:
    • Doxorubicin,
    • Vinblastine,
    • Mustard,
    • Bleomycin,
    • Vincristine,
    • Etoposide,
    • Prednisone
  • BEACOPP:
    • Bleomycin,
    • Etoposide,
    • Doxorubicin,
    • Cyclophosphamide,
    • Vincristine,
    • Procarbazine,
    • Prednisone

Bleomycin is associated with severe pulmonary toxicity. Because of the lung-associated side effects, bleomycin has been replaced by Brentuximab vedotin (Adcetris) in the ABVD regimen.

Generic name: Bleomycin
Trade name: Blenoxane
Company name: Bristol Laboratories
Date of approval: June 3, 1996 [ref]
MOA Despite the fact that the precise method of action of bleomycin is unknown, the information that is now available would appear to suggest that the major mode of action is the inhibition of DNA synthesis, with some indication of a weaker inhibition of RNA and protein synthesis.

Bleomycin’s DNA-cleaving abilities are reliant on oxygen and metal ions, as shown by in vitro investigations.

Bleomycin is thought to bind metal ions, particularly iron, and create a pseudoenzyme that interacts with oxygen to create free radicals called superoxide and hydroxide, which break DNA.

Uses Bleomycin is used to treat testicular cancer, ovarian cancer, cervical cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, and others.
Contraindications Bleomycin and brentuximab should not be used together due to pulmonary toxicity, Hypersensitivity.
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Vinblastine (Velban) is one of the oldest drugs still used to treat certain cancers. Vinblastine is a part of the three commonly used regimens:

  • ABVD:
    • Doxorubicin (Adriamycin),
    • Bleomycin,
    • Vinblastine,
    • Dacarbazine
  • A+AVD:
    • Brentuximab Vedotin (Adcetris),
    • Doxorubicin,
    • Vinblastine,
    • Dacarbazine
  • Stanford V:
    • Doxorubicin,
    • Vinblastine,
    • Mustard,
    • Bleomycin,
    • Vincristine,
    • Etoposide,
    • Prednisone
Generic name: Vinblastine
Trade name: Velban
Company name:
Date of approval: November 25, 1965 [ref]
MOA Vinblastine is believed to suppress mitosis at metaphase through its interaction with tubulin, which accounts for the majority of its anticancer effect.

Vinblastine crystallizes microtubules and causes mitotic arrest or cell death when it attaches to the mitotic spindle’s microtubular proteins.

Uses Used to treat mycosis fungoides, Kaposi’s sarcoma, Hodgkin’s and non-Hodgkin’s lymphomas, breast cancer, lymphomas, testicular cancer, and neuroblastoma.
Contraindications
  • Active bacterial infection
  • Intrathecal (IT) administration
  • Myelosuppression
  • Hypersensitivity
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Dacarbazine is a cytotoxic non-cell-cycle specific drug indicated for the treatment of Hodgkin’s Lymphoma.

It is one of the components of the two commonly used induction regimens:

  • ABVD:
    • Doxorubicin (Adriamycin)
    • Bleomycin,
    • Vinblastine,
    • Dacarbazine
  • A+AVD:
    • Brentuximab Vedotin (Adcetris),
    • Doxorubicin,
    • Vinblastine,
    • Dacarbazine
Generic name: Dacarbazine
Trade name:  DTIC Dome
Company name: Bayer
Date of approval: May 1975 [ref]
MOA Although the exact mechanism of action is unknown, it appears that its function as an alkylating agent causes cytotoxic consequences.

Other hypotheses include interactions with SH groups and DNA synthesis inhibition due to its purine analogous effect.

There is no cell cycle phase distinction in dacarbazine.

Uses To treat malignant melanoma that has spread throughout the body.

When combined with other antineoplastic medicines, dacarbazine is also recommended for Hodgkin’s disease as a secondary-line treatment.

Contraindications Severe anemia, Breastfeeding, Hypersensitivity, and severe thrombocytopenia.
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Vincristine (Vincasar PFS, Oncovin) is one of the most potent and active chemotherapeutic drugs used to treat a variety of cancers including ALL, Hodgkins Lymphoma, Non-Hodgkin’s Lymphoma, Ovarian, small cell lung cancer, and Ewing sarcoma.

In the treatment of Hodgkin’s Lymphoma, it is a component of the following regimens:

  • MOPP:
    • Mechlorethamine,
    • Vincristine (Oncovin),
    • Procarbazine,
    • Prednisone
  • Stanford V:
    • Doxorubicin,
    • Vinblastine,
    • Mustard,
    • Bleomycin,
    • Vincristine,
    • Etoposide,
    • Prednisone
  • BEACOPP:
    • Bleomycin,
    • Etoposide,
    • Doxorubicin,
    • Cyclophosphamide,
    • Vincristine,
    • Procarbazine,
    • Prednisone
Generic name: Vincristine
Trade name: Marqibo, Vincasar, Vincasar PFS, Oncovin
Company name: Eli Lilly Company
Date of approval: 1963. Liposomal Vincristine on August 9, 2012 [ref]
MOA 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.

Uses Brain tumors, small cell lung cancer, Wilms’ tumor, neuroblastoma, sarcomas, Hodgkin disease, AML, CML.
Contraindications
  • Hypersensitivity
  • Intrathecal (IT) administration
  • Charcot-Marie-Tooth syndrome (demyelinating form)
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Etoposide (Toposar) is used in the treatment of the following regimens:

  • Stanford V:
    • Doxorubicin,
    • Vinblastine,
    • Mustard,
    • Bleomycin,
    • Vincristine,
    • Etoposide,
    • Prednisone
  • BEACOPP:
    • Bleomycin,
    • Etoposide,
    • Doxorubicin,
    • Cyclophosphamide,
    • Vincristine,
    • Procarbazine,
    • Prednisone
  • ICE:
    • Ifosfamide,
    • Carboplatin,
    • Etoposide
  • ESHAP:
    • Etoposide,
    • Methylprednisolone,
    • Cytarabine,
    • Cisplatin
Generic name: Etoposide
Trade name: Etopophos, Toposar, Vepesid
Company name: Jiangsu Hengrui, Nippon Kayaku
Date of approval: 1983 [ref]
MOA By combining topoisomerase II and DNA to create a complex, etoposide prevents the synthesis of DNA. By interacting with topoisomerase II, this complex causes double-stranded DNA to break and hinders their repair.

DNA damage over time prevents cells from entering the mitotic phase of cell division, which results in cell death.

Uses For use as the first line of therapy in individuals with small-cell lung cancer and in the treatment of resistant testicular cancers when combined with other chemotherapeutic drugs.

It is used to treat glioblastoma multiforme, lymphoma, and non-lymphocytic leukemia, among other cancers.

Contraindications Hypersensitivity to etoposide or teniposide
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Procarbazine (Matulane) is indicated for the treatment of Hodgkin’s Lymphoma. It is one of the components of the following regimens:

  • MOPP:
    • Mechlorethamine,
    • Vincristine (Oncovin),
    • Procarbazine,
    • Prednisone
  • BEACOPP:
    • Bleomycin,
    • Etoposide,
    • Doxorubicin,
    • Cyclophosphamide,
    • Vincristine,
    • Procarbazine,
    • Prednisone
Generic name: Procarbazine
Trade name: Matulane
Company name: Leadiant Biosciences.
Date of approval: July 22, 1969 (date not certain) [ref]
MOA Procarbazine inhibits the cell cycle during the S phase of cell division.

It is unclear exactly how procarbazine exerts its cytotoxic effects.

Procarbazine may also work by preventing the creation of proteins, RNA, and DNA.

Uses For the treatment of stage III and stage IV Hodgkin’s disease when combined with other anticancer medications.
Contraindications Hypersensitivity, leukopenia, Severe anemia, bone marrow depression, and thrombocytopenia.
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Cyclophosphamide (Cytoxan) is an immunosuppressant drug. It is commonly used to treat serious autoimmune rheumatic diseases such as vasculitis and nephritis.

In patients with Hodgkin’s Lymphoma, it is used as one of the components in the following regimen:

  • BEACOPP:
    • Bleomycin,
    • Etoposide,
    • Doxorubicin,
    • Cyclophosphamide,
    • Vincristine,
    • Procarbazine,
    • Prednisone
Generic name: Cyclophosphamide
Trade name: Procytox, Cytoxan
Company name: Baxter Oncology
Date of approval: August 17, 1999 [ref]
MOA Cyclophosphamide is a nitrogen mustard-type alkylating agent.

Phosphoramide mustard is a type of cyclophosphamide that has been activated, alkylates, or binds to DNA.

Cross-linking of DNA and RNA strands and the suppression of protein synthesis are the principal causes of its cytotoxic effects.

Uses It is used for the therapy of multiple myeloma, mycosis fungoides, malignant lymphomas, retinoblastoma, neuroblastoma, and adenocarcinoma of the ovary.
Contraindications
  • Hypersensitivity
  • Severe myelosuppression
  • Urinary outflow obstruction
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Doxorubicin (Adriamycin) is an anthracyclin that inhibits DNA synthesis by blocking the enzyme topoisomerase II.

It is one of the few drugs that is used in 4 of the commonly used regimens for Hodgkin’s Lymphoma.

  • ABVD:
    • Doxorubicin (Adriamycin),
    • Bleomycin,
    • Vinblastine,
    • Dacarbazine
  • A+AVD:
    • Brentuximab Vedotin (Adcetris),
    • Doxorubicin,
    • Vinblastine,
    • Dacarbazine
  • Stanford V:
    • Doxorubicin,
    • Vinblastine,
    • Mustard,
    • Bleomycin,
    • Vincristine,
    • Etoposide,
    • Prednisone
  • BEACOPP:
    • Bleomycin,
    • Etoposide,
    • Doxorubicin,
    • Cyclophosphamide,
    • Vincristine,
    • Procarbazine,
    • Prednisone
Generic name: Doxorubicin
Trade name: Adriamycin, Doxil, Myocet
Company name: Pfizer Inc.
Date of approval: November 17, 1995 [ref]
MOA Doxorubicin is thought to work in cancer cells by two different mechanisms: (I) intercalation into DNA, which interferes with topoisomerase-II-mediated DNA repair, and (II) production of free radicals, which cause damage to cellular membranes, DNA, and proteins.
Uses It is used for the therapy of ovarian carcinoma, bone sarcomas, malignant lymphoma, gastric carcinoma, thyroid carcinoma, acute myeloblastic leukemia, Hodgkin’s disease, neuroblastoma, etc.
Contraindications
  • Active infection
  • Hypersensitivity
  • Cardiomyopathy
  • Impaired cardiac function
  • severe myocardial insufficiency
  • A recent incident of MI
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Brentuximab vedotin (Adcetris) is one of the latest drugs approved for the treatment of Hodgkin’s Lymphoma.

It has replaced Bleomycin because of the pulmonary toxicity associated with it.

  • A+AVD:
    • Brentuximab Vedotin (Adcetris),
    • Doxorubicin,
    • Vinblastine,
    • Dacarbazine
Generic name: Brentuximab vedotin
Trade name: Adcetris
Company name: Takeda Pharmaceutical Company
Date of approval: November 10, 2022 [ref]
MOA A chimeric human-murine IgG1 that specifically targets CD30, monomethyl auristatin E (MMAE), a microtubule-disrupting substance, and a protease-susceptible linker that connects the antibody and MMAE make up the three components of the drug called Brentuximab vedotin.

Brentuximab vedotin can target tumor cells that have CD30 on their surface thanks to the IgG1 antibody.

Brentuximab vedotin then enters the cell. Once within, the linker is broken, releasing MMAE and binding to the microtubule network to cause disruption.

Chimeric IgG1 antibodies that are directed toward CD30 make up the drug’s antibody component.

A particle that disrupts microtubules is the tiny molecule MMAE.

A linker forms a covalent bond between the antibody and MMAE.

According to data, the binding of the ADC to CD30-expressing cells, internalization of the ADC-CD30 complex, and subsequent proteolytic cleavage that releases MMAE are what cause Adcertris’ anticancer effect.

The malignant cells’ cell cycle is arrested and they undergo apoptosis as a result of the binding of MMAE to tubulin, which disturbs the microtubule network inside the cell Label.

Uses it is used for the therapy of Classic Hodgkin lymphoma, Cutaneous anaplastic large cell lymphoma, Anaplastic large cell lymphoma, Mycosis fungoides, and Peripheral T-cell lymphoma which contains the CD30 protein
Contraindications The combined use of bleomycin and brentuximab is contraindicated because of pulmonary toxicity.
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Nivolumab (Opdivo) is another monoclonal antibody that got FDA approval for the treatment of classical Hodgkin’s Lymphoma in patients who have relapsed or progressed after autologous stem cell transplantation or posttransplantation brentuximab therapy.

Generic name: Nivolumab
Trade name: Opdivo, Opdualag
Company name: Bristol Myers Squibb
Date of approval: March 4, 2016 [ref]
MOA T-cell function is inhibited when the ligands PD-L1 and PD-L2 bind to the PD-1 receptor on these cells.

PD-L1 and PD-L2 are expressed by tumor cells.  Nivolumab binds to PD-1 and stops PD-L1 and PD-L2 from blocking T-cell activity, restoring a patient’s tumor-specific T-cell response.

Uses It is used in the therapy of unresectable or metastatic melanoma, classical Hodgkin lymphoma, small-cell lung cancer, urothelial carcinoma, esophageal cancer, hepatocellular carcinoma, and others.
Contraindications None
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Pembrolizumab (Keytruda) was granted accelerated approval for the treatment of refractory Hodgkin’s Lymphoma in 2017.

It is indicated in the treatment of relapsed or refractory Classical Hodgkin’s Lymphoma who have not responded to three or more prior therapies.

keytruda may also be used to treat relapsed HL after hematopoietic stem cell transplantation.

Generic name: Pembrolizumab
Trade name: Keytruda
Company name: Merck
Date of approval: March 14, 2017 [ref]
MOA Pembrolizumab blocks the interaction of the known ligands PD-L1 and PD-L2.8 with the cell surface receptor programmed cell death protein 1 (PD-1) with great affinity.

In normal conditions, the TCR-mediated T-cell proliferation and cytokine production are inhibited by the binding of the ligands of PD-1 to the receptor.

Following immunological responses against a pathogen, self-tolerance, minimizing collateral damage, and maternal tolerance to fetal tissue all appear to be influenced by this inhibitory signal.

The blocking of this inhibitory mechanism by pembrolizumab’s binding to PD-1 results in a physiological shift towards immunological reactivity, boosting tumor immunosurveillance and anti-tumor immune response.

Uses For the therapy of pediatric patients with refractory Classical Hodgkin Lymphoma, or one that has relapsed after two lines of therapy, or adult patients with relapsed or refractory Classical Hodgkin Lymphoma.
Contraindications None
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Prednisone (Deltasone) is a corticosteroid. It has strong anti-inflammatory properties. Corticosteroids are commonly used in various chemotherapeutic regimens because they reduce the inflammation associated with cell death.

Prednisone is used in the following regimens of Hodgkin’s Lymphoma:

  • MOPP:
    • Mechlorethamine,
    • Vincristine (Oncovin),
    • Procarbazine,
    • Prednisone
  • Stanford V:
    • Doxorubicin,
    • Vinblastine,
    • Mustard,
    • Bleomycin,
    • Vincristine,
    • Etoposide,
    • Prednisone
  • BEACOPP:
    • Bleomycin,
    • Etoposide,
    • Doxorubicin,
    • Cyclophosphamide,
    • Vincristine,
    • Procarbazine,
    • Prednisone
  • DHAP:
    • Cisplatin,
    • Cytarabine,
    • Prednisone
Generic name: Prednisone
Trade name: Deltasone, Rayos, Winpred
Company name: Geneyork Pharmaceutical
Date of approval: July 26, 2012 [ref]
MOA Prednisolone, a glucocorticoid agonist corticosteroid, is the active form of prednisone after being first metabolized in the liver.

Corticosteroids’ immediate side effects include reduced capillary permeability, vasodilation, and leukocyte migration to inflammatory areas.

Changes in gene expression caused by corticosteroids’ binding to the glucocorticoid receptor have a variety of long-lasting consequences that might last for hours or even days.

In addition to inhibiting phospholipase A2, which reduces the production of arachidonic acid derivatives, glucocorticoids also boost anti-inflammatory genes like interleukin-10 and inhibit NF-Kappa B and other inflammatory transcription factors.

While greater dosages of corticosteroids inhibit the immune system, lower amounts have an anti-inflammatory effect.

Long-term administration of high dosages of glucocorticoids binds to the mineralocorticoid receptor, increasing sodium levels and lowering potassium levels.

Uses In order to reduce inflammation in the body for Hodgkin lymphoma prednisone is the most frequently used corticosteroid.
Contraindications
  • Documented hypersensitivity
  • Administration of live or attenuated live vaccine
  • Untreated serious infections
  • Varicella
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