Pomalidomide is a medication that belongs to a class of drugs known as immunomodulatory agents. It is primarily used in the treatment of certain types of cancer, specifically multiple myeloma. Pomalidomide works by affecting the immune system and inhibiting the growth of cancer cells. It is taken orally in the form of capsules, usually once daily, and is often used in combination with other medications.

Pomalidomide (Pomalyst) is a derivative of thalidomide. It has got cytotoxic, immune-modulator, and anti-angiogenic properties. It is used in combination with dexamethasone to treat patients with multiple myeloma.

Pomalidomide (Pomalyst) Uses:

• Relapsed/ refractory Multiple Myeloma:
  • It is used in treatment of multiple myeloma along with dexamethasone in patients who have received at least 2 prior therapies, including lenalidomide and a proteasome inhibitor, and have demonstrated disease progression after or within 60 days of completion of the prior therapy.

Pomalidomide (Pomalyst) Dose in Adults

Note: Before starting new cycles of therapy with pomalidomide, it is important to make sure that certain blood cell counts are within a specific range. The ANC (absolute neutrophil count) should be equal to or greater than 500 cells per millimeter (mm), and the platelet count should be equal to or greater than 50,000 cells per mm. These counts help ensure that the body has enough healthy white blood cells and platelets to fight infections and prevent bleeding.

Pomalidomide (Pomalyst) Dose in the treatment of relapsed/ refractory multiple myeloma:

• The recommended dose of pomalidomide for the treatment of relapsed/refractory multiple myeloma is 4 mg taken orally once daily.
• This dosage is typically followed for 21 days out of a 28-day cycle.
• It is commonly used in combination with dexamethasone, a steroid medication.
• This treatment regimen should be continued until there is disease progression or the patient experiences unacceptable side effects.

Off-label combinations:

• Pomalidomide may be used off-label in combination with other medications.
• For example, when combined with elotuzumab and dexamethasone or daratumumab and dexamethasone, the recommended dose and schedule remain the same.

Dosage adjustment for concomitant therapy with strong CYP1A2 inhibitors:

• If a patient is also taking strong CYP1A2 inhibitors, it is generally advised to avoid using them concurrently with pomalidomide.
• However, if avoiding concomitant use is not possible, the pomalidomide dose should be reduced by 50% to mitigate potential interactions or adverse effects.

Use in Children:

Not indicated.   

Pomalidomide (Pomalyst) Pregnancy Category: X

• Pomalidomide should never be used during pregnancy as it can cause severe birth defects or death to the developing baby.
• It is similar to a medication called thalidomide, which is known to be harmful to human babies.
• Some of the birth defects caused by thalidomide include missing limbs, bone problems, eye and ear abnormalities, facial paralysis, heart defects, and problems with the urinary and genital organs.
• If a pregnancy occurs while taking pomalidomide, the treatment should be stopped immediately.
• Women who can become pregnant should have two negative pregnancy tests before starting pomalidomide and use two forms of birth control or completely avoid sexual activity for at least four weeks after stopping the medication.
• Regular pregnancy tests should be done during treatment and for four weeks after stopping pomalidomide.
• Men taking pomalidomide should also use condoms during sexual contact with women who can become pregnant, and they should not donate sperm.
• If there is any suspicion of pregnancy or exposure to the drug, it should be reported to the FDA and the prescribing company.

Use of pomalidomide while breastfeeding

• The presence of pomalidomide in breast milk is unknown, and it is advised not to use it while breastfeeding.
• The medication can potentially cause significant side effects, so its use during breastfeeding should be avoided.
• If there is a need to continue therapy with pomalidomide, the healthcare provider should carefully evaluate whether the benefits of treatment outweigh any potential risks to the nursing infant.

Pomalidomide (Pomalyst) Dose in Kidney Disease:

• For patients with a creatinine clearance (CrCl) level of 15 to less than 60 mL/minute, there is no specific dosage adjustment mentioned in the manufacturer's labeling for pomalidomide. Studies have shown that the pharmacokinetics of pomalidomide were not significantly affected in patients with CrCl between 15 and 60 mL/minute compared to those with normal kidney function.

• In the case of patients undergoing hemodialysis, an initial dose of 3 mg of pomalidomide is recommended once daily. It should be administered after the hemodialysis procedure on dialysis days since hemodialysis can remove pomalidomide from the bloodstream.

• In some off-label cases where the CrCl is less than 45 mL/minute, including patients requiring hemodialysis, a phase II study suggested that a dose of 4 mg of pomalidomide once daily for 21 days out of a 28-day treatment cycle was safe and effective when used in combination with low-dose dexamethasone for the treatment of relapsed/refractory multiple myeloma.

• To assess renal function in multiple myeloma patients with a stable serum creatinine, the International Myeloma Working Group (IMWG) recommends using either the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (preferred) or the Modification of Diet in Renal Disease (MDRD) formula.

• For patients with a CrCl of 45 mL/minute or higher, no dosage adjustment is required for pomalidomide.

Pomalidomide (Pomalyst) Dose in Liver disease:

Before starting treatment with pomalidomide, the dosage may need to be adjusted based on the severity of hepatic impairment.

• For patients with mild or moderate impairment (Child-Pugh class A or B), the initial dose is typically 3 mg once daily.
• For patients with severe impairment (Child-Pugh class C), the initial dose is usually reduced to 2 mg once daily.

• During the course of treatment, if liver enzymes become elevated, it is recommended to discontinue pomalidomide and evaluate the liver function.
• Once the liver enzymes return to baseline levels, the healthcare provider may consider restarting the medication at a lower dose to minimize the risk of liver-related side effects.
• It's important to closely monitor liver function throughout treatment with pomalidomide and promptly report any signs of liver problems, such as jaundice (yellowing of the skin or eyes), dark urine, or abdominal pain.
• Individualized dosage adjustments and careful monitoring are necessary for patients with hepatic impairment to ensure the medication is safely and effectively administered.

Common Side Effects of Pomalidomide (Pomalyst):

• Cardiovascular:
  • Peripheral Edema
• Central Nervous System:
  • Fatigue
  • Dizziness
  • Peripheral Neuropathy
  • Neuropathy
  • Headache
  • Anxiety
  • Confusion
• Dermatologic:
  • Skin Rash
  • Pruritus
• Endocrine & Metabolic:
  • Hypercalcemia
  • Weight Loss
  • Hypokalemia
  • Hyperglycemia
  • Hyponatremia
• Gastrointestinal:
  • Constipation
  • Nausea
  • Diarrhea
  • Decreased Appetite
  • Vomiting
• Hematologic & Oncologic:
  • Neutropenia
  • Anemia
  • Thrombocytopenia
  • Leukopenia
• Neuromuscular & Skeletal:
  • Weakness
  • Back Pain
  • Musculoskeletal Chest Pain
  • Muscle Spasm
  • Arthralgia
  • Myasthenia
  • Musculoskeletal Pain
  • Ostealgia
• Renal:
  • Increased Serum Creatinine
  • Renal Failure
• Respiratory:
  • Upper Respiratory Tract Infection
  • Dyspnea
  • Pneumonia
  • Cough
  • Epistaxis
• Miscellaneous:
  • Fever

Less Common Side Effects Of Pomalidomide (Pomalyst):

• Central Nervous System:
  • Chills
  • Insomnia
• Dermatologic:
  • Xeroderma
  • Hyperhidrosis
• Endocrine & Metabolic:
  • Dehydration
  • Hypocalcemia
• Genitourinary:
  • Urinary Tract Infection
• Hematologic & Oncologic:
  • Febrile Neutropenia
  • Lymphocytopenia
• Infection:
  • Sepsis
• Neuromuscular & Skeletal:
  • Tremor
  • Limb Pain
• Respiratory:
  • Productive Cough
  • Oropharyngeal Pain
• Miscellaneous:
  • Night Sweats

Frequency of Side effects Not Defined:

• Cardiovascular:
  • Angina Pectoris
  • Atrial Fibrillation
  • Congestive Cardiac Failure
  • Hypotension
  • Myocardial Infarction
  • Septic Shock
  • Syncope
• Central Nervous System:
  • Altered Mental Status
  • Falling
  • Impaired Consciousness
  • Noncardiac Chest Pain
  • Vertigo
• Dermatologic:
  • Cellulitis
• Endocrine & Metabolic:
  • Hyperkalemia
• Gastrointestinal:
  • Abdominal Pain
  • Clostridioides Difficile
• Genitourinary:
  • Pelvic Pain
  • Urinary Retention
  • Urosepsis
• Hepatic:
  • Hyperbilirubinemia
  • Increased Serum ALT
• Infection:
  • Bacteremia
  • Neutropenic Sepsis
  • Viral Infection
• Neuromuscular & Skeletal:
  • Bone Fracture
  • Vertebral Compression Fracture
• Respiratory:
  • Bronchospasm
  • Interstitial Pulmonary Disease
  • Lobar Pneumonia
  • Pneumonia Due To Pneumocystis Carinii
  • Respiratory Syncytial Virus Infection
• Miscellaneous:
  • Failure To Thrive
  • Multiorgan Failure
  • Physical Health Deterioration

Contraindications to Pomalidomide (Pomalyst):

• In addition to the contraindications mentioned in the US labeling, the Canadian labeling for pomalidomide includes some additional contraindications.
• These contraindications state that pomalidomide should not be used in individuals who have hypersensitivity or allergic reactions to pomalidomide, thalidomide, lenalidomide, or any of the components of the medication's formulation.
• Pomalidomide is also contraindicated in breastfeeding individuals.
• Furthermore, women of childbearing potential who are not using two effective methods of contraception and male patients who are unable to comply with the required contraceptive measures should not use pomalidomide.
• These contraindications aim to prevent potential harm to the patient and the developing baby during pregnancy and breastfeeding and to ensure proper contraceptive practices are followed to avoid unintended pregnancies.

Warnings and precautions

Suppression of bone marrow

• During clinical trials, it was often observed that pomalidomide can cause bone marrow suppression, which includes low levels of neutrophils (a type of white blood cell), red blood cells (anemia), and platelets (thrombocytopenia).
• Among these, neutropenia was the most commonly reported severe adverse event, followed by anemia and thrombocytopenia.
• Neutropenic fever has also been reported.
• To monitor for these effects, complete blood counts should be checked weekly for the first 8 weeks of treatment and then monthly or as advised by the healthcare professional.
• Depending on the severity, it may be necessary to interrupt, reduce the dose, or discontinue pomalidomide therapy.

CNS effects

• Pomalidomide may have effects on the central nervous system (CNS) such as dizziness and confusion.
• Patients should be cautious and avoid engaging in activities that require mental alertness, like operating machinery or driving, while taking this medication.
• It is important to also avoid taking other medications that may worsen dizziness and confusion as a result of their interactions with pomalidomide.

Hepatotoxicity

• Pomalidomide has been associated with hepatotoxicity, including cases of liver failure that have resulted in fatalities.
• Elevated levels of bilirubin (a marker of liver function) and ALT (a liver enzyme) have also been observed.
• It is important to monitor liver function tests regularly while taking this medication.
• If liver enzymes become elevated, treatment with pomalidomide should be temporarily interrupted.
• Once the liver enzymes return to baseline levels, the healthcare provider may consider reducing the dose of the medication.
• Prompt monitoring and appropriate management of liver function are crucial to minimize the risk of hepatotoxicity and ensure the safety of the patient.

Hypersensitivity reactions

• Hypersensitivity reactions have been reported with the use of pomalidomide.
• These reactions can include angioedema (swelling), as well as severe cutaneous reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS).
• DRESS can present with symptoms such as rash, exfoliative dermatitis (skin peeling), eosinophilia (elevated levels of a type of white blood cell), fever, and/or swollen lymph nodes.
• It may also involve systemic complications affecting the liver, kidneys, lungs, heart, or lining around the heart.
• If angioedema, severe skin reactions, or other serious cutaneous reactions occur, treatment with pomalidomide should be immediately stopped, and reinitiating the therapy should be avoided.
• Prompt medical attention and appropriate management are necessary to ensure the patient's safety and well-being.

Interstitial lung disease (ILD).

• Cases of interstitial lung disease (ILD) and related events, such as pneumonitis, have been reported in individuals taking pomalidomide.
• ILD is a condition that involves inflammation and scarring of the lung tissue, which can lead to breathing difficulties and other respiratory symptoms.
• It is important for patients taking pomalidomide to be aware of the potential risk of ILD and to promptly report any new or worsening respiratory symptoms to their healthcare provider.
• Early detection and appropriate management are crucial in order to minimize the impact of ILD and related complications.

Neuropathy

• During clinical trials, peripheral and sensory neuropathy, including some cases of grade 3 severity, were reported in patients receiving pomalidomide.
• However, no cases of grade 4 neuropathy were observed.
• It is important to closely monitor for any signs or symptoms of neuropathy while taking pomalidomide.
• This may include numbness, tingling, pain, or weakness in the hands or feet.
• If neuropathy develops or worsens, the healthcare provider may consider interrupting the therapy, modifying the dosage, or discontinuing pomalidomide as necessary.

Secondary malignancy

• In some cases, the development of acute myelogenous leukemia (AML) as a secondary malignancy has been reported in patients who received pomalidomide as part of investigational treatment for conditions other than multiple myeloma.
• AML is a type of cancer that affects the bone marrow and blood cells.
• While the occurrence of AML as a secondary malignancy is rare, it is important to be aware of this potential risk.
• Patients should discuss any concerns or symptoms with their healthcare provider, who can provide guidance on monitoring and managing the risks associated with pomalidomide treatment.

[US Boxed Warning]: Thromboembolic Events

• It is important to be aware of the risk of thromboembolic events, as indicated by a boxed warning in the United States.
• Patients with multiple myeloma who receive pomalidomide therapy may experience venous and arterial thromboembolic events, such as deep vein thrombosis (DVT), pulmonary embolism (PE), heart attack (MI), and stroke.
• Clinical trials have used preventive measures against blood clots.
• It is recommended to assess the patient's individual risk factors and provide appropriate thromboprophylaxis.
• Arterial thrombotic events can also include conditions like cerebrovascular ischemia (reduced blood flow to the brain) and ischemic heart disease (reduced blood flow to the heart).
• It is important to monitor for signs and symptoms of blood clots, such as shortness of breath, chest pain, or swelling in the arms or legs, and advise patients to seek immediate medical attention if these symptoms occur.

Tumor lysis syndrome

• Patients with a high tumor burden who are receiving pomalidomide treatment may be at risk for a condition called tumor lysis syndrome.
• Tumor lysis syndrome can occur when cancer cells are rapidly destroyed, releasing their contents into the bloodstream.
• This can lead to electrolyte imbalances and an increase in uric acid levels, resulting in potential complications.
• It is important to closely monitor patients at risk and take appropriate measures to manage hyperuricemia (high levels of uric acid in the blood).
• This may involve medications or other interventions to prevent or treat elevated uric acid levels.

Hepatic impairment

• Caution should be exercised when using pomalidomide in patients with hepatic impairment.
• Pomalidomide is processed by the liver, and individuals with liver dysfunction may experience increased levels of the drug in their system.
• Therefore, it is recommended to make an initial dosage adjustment for patients with hepatic impairment.

Multiple myeloma

• In clinical studies, the use of pembrolizumab (a PD-1 or PD-L1 blocking antibody) in combination with a thalidomide analogue and dexamethasone in patients with multiple myeloma was associated with an increased risk of death.
• The causes of death observed in the group receiving the experimental treatment included various serious conditions such as myocarditis, Stevens-Johnson syndrome, heart attack, pericardial hemorrhage, cardiac failure, respiratory tract infection, and others.
• It is important to note that using pembrolizumab to treat multiple myeloma in combination with a thalidomide analogue and dexamethasone is not an approved treatment and should only be considered as part of a clinical trial.
• The findings highlight the need for caution and careful evaluation of treatment options in multiple myeloma patients.

Renal impairment

• Patients with renal impairment, particularly those undergoing hemodialysis, may require an initial dosage adjustment when using pomalidomide.
• The manufacturer recommends considering a modified dosage regimen for these individuals.
• Since hemodialysis can remove pomalidomide from the circulation, it is important to administer the medication after the dialysis procedure on dialysis days.

Pomalidomide: Drug Interaction

Monitoring parameters:

• CBC with differential and platelets:
  • Weekly for the first 8 weeks
  • Monthly or as clinically necessary thereafter
• Renal function:
  • Measure serum creatinine and creatinine clearance
• Liver function tests:
  • Monthly monitoring
• Signs/symptoms to monitor:
  • Thromboembolism (shortness of breath, chest pain, arm or leg swelling)
  • Neuropathy (peripheral and sensory symptoms)
  • Tumor lysis syndrome (in patients at risk)
  • Hypersensitivity/dermatologic reactions
  • Interstitial lung disease
• Consider thyroid function tests:
  • TSH recommended at baseline
  • Repeat every 2 to 3 months during treatment (based on similar medications)
• Adherence monitoring:
  • Regularly assess patient adherence to the treatment regimen

For Women of Childbearing Potential:

• Pregnancy testing:
  • 10 to 14 days and 24 hours before starting therapy
  • Weekly during the first month
  • Monthly thereafter for women with regular menstrual cycles
  • Every 2 weeks for women with irregular menstrual cycles
• Continue pregnancy testing for at least 4 weeks after discontinuation of pomalidomide treatment.

How to administer Pomalidomide (Pomalyst)?

• Administer the medication without regard to meals.
• Take the capsules whole with water. Do not break, chew, or open the capsules.

Missed Doses:

• If you miss a dose but it is within 12 hours of your usual dosing time, you may still take the missed dose.
• If it has been more than 12 hours since your usual dosing time, skip the missed dose for that day. Resume your regular dosing schedule the following day.
• Do not take two doses to make up for a missed dose.

Mechanism of action of Pomalidomide (Pomalyst):

• Cell cycle arrest and apoptosis: Pomalidomide directly induces cell cycle arrest and promotes apoptosis in multiple myeloma cells.
• Enhanced cytotoxicity: It enhances the cytotoxicity mediated by T cells and natural killer (NK) cells, leading to the destruction of cancer cells.
• Inhibition of proinflammatory cytokines: Pomalidomide inhibits the production of proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), and interleukin-12 (IL-12), which are involved in the inflammatory response.
• Angiogenesis inhibition: It also inhibits angiogenesis, the formation of new blood vessels, which is crucial for tumor growth and spread.

These mechanisms contribute to the therapeutic effects of pomalidomide in the treatment of multiple myeloma.

Absorption:

• Pomalidomide is rapidly absorbed, but its absorption is slowed down by food.

Distribution:

• It has a large volume of distribution (V) ranging from 62 to 138 liters.
• The drug is also distributed in semen, with levels approximately 67% of plasma levels.

Protein binding:

• Pomalidomide is moderately bound to proteins in the blood, with binding ranging from 12% to 44%.

Metabolism:

• The drug is primarily metabolized in the liver by enzymes CYP1A2 and CYP3A4, with minor contributions from CYP2C19 and CYP2D6.

Elimination half-life:

• In healthy subjects, the elimination half-life of pomalidomide is approximately 9.5 hours, while in patients with multiple myeloma, it is around 7.5 hours.

Time to peak:

• Pomalidomide reaches its peak concentration in the blood around 2 to 3 hours after administration.

Excretion:

• The drug is mainly eliminated through the urine, with approximately 73% of the dose excreted in this way (including 2% as unchanged drug).
• About 15% of the dose is excreted in the feces (including 8% as unchanged drug).

International Brand Names of Pomalidomide:

• Pomalyst
• Imnovid

Pomalidomide Brand Names in Pakistan:

No Brands Available in Pakistan.