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

It is important to note that ANC should be more than 500 cells/mm³ and platelets more than 50,000 cells/mm³ before initiating new cycles of therapy.

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

• Oral: it is given as 4 mg once a day on days 1 to 21 of 28-day cycles in combination with dexamethasone.
• It is continued until disease progression or unacceptable toxicity has occurred.
• Off-label combinations:
  • Oral:
    • It is given as 4 mg once a day on days 1 to 21 of 28-day cycles in combination with elotuzumab and dexamethasone until disease progression or unacceptable toxicity have occurred OR
    • 4 mg once daily on days 1 to 21 of 28-day cycles that too in combination with daratumumab and dexamethasone until disease progression has stopped.
• Dosage adjustment for concomitant therapy with strong CYP1A2 inhibitors:
  • Avoid concurrent use of strong CYP1A2 inhibitors. If concomitant use of strong CYP1A2 inhibitors cannot be avoided, reduce the pomalidomide dose by half of recommended dose.

Use in Children:

Not indicated.   

Pomalidomide (Pomalyst) Pregnancy Category: X

• [US Boxed Warning]Pregnancy is not a good time to take pomalidomide.
• Pomalidomide can be used as an analog to thalidomide.
• Thalidomide, a human teratogen known to cause severe birth defects and miscarriages, is known.
• Amelia, phocomelia and bone defects were all observed in humans after thalidomide exposure. Infant mortality can reach 40% within a few hours of birth.
• If a pregnancy occurs during pomalidomide treatment, immediately withhold.
• [US Boxed Warning]Before starting pomalidomide treatment for females with reproductive potential, you should have two negative pregnancy tests.
• You should use two forms of contraceptive method during therapy, and continue them for 4 weeks after you stop.
• Only women with childbearing potential should receive treatment if they can comply with the Pomalyst REMS Program conditions.
• After 4 weeks, the patient must stop trying to conceive.
• Females with reproductive potential should use contraception during treatment, interruptions to treatment and for 4 weeks after the discontinuation of pomalidomide.
• A woman with reproductive potential must use two forms of reliable contraception, or total abstinence of heterosexual intercourse, even if she has a history of infertility.
• One method of birth control that is reliable includes tubal ligation (eg., IUD, hormone [birth control pills or injections, patches, vaginal rings or implants], partner's vasectomy, or tubal ligation) and one other method (eg., male latex, synthetic condom, diaphragm or cervical cap).
• Before beginning therapy, pregnancy tests should be performed 10-14 days and 24 hours before starting treatment. 
• For the first 4 weeks, then weekly and every 4 weeks thereafter (every 2 week if your menstrual cycle is irregular). Therapy interruptions are for at most 4 weeks.
• Pomalidomide should be immediately stopped if there is a missed period or abnormal pregnancy test. 
• If pregnancy is suspected during treatment, the patient should be referred immediately to a specialist in reproductive toxicology.
• The semen of males who take this medication contains pomalidomide.
• The vasectomized males should use a latex condom or synthetic condom for any sexual contact with females of childbearing years during treatment, interruptions and 4 weeks after discontinuation.
• Patients undergoing therapy should avoid sperm donation.
• Any suspicion of fetal exposure should go to the FDA via MedWatch (1-800-3321088) or to Celgene Corporation (1-1-888-423-5436).

Use of pomalidomide while breastfeeding

• It is unknown if breast milk contains it.
• It can cause serious side effects and should not be used during breastfeeding. If therapy is to continue, the clinician must assess whether the benefits outweigh any risks.

Pomalidomide (Pomalyst) Dose in Kidney Disease:

• CrCl ≥15 to <60 mL/minute:
  • There are no dosage adjustments provided in the literature. When compared to patients with normal renal function, pomalidomide pharmacokinetics were not significantly altered in patients with CrCl between 15 to 60 mL/minute.
• Hemodialysis:
  • Initially, it is given as  3 mg once a day. it should be administered after hemodialysis on dialysis days. Hemodialysis can remove pomalidomide from circulation.
• CrCl <45 mL/minute, including hemodialysis (off-label):
  • Results from a phase II study of pomalidomide in combination with low-dose dexamethasone for treatment of relapsed or refractory multiple myeloma suggest that pomalidomide 4 mg once daily (for 21 days of a 28-day treatment cycle) was safe and effective in patients with CrCl <45 mL/minute, including patients requiring hemodialysis.
• The International Myeloma Working Group (IMWG) recommendations:
  • The IMWG recommends use of the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation (preferred) or the Modification of Diet in Renal Disease (MDRD) formula to evaluate renal function estimation in multiple myeloma patients with a stable serum creatinine.
• CrCl ≥45 mL/minute:
  • No dose adjustments are needed.

Pomalidomide (Pomalyst) Dose in Liver disease:

• Hepatic impairment prior to treatment:
  • Mild or moderate impairment (Child-Pugh class A or B):
    • Initially, it is given as 3 mg once a day.
  • Severe impairment (Child-Pugh class C):
    • Initially, it is given as 2 mg once a day
• Hepatic impairment during treatment:
  • If liver enzymes are elevated, stop pomalidomide, and evaluate. When liver enzymes return to baseline, one might consider restarting pomalidomide at a lower dose.

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):

• Pregnancy
• Canadian labeling: Additional contraindications not in the US labeling
• Hypersensitivity to thalidomide or lenalidomide or any other component of the formulation is an absolute contraindication.
  • Breastfeeding
  • Two effective methods of contraception are not available to women with childbearing potential.
  • Male patients are unable to adhere to contraceptive measures.

Warnings and precautions

• Suppression of bone marrow
  • In clinical trials, anemia, neutropenia, and thrombocytopenia were all frequently reported. The most common grade 3/4 adverse events were anemia and neutropenia.
  • Neutropenic fever was also seen.
  • For the first 8 weeks, monitor complete blood counts weekly.
  • Then, every other week or as indicated by the doctor thereafter, you will need to check them monthly. 
  • Depending on the patient's counts, therapy may need to be interrupted, reduced or discontinued.
• CNS effects
  • It can cause confusion or dizziness. It is important to exercise caution when operating machinery or driving.
  • Avoid taking concurrent medications, as they can cause confusion and dizziness.
• Hepatotoxicity
  • There have been reports of fatalities due to hepatic dysfunction. Elevated bilirubin levels and elevated ALT were also reported.
  • Perform liver function tests regularly.
  • Consider stopping treatment for high liver enzymes, and reducing doses after enzymes return back to baseline.
• Hypersensitivity reactions
  • Reports of angioedema, severe cutaneous reactions such as Stevens-Johnson Syndrome [SJS], toxic epidermal Necrolysis [TEN], and drug reactions with eosinophilia or systemic symptoms [DRESS] were all reported.
  • DRESS can manifest as a cutaneous reaction, such as a rash, exfoliative, or dermatitis.
  • It may also cause eosinophilia and fever. There may also be lymphadenopathy with systemic problems, which could include hepatitis and myocarditis.
  • Stop treating angioedema, skin peeling, bullae, or any other severe cutaneous reactions such as SJS, TEN and DRESS. Do not resume therapy in such situations.
• Interstitial lung disease (ILD).
  • There have been reports of ILD and other related events, such as pneumonitis.
• Neuropathy
  • Clinical trials showed peripheral and sensory neuropathy in some cases, but no cases of grade 4-related neuropathy.
  • Pay attention to any signs and symptoms of neuropathy. This may lead to therapy interruption, dose adjustment, or discontinuation.
• Secondary malignancy
  • Patients who received pomalidomide for the investigation of multiple myeloma have been diagnosed with acute myelogenous lymphoma (AML).
• [US Boxed Warning]: Thromboembolic Events
  • Multiple myeloma patients have experienced venous and arterial events, including pulmonary embolism (PE), deep vein thrombosis, stroke, and pulmonary embolism (DVT) during pomalidomide therapy.
  • Antithrombotic prophylaxis was used in clinical trials.
  • Thromboprophylaxis should be considered and should be based upon the patient's underlying risks.
  • Cerebrovascular ischemia, ischemic heart disease and cerebrovascular thrombotic events are also examples of arterial thrombotic activities.
  • If you notice signs and symptoms of thromboembolism, such as shortness of breath, chest pain or arm or leg swelling, be sure to alert your doctor immediately.
• Tumor lysis syndrome
  • Patients with high tumor burdens should be closely monitored for signs of tumor lysis syndrome.
  • It is important to manage hyperuricemia actively
• Hepatic impairment
  • It is important to be cautious as it is metabolized by the liver. In such cases, the risk of systemic exposure increases.
  • Patients with hepatic impairment should be adjusted the first dose.
• Multiple myeloma
  • Two clinical studies showed an increase in mortality in patients with multiple myeloma treated with pembrolizumab and thalidomide analogs, as well as dexamethasone.
  • The experimental arm, which contained pembrolizumab and dexamethasone and a thalidomide analogue [pomalidomide and lenalidomide], was responsible for myocarditis and Stevens-Johnson Syndrome, MI, pericardial bleeding, cardiac failure, respiratory infection, neutropenic seizures, sepsis with multiple organ dysfunction, respiratory failure and intestinal ischemia. It also included suicide, cardiac arrest, pulmonary embolism and cardiac arrest.
  • Multiple myeloma has not been approved for PD-1 and PD-L1 blocking antibody treatment.
  • Pembrolizumab should never be used in conjunction with thalidomide analogs or dexamethasone to treat multiple myeloma unless it is part of a clinical trial.
• Renal impairment
  • Manufacturers recommend making initial dose adjustments.

Pomalidomide: Drug Interaction

Monitoring parameters:

• CBC with differential and platelets weekly during the first 8 weeks, and then monthly or as required by clinical necessity thereafter.
• Renal function, i.e. serum creatinine and creatinine clearance
• Monthly liver function tests.
• Monitor patients at high risk for thromboembolism, neuropathy and tumor lysis syndrome.
• Thyroid function tests (TSH) are recommended at baseline, and every 2 to 3-months during treatment for structurally related medications.
• Monitor compliance.

Females with childbearing potential

• Pregnancy test 10-14 days and 24 hours before initiating therapy. This is for women who have regular periods, or women who have irregular periods.
• After discontinuing pregnancy tests, you should continue to have your pregnancies tested for at least four weeks.

How to administer Pomalidomide (Pomalyst)?

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

Missed doses:

• One can administer a missed dose if within 12 hours of the usual dosing time.
• If more than 12 hours have elapsed, then skip the dose for that day and resume the usual dosing the following day.
• Do not take 2 doses to make up for a skipped dose.

Mechanism of action of Pomalidomide (Pomalyst):

• Pomalidomide causes cell cycle arrest and apoptosis in multiple myeloma cells. 
• It increases T cell- and natural killer cell-mediated cytotoxicity, inhibits proinflammatory cytokines tumor nefara (TNFa), IL-1 and IL-6 and inhibits angiogenesis.

Absorption:

• Rapid;
• slowed by food.

Distribution: Semen distribution is ~67% of plasma levels

Protein binding:

• 12% to 44%

Metabolism:

• Hepatic via CYP1A2 and CYP3A4.
• Via CYP2C19 and CYP2D6 (minor)

Half-life elimination:

• About 9.5 hours (healthy subjects).
• About7.5 hours (multiple myeloma patients)

Time to peak:

• 2 to 3 hours

Excretion:

• Urine (73%; 2% as unchanged drug).
• Via feces (15%; 8% as unchanged drug)

International Brand Names of Pomalidomide:

• Pomalyst
• Imnovid

Pomalidomide Brand Names in Pakistan:

No Brands Available in Pakistan.