Mylomid

Approved Indications:

• Multiple Myeloma (MM):
• In combination with dexamethasone for adults with newly diagnosed multiple myeloma.
• As maintenance therapy following autologous stem cell transplant (ASCT).
• Myelodysplastic Syndromes (MDS):
• For transfusion-dependent anemia due to low- or intermediate-1-risk MDS associated with a deletion 5q cytogenetic abnormality, with or without additional cytogenetic abnormalities.
• Mantle Cell Lymphoma (MCL):
• For adult patients whose disease has relapsed or progressed after at least two prior therapies, including bortezomib.

Important Off-Label (Clinically Accepted) Uses:

• Follicular Lymphoma and Marginal Zone Lymphoma (in combination with rituximab):
• Used in relapsed or refractory cases under hematology-oncology supervision.
• Cutaneous T-cell Lymphoma (CTCL):
• In selected relapsed/refractory patients based on clinical experience.

General Administration:

• Administer orally, once daily, with or without food.
• Capsules should be swallowed whole with water. Do not open, crush, or chew.

Adults:

• Multiple Myeloma (with dexamethasone):
• Lenalidomide: 25 mg orally once daily on Days 1–21 of a 28-day cycle.
• Dexamethasone: 40 mg orally on Days 1, 8, 15, and 22.
• Continue until disease progression or unacceptable toxicity.
• Maintenance Therapy (post-ASCT):
• Start with 10 mg orally once daily on Days 1–28 of repeated 28-day cycles.
• Dose may be increased to 15 mg daily if tolerated.
• Myelodysplastic Syndromes (with deletion 5q):
• 10 mg orally once daily continuously.
• Discontinue if no response after 4 months or upon disease progression.
• Mantle Cell Lymphoma:
• 25 mg orally once daily on Days 1–21 of a 28-day cycle.
• Continue until disease progression or toxicity.

Pediatric Use:

• Safety and efficacy have not been established.

Elderly:

• Use with caution. Adjust dose based on renal function.

Renal Impairment:

Hepatic Impairment:

• Use with caution; no specific adjustment recommendations due to minimal hepatic metabolism.

Lenalidomide is an immunomodulatory agent that acts by multiple mechanisms. It binds to cereblon, a substrate receptor of the CRL4 E3 ubiquitin ligase complex, leading to the ubiquitination and proteasomal degradation of key transcription factors, such as Ikaros and Aiolos. This results in direct anti-proliferative effects on malignant cells. Lenalidomide also enhances T-cell and natural killer (NK) cell function, inhibits pro-inflammatory cytokines like TNF-α and IL-6, and blocks angiogenesis by downregulating VEGF and other angiogenic factors. These combined effects contribute to its antitumor activity.

• Absorption: Rapidly absorbed; peak plasma concentrations reached within 0.6 to 1.5 hours after oral administration.
• Bioavailability: Approximately 90%.
• Distribution: Volume of distribution ~75 L; plasma protein binding ~30%.
• Metabolism: Minimal hepatic metabolism.
• Elimination: Excreted primarily unchanged via the kidneys (~80%).
• Half-life: Approximately 3 to 5 hours in patients with normal renal function.
• Onset of Action: Varies by indication; clinical response may take multiple treatment cycles.

• Pregnancy: Contraindicated. Lenalidomide is a known human teratogen and is associated with severe birth defects and fetal death. Females of reproductive potential must adhere to strict contraception and regular pregnancy testing. Part of a controlled distribution program (e.g., REMS).
• Lactation: Unknown if excreted in human breast milk. Due to the risk of serious adverse effects in nursing infants, breastfeeding is not recommended during treatment.

• Primary Class: Immunomodulatory Agent (IMiD)

Subclass: Thalidomide Derivative

• Known hypersensitivity to lenalidomide or any component of the formulation
• Pregnancy (due to high teratogenic risk)
• Uncontrolled hypersensitivity reactions to thalidomide analogs

• Teratogenicity: Lenalidomide is highly teratogenic. Enroll in a pregnancy prevention program. Contraindicated in pregnancy.
• Hematologic Toxicity: May cause severe neutropenia and thrombocytopenia. Monitor CBCs weekly for the first 8 weeks and monthly thereafter.
• Venous and Arterial Thromboembolism: Risk increases when used with dexamethasone. Thromboprophylaxis is recommended.
• Hepatotoxicity: Monitor liver function tests regularly. Cases of hepatic failure have occurred.
• Second Primary Malignancies: Increased risk in patients with multiple myeloma. Monitor for signs of secondary cancer.
• Severe Cutaneous Reactions: Risk of Stevens-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN). Discontinue if rash is severe.
• Tumor Lysis Syndrome: Monitor high-risk patients closely.

Common Adverse Effects:

• Hematologic: Neutropenia, anemia, thrombocytopenia
• Gastrointestinal: Diarrhea, constipation, nausea, vomiting
• General: Fatigue, asthenia, pyrexia
• Musculoskeletal: Muscle cramps, arthralgia, back pain
• Neurologic: Dizziness, headache
• Infections: Upper respiratory tract infections, pneumonia

Serious/Rare Side Effects:

• Deep vein thrombosis (DVT), pulmonary embolism
• Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN)
• Hepatic failure, elevated liver enzymes
• Second primary malignancies (e.g., AML, solid tumors)
• Tumor lysis syndrome
• Hypersensitivity reactions (including angioedema)

• P-glycoprotein Substrates (e.g., digoxin): Lenalidomide may increase serum levels of digoxin; monitor closely.
• Anticoagulants and Antiplatelet Agents: Increased risk of bleeding. Use with caution.
• Concomitant Dexamethasone: Enhances risk of thromboembolic events; thromboprophylaxis advised.
• Cytochrome P450 System: Lenalidomide is not a significant CYP450 substrate, inducer, or inhibitor, reducing interaction risk.

• FDA Update: Lenalidomide approved for maintenance therapy following ASCT in multiple myeloma.
• NCCN Guidelines: Support the use of lenalidomide-based regimens in relapsed/refractory non-Hodgkin lymphomas, including the R² regimen (lenalidomide + rituximab).
• REMS Program: Updated requirements for pregnancy prevention and risk mitigation.

• Storage Temperature: 20°C to 25°C (68°F to 77°F); excursions permitted between 15°C and 30°C.
• Humidity/Light Protection: Store in original container. Protect from moisture and light.
• Handling Precautions: Handle with care. Do not open or crush capsules. Use gloves if contact with capsule contents is likely.
• Disposal: Dispose of according to local hazardous waste regulations due to teratogenic potential.