What are the potential side effects of Lenalidomide (immunomodulatory drug) in an adult patient, possibly older, with a history of cancer or hematological disorders?

Lenalidomide Side Effects

Lenalidomide causes significant hematologic toxicity (neutropenia and thrombocytopenia) and increases venous thromboembolism risk, particularly when combined with dexamethasone or chemotherapy, requiring prophylactic anticoagulation in multiple myeloma patients. 1

Hematologic Toxicities (Most Common and Dose-Limiting)

Myelosuppression

• Neutropenia is the most common grade 3-4 adverse event, occurring in 30-75% of patients depending on indication and dose 1

  • In MDS with del(5q): 75.4% at 10mg dose and 73.9% at 5mg dose experienced grade 3-4 neutropenia 1
  • In CLL: 49% experienced grade 3-4 neutropenia 1
  • G-CSF support is frequently required (used in 56.5% of MDS patients) to maintain dosing 1

• Thrombocytopenia occurs in 13-40% as grade 3-4 toxicity 1

  • More common in MDS patients (40.6% at 10mg, 33.3% at 5mg) 1
  • Dose reduction to 5mg daily is preferred over extending intervals when managing cytopenias 2

• Anemia develops in 11% as grade 3-4 toxicity 3

• Neutropenic fever occurs in approximately 6% of patients 1

Venous Thromboembolism (Critical Risk Requiring Prophylaxis)

Risk Profile by Disease

• Multiple myeloma patients have significantly elevated VTE risk when lenalidomide is combined with dexamethasone or chemotherapy 1

  • Deep vein thrombosis: 9% with lenalidomide vs 4% with placebo 3
  • Pulmonary embolism: 4% vs 1% with placebo 3
  • Prophylactic anticoagulation is mandatory: aspirin for standard risk, LMWH or warfarin for high-risk patients 1, 4

• MDS patients with del(5q) show 17% VTE incidence, typically occurring after 1 year of therapy 5

  • Routine prophylactic anticoagulation is not currently indicated in CLL patients 1

• CLL patients experience venous thromboembolic events, but routine prophylaxis is not recommended 1

Tumor-Related Reactions (Disease-Specific)

Tumor Flare Syndrome

• Occurs in 50-90% of CLL patients in first-line setting (mostly grade 1-2) 1
• Presents as painful lymph node enlargement, splenomegaly, low-grade fever, rash, and bone pain 1
• More frequent in patients with baseline lymph nodes >5 cm 1
• Typically grade 1-2 severity, manageable with supportive care 1

Tumor Lysis Syndrome

• Risk increases in patients with high lymphocyte counts before therapy 1
• Allopurinol prophylaxis recommended during cycle 1 (or first 3 cycles) 1

Cardiovascular Toxicities

• Atrial fibrillation: 18% vs 11% with placebo 3
• Cardiac complications noted particularly in combination regimens 1

Dermatologic Reactions

• Skin rash is common but typically mild to moderate 6, 7
• Various cutaneous adverse reactions documented including eruptions 7
• Generally manageable with supportive care 6

Gastrointestinal Effects

• Constipation, nausea, and other GI problems occur frequently 1, 6
• Generally mild to moderate severity 8

Neurologic Toxicity

• Peripheral neuropathy is rare with lenalidomide (unlike thalidomide) 4, 3
• One case of grade 3 motor neuropathy reported at 25mg/day in solid tumors 8
• This is a key advantage over thalidomide, which causes significant neuropathy 4, 3

Other Notable Toxicities

• Fatigue and asthenia are common 6, 7
• Infections occur with increased frequency, particularly in elderly patients 1
• Secondary malignancies have been reported 7
• Teratogenicity: lenalidomide is structurally related to thalidomide and carries teratogenic risk (inadequately documented but presumed) 3

Age-Related Considerations

• Older patients (≥65 years) have higher treatment discontinuation rates 1
  • Only 59% of patients ≥65 years completed planned therapy vs 90% of younger patients in CLL studies 1
• Increased risk of infections, fatigue, and DVT in elderly multiple myeloma patients 1

Critical Monitoring Requirements

• Complete blood counts weekly for first 8 weeks, then monthly 2
• Baseline liver function tests, then within 1-2 months and every 3-4 months thereafter 2
• Dose modifications based on ANC and platelet counts 2
• Avoid lenalidomide if ANC <500 cells/mcL or platelets <25,000 cells/mcL 2