Treatment of 5q- Syndrome
Lenalidomide is the recommended first-line treatment for patients with 5q- syndrome who have transfusion-dependent anemia and have failed or are not candidates for treatment with hematopoietic growth factors. 1
Patient Selection and Treatment Algorithm
- For patients with isolated del(5q) without additional chromosomal abnormalities or excess blasts, with low or intermediate-1 IPSS score and transfusion-dependent anemia, lenalidomide is the treatment of choice 1
- Before initiating lenalidomide, patients should be evaluated for:
Dosing and Administration
- The recommended starting dose is 10 mg of lenalidomide daily for 21 days of a 28-day cycle, or 10 mg daily continuously 1
- Response assessment should be performed after 8-12 weeks (2-4 months) of treatment 1, 2
- Close monitoring of blood counts is mandatory during treatment, particularly in the first 6-8 weeks, due to the high risk of cytopenias 1, 3
Expected Treatment Outcomes
- Transfusion independence is achieved in 56-67% of patients 1, 2
- Cytogenetic responses occur in 50-76% of patients, with complete cytogenetic remission in 38-55% 1, 2
- Median time to response is approximately 4.6 weeks (range 1-49 weeks) 1, 2
- Responses are typically durable, with median duration of transfusion independence exceeding 2 years in many patients 2, 3
Management of Side Effects
- Grade 3-4 neutropenia occurs in 55-75% of patients 1
- Grade 3-4 thrombocytopenia occurs in 33-44% of patients 1
- Deep venous thrombosis occurs in 1.4-5.8% of patients 1
- G-CSF or GM-CSF may be used to prevent or reduce neutropenia 1
- Dose interruption or reduction may be necessary to manage cytopenias 2, 3
Special Considerations
- Patients with TP53 mutations have a significantly higher risk of transformation to AML and may be less responsive to lenalidomide 1
- For these patients, alternative therapeutic options should be considered, including hypomethylating agents or allogeneic hematopoietic stem cell transplantation 4
- The cumulative risk of AML progression in patients treated with lenalidomide is approximately 16.8% at 2 years and 25.1% at 3 years 1
Treatment After Lenalidomide Failure
- For patients who fail lenalidomide therapy, options include:
Monitoring During Treatment
- Complete blood counts should be monitored weekly during the first 8 weeks of treatment and at least monthly thereafter 1, 3
- Bone marrow examination with cytogenetics should be performed after 3-6 months to assess cytogenetic response 2, 3
- Regular assessment for signs of disease progression or transformation to AML is essential 5, 4