In this article, we will discuss about Lenalidomide (Dosage). So, let’s get started.
Lenalidomide
Indications
Multiple Myeloma
Lenalidomide (REVLIMID®) in combination with dexamethasone is indicated for the treatment of patients with multiple myeloma (MM) who have received at least one prior therapy.
Myelodysplastic Syndromes
Lenalidomide (REVLIMID®) is indicated for the treatment of patients with transfusion-dependent anemia due to low-or intermediate-1-risk myelodysplastic syndromes (MDS) associated with a deletion S4 cytogenetic abnormality with or without additional cytogenetic abnormalities.
Dosage
Lenalidomide (REVLIMID®) should be taken orally at about the same time each day, either with or without food. Lenalidomide (REVLIMID®) capsules should be swallowed whole with water.
Multiple Myeloma
The recommended starting dose of Lenalidomide (REVLIMID®) is 25 mg once daily on Days 1-21 of repeated 28-day cycles. The recommended dose of dexamethasone is 40 mg once daily on Days 1-4,9-12, and 17-20 of each 28-duy eyele for the first cycles of therapy and then 40 mg once daily orally on Days 1-4 every 28 days. Treatment is continued or modified based upon clinical and laboratory findings.
Dose Adjustments for Hematologic Toxicities During Multiple Myeloma Treatment
Dose modification guidelines as summarised below, are recommended to manage Grade 3 or 4 neutropenia or thrombocytopenia or other Grade
3 or 4 toxicity judged to be related to lenalidomide
Platelet counts
Thrombocytopenia in MM
When Platelets – Recommended Course
Fall to <30,000 mcL – Interrupt Lenalidomide (REVLIMID®) treatment, follow CBC weekly
Return to ≥30,000 mcL – Restart Lenalidomide (REVLIMID®) at 15 mg daily
For each subsequent drop <30,000 mcL – Interrupt Lenalidomide (REVLIMID®) treatment
Return to ≥30,000 mcL – Resume Lenalidomide (REVLIMID®) 3 mg less than the previous dose Do not dose below 5mg daily
Absolute Neutrophil counts (ANC)
Neutropenia in MM
When Neutrophils – Recommended Course
Fall to <1000 mcL – lnterrupt Lenalidomide (REVLIMID®) Treatment, add G-CSF, follow CBC weekly
Return to ≥1000/mcL and neutropenia is the only toxicity – Resume Lenalidomide (REVLIMID®) at 25 mg daily
Return to ≥1000/mcL and if other toxicity – Resume Lenalidomide (REVLIMID®) 15 mg daily
For each subsequent drop <1000/mcL – Interrupt Lenalidomide (REVLIMID®) treatment
Return to ≥1000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg less than the previous dose. Do not dose below 5 mg daily
Other Grade 3/4 Toxicities in MM
For other Grade 3/4 toxicities judged to be related to Lenalidomide (REVLIMID®) hold treatment and restart at next lower dose level when toxicity has resolved to ≤ Grade 2.
Starting Dose Adjustment for Renal Impairment in MM
Since Lenalidomide (REVLIMID®) is primarily excreted unchanged by the kidney, adjustments to the starting dose of Lenalidomide (REVLIMID®) are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment and in patients on dialysis. Based on a pharmacokinetic study in patients with renal impairment due to nonmalignant conditions Lenalidomide (REVLIMID®) starting dose adjustment is recommended for patients with CLcr <60 mL/min. Non-dialysis patients with creatinine clearances less than 11 mL/min and dialysis patients with creatinine clearances less than 7 mL/min
have not been studied. The recommendations for initial starting doses for patients with multiple myeloma (MM) are as follows:
Starting Dose Adjustment for Renal Impairment in Multiple Myelona (Days 1-21 of each 28 day cycle)
Category – Renal Function (Cockcroft-Gault) – Dose
Moderate Renal Impairment – CLcr 30-60 mL/min – 10 mg every 24 hours
Severe Renal Impairment – CLcr <30 mL/min (not requiring dialysis) – 15 mg every 48 hours
End Stage Renal Disease – CLcr <30 mL/min (requiring dialysis) – 5 mg once daily. On dialysis days administer the dose following dialysis.
After initiation of Lenalidomide (REVLIMID®) therapy, subsequent Lenalidomide (REVLIMID®) dose modification should be based on individual patient treatment tolerance.
Myelodysplastic Syndrome
The recommende starting dose of Lenalidomide (REVLIMID®) 10 mg daily Treatment is continued or modified based upon clinical and laboratory findings.
Dose Adjustments for Hematologic Toxicities During MDS Treatment
Patients who are doses initially at 10 mg and who experience thrombocytopenia should have their dosage adjusted as follows:
Platelet counts
If thrombocytopenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS
If baseline ≥100,000/mcL
When Platelets – Recommended Course
Fall to <50,000/mcL – Interrupt Lenalidomide (REVLIMID®) treatment
Return to >50,000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily
If baseline <100,000/mcL
When Platelets – Recommended Course
Fall to 50% of the baseline value – Interrupt Lenalidomide (REVLIMID®) treatment
If baseline ≥60,000 mcL and returns to ≥50.000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily
If baseline <60,000/mcL and returns to ≥30,000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily
If thrombocytopenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS
When Platelets – Recommended Course
<30,000/mcL or <50.000/mcL with platelet transfusions – Interrupt Lenalidomide (REVLIMID®) treatment
Return to ≥30,000/mcL (without hemostatic failure) – Resume Lenalidomide (REVLIMID®) at 5 mg daily
Patients who experience thrombocytopenia at 5 mg daily should have their dosage adjusted as follows:
If thrombocytopenia develops during treatment at 5 mg daily in MDS
When Platelets – Recommended Course
<30,000 mcL or <50,000 mcL with platelet transfusions – Interrupt Lenalidomide (REVLIMID®) treatment
Return to ≥30,000 mcL (without hemostatic failure) – Resume Lenalidomide (REVLIMID®) at 25 mg daily
Patients who are dosed initially at 10 mg and experience neutropenia should have their dosage adjusted as follows:
Absolute Neutrophil counts (ANC)
If neutropenia develops WITHIN 4 weeks of starting treatment at 10 mg daily in MDS
If baseline ANC ≥1000/mcL
When Neutrophils – Recommended Course
Fall to <750 mcL – Interrupt Lenalidomide (REVLIMID®) treatment
Return to ≥1000/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily
If baseline ANC <1000/mcL
When Neutrophils – Recommended Course
Fall to <500 mcL – Interrupt Lenalidomide (REVLIMID®) treatment
Retum to ≥500/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily
If neutropenia develops AFTER 4 weeks of starting treatment at 10 mg daily in MDS
When Neutrophils – Recommended Course
<500/mcL for 27 days or <500/mcL associated with fever (≥38.5°C) – Interrupt Lenalidomide (REVLIMID®) treatment
Return to ≥500/mcL – Resume Lenalidomide (REVLIMID®) at 5 mg daily
Patients who experience neutropenia at 5 mg daily should have their dosage adjusted as follows:
If neutropenia develops during treatment at 5 mg daily in MDS
When Neutrophils – Recommended Course
<500/mcL for 27 days or <500/mcL (associated with fever ≥38.5°C) – Interrupt Lenalidomide (REVLIMID®) treatment
Return to ≥500/mcL – Resume Lenalidomide (REVLIMID®) 25 mg daily
Other Grade 3/4 Toxicities in MDS
For other Grade 3/4 toxicities judged to be related to Lenalidomide (REVLIMID®), hold treatment and restart at next lower dose level when toxicity has resolved to ≤Grade 2.
Starting Dose Adjustment for Renal Impairment in MDS:
Since Lenalidomide (REVLIMID®) is primarily excreted unchanged by the kidney, adjustments to the starting dose of Lenalidomide (REVLIMID®) are recommended to provide appropriate drug exposure in patients with moderate or severe renal impairment and in patients on dialysis. Based on a pharmacokinetic study in patients with renal impairment due to non-malignant conditions, Lenalidomide (REVLIMID®) starting dose adjustment is recommended for patients with CLcr<60 mL/min. Non-dialysis patients with creatitine clearances less than 11 mL/min and dialysis patients with creatinine clearances less than 11 mL/min and dialysis patients with creatinine clearances less than 7 mL/min have not been studied. The recommendations for initial starting doses for patients with myelodysplastic syndromes (MDS) are as follows:
Starting Dose Adjustment For Renal Impairment in Myelodysplastic Syndromes (Days 1 – 28 of each day cycle)
Category – Renal Function (Cockcroft-Gault) – Dose
Moderate Renal Impairment – CLcr 30-60 mL/min – 5 mg every 24 hours
Severe Renal Impairment – CLcr <30 mL/min (not requiring dialysis) – 2.5 mg every 24 hours
End Stage Renal Disease – CLcr < 30 mL/min (requiring dialysis) – 2.5 mg once daily. On dialysis days administer the dose following dialysis
After initiation of Lenalidomide (REVLIMID®) therapy, subsequent Lenalidomide (REVLIMID®) dose modification should be based on individual patient treatment tolerance.