Clinical Scorecard: Enhancing Lenalidomide Treatment in Patients with Renal Impairment: Insights from the Prospective REMNANT Study on Renal Outcomes in Newly Diagnosed Multiple Myeloma Candidates for Transplantation

At a Glance

Key Highlights

• Renal impairment is a myeloma-defining event and significantly reduces overall survival, especially with acute kidney injury at diagnosis.
• Standard lenalidomide dosing recommends reductions based on eGFR, but recent data suggest higher doses may be safe and improve renal recovery.
• The REMNANT study evaluates higher-than-label lenalidomide doses (25 mg or 15 mg) in TE-NDMM patients with renal impairment, showing safety and promising renal and overall response rates.

Guideline-Based Recommendations

Diagnosis

• Assess renal function using eGFR (CKD-EPI formula) at diagnosis in MM patients.
• Evaluate serum free light chain (FLC) levels aiming for early reduction below 500 mg/L to promote renal recovery.
• Use IMWG renal response criteria for monitoring renal improvement.

Management

• Lenalidomide-based induction (VRd regimen) is standard for TE-NDMM patients.
• Dose lenalidomide at 25 mg/day on days 1–14 of a 21-day cycle for patients with eGFR ≥30 mL/min/1.73m2.
• Use 15 mg/day lenalidomide on days 1–14 for patients with eGFR <30 mL/min/1.73m2, including dialysis-dependent patients, as per REMNANT study protocol.
• Administer bortezomib subcutaneously and dexamethasone orally as per protocol.
• Provide herpes zoster prophylaxis for all patients.
• Use thromboprophylaxis with low-dose aspirin or direct oral anticoagulants based on thrombotic risk.

Monitoring & Follow-up

• Monitor adverse events grade ≥2 related to lenalidomide requiring intervention.
• Assess disease response at each cycle using serum M-protein and serum free light chain parameters.
• Adjust lenalidomide dosing at the start of each cycle based on renal function.

Risks

• Increased systemic exposure to lenalidomide with worsening renal function may increase toxicity risk.
• Potential for adverse events requiring dose modification or intervention.
• Thrombotic risk necessitates appropriate prophylaxis.

Patient & Prescribing Data

Transplant-eligible newly diagnosed multiple myeloma patients with renal impairment, including those on dialysis.

Higher-than-label lenalidomide doses (25 mg for eGFR ≥30 and 15 mg for eGFR <30) were well tolerated and may facilitate faster serum free light chain reduction and renal recovery.

Clinical Best Practices

• Evaluate renal function precisely at baseline and before each treatment cycle to guide lenalidomide dosing.
• Consider higher lenalidomide doses than currently recommended in patients with moderate to severe renal impairment under close monitoring.
• Implement prophylaxis for herpes zoster and thrombosis tailored to patient risk factors.
• Use modified IMWG criteria incorporating serum markers for disease and renal response assessment.
• Ensure multidisciplinary care including nephrology input for patients with significant renal impairment.

References

• ClinicalTrials.gov NCT04513639