From the Guidelines
Lenalidomide refractory multiple myeloma is defined as disease that has either failed to respond to lenalidomide therapy or has progressed during or within 60 days after completing lenalidomide treatment, as stated in the NCCN guidelines 1. This definition is crucial for clinical decision-making, as lenalidomide refractory patients typically require alternative treatment approaches.
- The development of refractoriness to lenalidomide involves multiple mechanisms, including alterations in cereblon protein, activation of alternative signaling pathways, and changes in the bone marrow microenvironment.
- Understanding lenalidomide refractoriness helps clinicians determine appropriate next-line therapies and predict treatment outcomes in multiple myeloma patients.
- According to the NCCN guidelines, patients with lenalidomide refractory multiple myeloma can be treated with ixazomib/pomalidomide/dexamethasone, which has shown promising preliminary response rates, especially in patients whose disease was refractory to both lenalidomide and a PI 1.
- The NCCN Panel has included ixazomib/pomalidomide/dexamethasone as a treatment option for patients with relapsed/refractory MM who have received at least 2 prior therapies including an IMiD and a PI and have shown disease progression on or within 60 days of completion of the last therapy 1.
- In contrast to older guidelines, the newer NCCN guidelines provide a more updated and comprehensive approach to managing lenalidomide refractory multiple myeloma, prioritizing the use of novel agents and combination regimens 1.
From the Research
Definition of Lenalidomide Refractoriness
- Lenalidomide refractoriness is defined as a lack of response or progression of disease while on lenalidomide treatment 2.
- The definition of lenalidomide refractoriness should not depend on the dose of lenalidomide to which the disease was considered refractory 2.
- Refractoriness to lenalidomide is an important factor determining the choice of therapy at first relapse in multiple myeloma (MM) 2.
Clinical Implications of Lenalidomide Refractoriness
- Patients refractory to lenalidomide have poorer outcomes compared to those who are not refractory, with shorter progression-free survival (PFS) and overall survival (OS) 3.
- Lenalidomide-refractory patients have a lower overall response rate (ORR) compared to the intent-to-treat population 3.
- The combination of lenalidomide and dexamethasone is effective and generally well tolerated in patients with renal impairment, but the starting dose of lenalidomide should be adjusted appropriately 4.
Treatment Options for Lenalidomide-Refractory Patients
- Novel agents such as daratumumab, pegylated liposomal doxorubicin, and isatuximab may offer better PFS and OS compared to traditional treatments 5.
- The addition of a second or third novel agent to either immunomodulatory (IMID) or proteasome inhibitor (PI) backbone may improve survival 5.
- Treatment outcomes in lenalidomide-refractory patients can vary depending on the specific treatment regimen and patient population 3.