From the Guidelines
Lenalidomide can be effectively combined with CAR-T cell therapy to enhance treatment outcomes for certain blood cancers, as supported by the most recent and highest quality study 1. Lenalidomide, an immunomodulatory drug commonly used in multiple myeloma and certain lymphomas, works synergistically with CAR-T cells by creating a more favorable immune environment.
- Typically, lenalidomide (5-25 mg daily, depending on the specific condition and patient factors) may be used before CAR-T therapy to reduce tumor burden or after CAR-T infusion to enhance CAR-T cell persistence and function.
- The combination requires careful monitoring for cytokine release syndrome, which is a risk with CAR-T therapy, and for lenalidomide's side effects including cytopenias, fatigue, and thrombosis risk.
- Lenalidomide enhances CAR-T efficacy by stimulating T-cell proliferation, increasing cytokine production, and modulating the tumor microenvironment to be less immunosuppressive.
- It also helps overcome T-cell exhaustion that can limit CAR-T effectiveness. This combination approach is particularly promising for patients with relapsed/refractory multiple myeloma or certain B-cell malignancies where single-agent approaches have failed, though specific protocols should be determined by the treating oncologist based on individual patient factors and disease characteristics, as noted in 1 and 1. The management of immunotherapy-related toxicities is crucial, and guidelines have been established to ensure optimal patient outcomes, as discussed in 1 and 1. Overall, the combination of lenalidomide and CAR-T cell therapy has shown significant potential in improving treatment outcomes for certain blood cancers, and further research is needed to fully explore its benefits and risks.
From the Research
Interaction between Lenalidomide and CAR-T Cell Therapy
- The interaction between lenalidomide (Revlimid) and Chimeric Antigen Receptor T (CAR-T) cell therapy has been studied in several research papers 2, 3, 4, 5, 6.
- Lenalidomide has been shown to enhance the efficacy of anti-BCMA CAR-T treatment in relapsed/refractory multiple myeloma 2, 3.
- The combination of lenalidomide and CAR-T cell therapy has been found to be feasible and effective in the treatment of relapsed/refractory multiple myeloma, with a significant improvement in overall survival 4.
- Lenalidomide has also been shown to potentiate CAR T cell function in a concentration-dependent manner, increasing CAR T effector cytokine production and cytolytic activity 3.
- The use of lenalidomide maintenance after CAR-T therapy has been found to be safe and effective in patients with refractory/relapsed diffuse large B-cell lymphoma, with a significant improvement in overall survival 4.
Mechanism of Action
- Lenalidomide has been found to regulate T cell function, driving antimyeloma activity and altering the suppressive microenvironment, which may contribute to its ability to enhance CAR-T cell therapy 3.
- The combination of lenalidomide and CAR-T cell therapy has been found to increase CAR T cell counts in blood and significantly prolong animal survival in a murine model of multiple myeloma 3.
- Lenalidomide has also been found to delay the exhaustion of CAR-T cells, which may contribute to its ability to improve overall survival in patients with relapsed/refractory multiple myeloma 4.
Clinical Applications
- The combination of lenalidomide and CAR-T cell therapy has been found to be effective in the treatment of relapsed/refractory multiple myeloma, with a significant improvement in overall survival 2, 3, 4.
- Lenalidomide maintenance after CAR-T therapy has been found to be safe and effective in patients with refractory/relapsed diffuse large B-cell lymphoma, with a significant improvement in overall survival 4.
- The use of pomalidomide, a similar immunomodulatory drug, has also been found to be effective in combination with CAR-T cell therapy in patients with relapsed/refractory multiple myeloma or B-cell leukemia/lymphoma with extramedullary disease 5.