Carfilzomib, lenalidomide and dexamethasone for multiple myeloma – pro
The use of the combination of these drugs is the standard treatment in multiple myeloma. Clinical studies has shown its efficacy. This patient has already had treatment with Carfilzomib, Cytoxan and Dexamethasone.
Per Stewart et al (2015), “Lenalidomide plus dexamethasone is a reference treatment for relapsed multiple myeloma. The combination of the proteasome inhibitor carfilzomib with lenalidomide and dexamethasone has shown efficacy in a phase 1 and 2 study in relapsed multiple myeloma. In patients with relapsed multiple myeloma, the addition of carfilzomib to lenalidomide and dexamethasone resulted in significantly improved progression-free survival at the interim analysis and had a favorable risk-benefit profile.”
According to NCCN Multiple Myeloma Version 2.2020,
“Preferred Regimens for Previously Treated Multiple Myeloma are:
Carfilzomib/Lenalidomide/Dexamethasone based on the ASPIRE Study. Based on the data from this study, the NCCN Multiple Myeloma Panel has included the combination of carfilzomib with lenalidomide and dexamethasone as a preferred option for patients with relapsed/refractory myeloma (category 1).”
“Twice-weekly carfilzomib (27 mg/m2 ) with lenalidomide-dexamethasone (KRd) is a standard-of-care in relapsed or refractory multiple myeloma (RRMM). This phase 1b study evaluated KRd with once-weekly carfilzomib in RRMM. Patients received carfilzomib (30-minute infusion; 56 or 70 mg/m2 ) on days 1, 8, and 15; lenalidomide 25 mg on days 1-21; and dexamethasone 40 mg on days 1, 8, 15, and 22 (day 22 omitted for cycles 9+) of 28-day cycles.” (Biran et al 2019).
Finally per Landgren et al (2019), “A total of six distinct carfilzomib-based, PI/immunomodulator combination regimens have been evaluated in 12 clinical trials. Overall, treatment with these regimens has resulted in deep responses, including high rates of negativity for minimal residual disease. These deep responses have translated to long progression-free survival and overall survival rates. Efficacy results for these regimens have generally been consistent across subgroups defined by age, transplant eligibility, and cytogenetic risk. The safety profile of carfilzomib in NDMM is consistent with that observed in the relapsed-refractory MM setting. Clinical studies have found that carfilzomib-based combinations with immunomodulators are highly active with a favorable safety profile in NDMM. The carfilzomib, lenalidomide, and dexamethasone (KRd) drug backbone is a promising foundation for treatment strategies aimed at achieving long-term, deep responses (functional cures) in the frontline setting. Several ongoing studies are evaluating KRd, with or without anti-CD38 monoclonal antibodies.”
Biran, N., Siegel, D., Berdeja, J. G., Raje, N., Cornell, R. F., Alsina, M., Landgren, O. (2019). Weekly carfilzomib, lenalidomide, and dexamethasone in relapsed or refractory multiple myeloma: A phase 1b study. American journal of hematology, 94(7), 794802. doi:10.1002/ajh.25498.
Landgren, O. Sonneveld, P., & Jakubowiak, A., et al. (2019). Carfilzomib with immunomodulatory drugs for the treatment of newly diagnosed multiple myeloma. Leukemia, 33, 21272143, https://doi.org/10.1038/s41375-019-0517-6.
Stewart, A. K., Rajkumar, S. V., Dimopoulos, M. A., Masszi, T., Špicka, I., Oriol, A., ASPIRE Investigators (2015). Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. The New England journal of medicine, 372(2), 142152. doi:10.1056/NEJMoa1411321.