Overcoming Proteasome Inhibitor-Refractory Multiple Myeloma With Elotuzumab, Bortezomib, Nelfinavir, and Dexamethasone

Multiple myeloma is a common plasma cell malignancy with a median overall survival of fewer than 10 years. Proteasome inhibitors comprise an important part of the treatment regimen for this disease. The present study reports the case of a 57-year-old man who experienced a second relapse of multiple myeloma 6 years after initial treatment with bortezomib, lenalidomide, dexamethasone (VRD) followed by autologous hematopoietic cell transplant. The first relapse had been successfully treated with VRD, but this approach failed to control his second relapse. Given the lack of response to VRD therapy and relapse while on bortezomib maintenance, the patient was deemed proteasome inhibitor-refractory and received a new treatment of elotuzumab, lenalidomide, and dexamethasone. Four and a half cycles were completed before the treatment was stopped due to grade 4 cytopenias. The patient received a novel combination of elotuzumab, bortezomib, nelfinavir, and dexamethasone. After six cycles, the serum M-protein level was improved to 0.6 g/dL and the kappa light chains dropped from 3.49 to 1.04 mg/dL. A bone marrow biopsy conducted after five treatment cycles demonstrated < 1% plasma cells by immunohistochemistry and achievement of minimal residual disease status. Overall, this case study suggests that proteasome inhibitor-refractory multiple myeloma may be successfully re-treated with proteasome inhibitors when co-administered with nelfinavir.