Real World Treatment Patterns and Toxicity Among Elderly Patients with Multiple Myeloma
Jesus D. Gonzalez‐LugoAna Acuña-VillaorduñaJoshua HeislerNiyati GoradiaDaniel ColeMateo Mejía SaldarriagaAditi ShastriGurbakhash KaurIra BraunschweigNoah KornblumAmit VermaMurali JanakiramIoannis Mantzaris
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The combination of bortezomib (Velcade, PS-341) and lenalidomide (Revlimid) for the treatment of multiple myeloma was proved by USA Food and Drug Administration in 2006. Lenalidomide prevents the proliferation of multiple myeloma cells through binding to cereblon and promoting the ubiquitinational degradation of IKZF1 (Ikaros)/IKZF3 (Aiolos). However, the proteasome inhibitor bortezomib would inhibit the ubiquitinational degradation of IKZF1/IKZF3. How bortezomib could not block the antiproliferative effect of lenalidomide on multiple myeloma cells, which is the paradoxical pharmacological mechanisms in multiple myeloma. In this review, we summarized recent advances in molecular mechanisms underlying the combination of bortezomib and lenalidomide for the treatment multiple myeloma, discussed the paradoxical pharmacological mechanisms of lenalidomide and bortezomib in the treatment of multiple myeloma.
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Combination of lenalidomide with dexamethasone (LD) is of high effectiveness for treatment of multiple myeloma (MM), resulting in an improved overall survival, response rate, and time to progression in relapsed or refractory MM. Adverse events, especially venous thromboembolism, were generally well tolerated. In addition, lenalidomide plus dexamethasone is a potential therapy in maintenance of myeloma.
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In some patients with multiple myeloma, extramedullary masses may be present at diagnosis or may develop during treatment. Recently, multiple myeloma has been treated using newer therapeutic regimens based on thalidomide and bortezomib. Using these drugs, positive responses to treatment, not found with conventional antineoplastic agents, have been reported along with an improvement in patient outcome. In the present study, we report on three patients with extramedullary masses associated with multiple myeloma. Although all three patients were treated with bortezomib, it was ineffective against the extramedullary masses and the clinical course of the disease differed between the three patients. We propose that the effects of bortezomib on extramedullary masses may differ from case to case and may not be evident in cases of severe disease. Also, the effects of bortezomib may not be evident in the case of myeloma cells that have left the bone marrow microenvironment, similar to thalidomide. In addition, resistance to bortezomib may manifest as extramedullary masses. (160 words in the body of abstract).
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Objective The aim of this study was to assess the effect of Bortezomib on serum cystatin-C(Cys-C)in multiple myeloma and whether Cys-C can monitor tumor load.Methods We measured serum Cys-C and β2-microglobulin in multiple myeloma patients and 20 healthy controls pre-and post-Bortezomib therapy.Results Multiple myeloma patients had higher Cys-C and β2-microglobulin levels compared with healthy controls(P0.05).Treatment with Bortezomib produced a significant reduction of cystatin-C and β2-microglobulin,mainly in relapsed patients(P0.05).Conclusion Treatment with Bortezomib can significantly reduce the Cys-C levels,which can be regarded as the potential indicator to monitor tumor load,and β2-microglobulin levels of multiple myeloma patients.
Beta-2 microglobulin
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Myeloma protein
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Lenalidomide is known to be an effective therapy for multiple myeloma and for myelodysplastic syndrome (MDS) with isolated del(5q). We report the case of a patient simultaneously diagnosed with multiple myeloma and myelodysplastic syndrome with isolated del(5q) who was treated successfully with lenalidomide, bortezomib, and dexamethasone. The treatment achieved a stringent complete response of multiple myeloma and a hematologic and cytogenetic response of MDS in three months. Our experience suggests that standard myeloma induction regimens including lenalidomide and a proteasome inhibitor may be considered for treatment of concurrently diagnosed multiple myeloma and MDS with isolated del(5q) and are safe to use in select patients.
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