The Impact of Maintenance Lenalidomide and Depth of Response on the Mutational Status of the Myeloma Clone from Presentation to Relapse
John R JonesNiels WeinholdShweta S. ChavanCharlotte PawlynLorenzo MelchorDavid A. CairnsDavid C. JohnsonBrian WalkerChristopher P. WardellDil BegumSidra EllisCharlotte A. SmithAmy L. SherborneAmy PriceGordon CookMatthew JennerNigel H. RussellMark T. DraysonRoger G. OwenFaith E. DaviesMartin KaiserWalter M. GregoryGraham JacksonMel GreavesGareth J. Morgan
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Maintenance therapy
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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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Abstract Patients with high-risk smoldering multiple myeloma who received lenalidomide and dexamethasone for 9 months, followed by lenalidomide alone for an additional 15 months, demonstrated significantly improved overall and progression-free survival compared with patients who received no therapy.
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The field of multiple myeloma therapeutics has been an active one for many years, but perhaps no more so than in the past decade. The introduction of thalidomide, lenalidomide and bortezomib in the treatment of this disease highlights clinical advances made during this period. While these agents were initially utilized in the setting of relapsed and refactory disease, they are now part of the therapeutic armamentarium for transplant-eligible and transplant-ineligible patients with newly diagnosed multiple myeloma. The principles of management applied in the care of newly diagnosed multiple myeloma are reviewed in this article, along with the clinical studies supporting the use of thalidomide, lenalidomide and bortezomib in newly diagnosed multiple myeloma. Management of treatment-related side effects is also discussed, since it constitutes a critical element in the successful management of patients with this disease. Combination regimens utilizing thalidomide, lenalidomide and bortezomib are also highlighted, as these regimens are likely to play an increasingly important role in myeloma therapy in the future.
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Abstract Using the Canadian Myeloma Research Group Database, a retrospective study of 167 newly diagnosed, transplant‐ineligible patients with multiple myeloma (MM) that received lenalidomide‐dexamethasone as front‐line treatment was conducted to understand the impact of lenalidomide dosing. Starting dose modifications were common, 42% of patients started on lenalidomide <25 mg with normal renal function. During treatment course, 35% of patients required further dose reduction. Dose reductions in the first year did not have an impact on progression free survival or overall survival. Further studies need to be conducted to understand the impact of dosing strategies of anti‐MM agents in the real world.
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While in vitro hemolysis is a preanalytical interferent, in vivo hemolysis is a pathologic process requiring investigation. We present a case of an anemic patient with multiple myeloma undergoing chemotherapy with lenalidomide who had multiple serum samples drawn before and after chemotherapy treatment. Some of these samples showed hemolysis. This triggered further investigations to differentiate the cause of the hemolysis.Various laboratory tests and additional investigations were necessary to establish the root of the hemolytic process.Multiple laboratory tests and a rigorous review of the samples, time of collection, and laboratory results revealed that only samples collected shortly after lenalidomide administration showed hemolysis. This indicates that the chemotherapeutic agent itself was most likely the proximate cause of the in vivo hemolysis in a non-immune-mediated manner.Upon administration, chemotherapeutic agents, such as lenalidomide, can immediately induce transient hemolysis, which can be visualized as transiently pink-tinged serum samples.
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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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