Analysis of renal impairment in MM-003, a phase III study of pomalidomide + low - dose dexamethasone versus high - dose dexamethasone in refractory or relapsed and refractory multiple myeloma
K. WeiselMeletios Α. DimopoulosPhilippe MoreauMartha Q. LacyKevin SongM. DelforgeLionel KarlinHartmut GoldschmidtA. BañosAlbert OriolAdrián AlegreC. ChenMichèle CavoLaurent GarderetV. L. IvanovaJoaquín Martínez‐LópezStefan KnopXiaoyan YuKevin HongLars SternåsChristian JacquesMohamed H. ZakiJesús F. San Miguel
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Pomalidomide + low-dose dexamethasone is effective and well tolerated for refractory or relapsed and refractory multiple myeloma after bortezomib and lenalidomide failure. The phase III trial MM-003 compared pomalidomide + low-dose dexamethasone with high-dose dexamethasone. This subanalysis grouped patients by baseline creatinine clearance ≥ 30 − < 60 mL/min (n=93, pomalidomide + low-dose dexamethasone; n=56, high-dose dexamethasone) or ≥ 60 mL/min (n=205, pomalidomide + low-dose dexamethasone; n=93, high-dose dexamethasone). Median progression-free survival was similar for both subgroups and favored pomalidomide + low-dose dexamethasone versus high-dose dexamethasone: 4.0 versus 1.9 months in the group with baseline creatinine clearance ≥ 30 − < 60 mL/min (PKeywords:
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Optimal strategies for treating patients with very advanced relapsed and refractory multiple myeloma (RRMM) have not been clarified.A 80-year-old patient with RRMM experienced extramedullary relapse following treatment with bortezomib, lenalidomide and pomalidomide. However, he achieved very good partial remission after retreatment with lenalidomide.This report illustrates that patients with very advanced RRMM can still respond to prior therapy even after being exposed and refractory to several agents. Considering the depth or duration of response to prior treatment, "retreatment" may improve the outcome of frail RRMM.
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SúhrnAj napriek pokrokom v liečbe mnohopočetného myelómu, drvivá väčšina pacientov relabuje
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Thalidomide changed the treatment of patients with multiple myeloma, however, its effectiveness has been compromised due to its side effects. New strategies are needed to specifically target the challenges of multiple myeloma through innovative, more effective, and less toxic therapy. The new immunomodulatory (IMiDs) compounds are structural and functional analogs of thalidomide, which were designed to improve the immunomodulatory and anticancer properties and tolerability profiles. We review the development of second generation IMiDs, lenalidomide and pomalidomide, their immunomodulatory and tumoricidal effects, their mechanisms of action, as well as the influence of dexamethasone on their effect and pharmacological resistance. In conclusion, lenalidomide and pomalidomide demonstrate a powerful activity and they are highly effective and well-tolerated treatment options for patients with myeloma, used alone or in combination with dexamethasone.
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Treatment options for multiple myeloma dwindle with each relapse. There is no standard treatment for patients who relapse. Pomalidomide, an analogue of thalidomide and lenalidomide, has been authorised in the EU for the treatment of relapsed and refractory multiple myeloma after at least two previous lines of treatment including lenalidomide and bortezomib. Clinical evaluation of pomalidomide in this setting is based on an unblinded controlled trial in 455 patients who had already received several treatments, including lenalidomide. Nearly one-third of the patients were refractory to thalidomide.The patients were assigned to either high-dose dexamethasone or pomalidomide + low-dose dexamethasone. Pomalidomide prolonged median survival by at least 3 months. It has not been compared to thalidomide. The known adverse effects of pomalidomide include peripheral neuropathy, venous thrombosis, cutaneous disorders and neutropenia. Few cardiac disorders have been reported. Some drug-drug interactions can result in pomalidomide overdose. Pomalidomide is teratogenic. In practice, despite its adverse effects, third-line treatment with pomalidomide is an option for some patients who want to prolong survival by a few weeks: when myeloma is refractory to lenalidomide and thalidomide and their adverse effects were acceptable.
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The novel agents bortezomib and lenalidomide improve outcomes in multiple myeloma, yet most patients will relapse after exhausting treatment. Management of relapsed and refractory multiple myeloma (RRMM) is challenging owing to disease-, patient- and treatment-related factors, and new therapies for these patients are required. Pomalidomide (POM) is an immunomodulatory compound that has been recently approved in the USA for the treatment of RRMM after two prior therapies, including lenalidomide and bortezomib. POM has several potential mechanisms of action and has a unique pharmacokinetic profile. Several trials demonstrate the efficacy and safety of POM in RRMM, including subjects refractory to lenalidomide and bortezomib. Herein, POM is reviewed as a clinically active new treatment option for RRMM.
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Aim: To demonstrate the efficacy of pomalidomide for relapsed/refractory multiple myeloma (RRMM) following treatment in real-world, community practice using retrospective database analysis. Materials & methods: US-based community oncologists identified patients with RRMM treated with or without pomalidomide following first-line lenalidomide. Disease response (≥ very good partial response) and progression-free survival were compared. Results: Disease response was 78.6 and 51.7% for pomalidomide (n = 126) and nonpomalidomide cohorts (n = 174), respectively (p < 0.0001). Multivariate adjusted odds of response were 4.5-times greater for pomalidomide cohort (p < 0.0001). Median progression-free survival was not reached for pomalidomide cohort and 16.7 months for nonpomalidomide cohort (log-rank p < 0.01). Conclusion: Following lenalidomide induction in RRMM, pomalidomide is an effective treatment.
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The treatment options for patients with multiple myeloma (MM) remain limited. Immunomodulatory agents (IMiDs), such as thalidomide and lenalidomide, have changed the landscape in the treatment of patients with MM while newer IMiDs such as pomalidomide are showing promise in early clinical trials.This review focuses on the biologic rationales of IMiDs and the clinical results supporting their use in MM. It includes data on the new IMiD, pomalidomide and also explores the possible utility of combining IMiDs with other agents. A PubMed search and abstracts from oncology scientific meetings (ASCO and ASH) of articles related to IMiDs and MM was conducted.IMiDs have shown clinical activity as single agents and in combination. Thalidomide was the first in class drug. Lenalidomide has a better toxicity profile than thalidomide. Pomalidomide may overcome resistance to lenalidomide indicating differences in their mechanisms of action and resistance. Molecular biomarkers may allow us to identify patients who will respond to IMiDs.
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