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Bulletin Du Cancer Sep 2017Pomalidomide is a second-generation immunomodulatory drug (IMID). Its efficiency overtakes its predecessors' (thalidomide, lenalidomide), with less toxicity. It is...
Pomalidomide is a second-generation immunomodulatory drug (IMID). Its efficiency overtakes its predecessors' (thalidomide, lenalidomide), with less toxicity. It is indicated in the treatment of refractory or relapsed multiple myeloma, associated to dexamethasone. It is available in France since 2013, following the results of different studies.
Topics: Clinical Trials as Topic; Humans; Immunologic Factors; Multiple Myeloma; Thalidomide
PubMed: 28583668
DOI: 10.1016/j.bulcan.2017.04.005 -
The Lancet. Oncology Dec 2016
Topics: Antineoplastic Agents, Immunological; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Humans; Sarcoma, Kaposi; Skin Neoplasms; Thalidomide; Treatment Outcome
PubMed: 27839961
DOI: 10.1016/S1470-2045(16)30581-2 -
The Oncologist Mar 2015On August 5, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pomalidomide in combination with dexamethasone for the treatment of... (Review)
Review
The European medicines agency review of pomalidomide in combination with low-dose dexamethasone for the treatment of adult patients with multiple myeloma: summary of the scientific assessment of the committee for medicinal products for human use.
On August 5, 2013, a marketing authorization valid throughout the European Union (EU) was issued for pomalidomide in combination with dexamethasone for the treatment of adult patients with relapsed and refractory multiple myeloma (MM) who have received at least two prior treatment regimens, including both lenalidomide and bortezomib, and have demonstrated disease progression on the last therapy. Pomalidomide is an immunomodulating agent. The recommended starting dose of pomalidomide is 4 mg once daily taken on days 1-21 of repeated 28-day cycles. The main evidence of efficacy for pomalidomide in MM was based on a phase III multicenter, randomized, open-label study (CC-4047-MM-003) in which pomalidomide plus low-dose dexamethasone therapy (POM+LoDEX) was compared with high-dose dexamethasone alone (HiDEX) in previously treated adult patients with relapsed and refractory multiple myeloma who had received at least two prior treatment regimens, including both lenalidomide and bortezomib, and had demonstrated disease progression on the last therapy. For the intent-to-treat population, median progression-free survival based on International Myeloma Working Group criteria was 15.7 weeks (95% confidence interval [CI]: 13.0-20.1) in the POM+LoDEX group versus 8.0 weeks (95% CI: 7.0-9.0) in the HiDEX group (log-rank p value <.001). Overall survival (secondary endpoint) was also different in the two treatment groups (hazard ratio 0.53 [95% CI: 0.37-0.74]). The most commonly reported adverse reactions to pomalidomide in clinical studies were anemia (45.7%), neutropenia (45.3%) and thrombocytopenia (27%), fatigue (28.3%), pyrexia (21%), peripheral edema (13%), and infections including pneumonia (10.7%). Peripheral neuropathy adverse reactions were reported in 12.3% of patients, and venous embolic or thrombotic (VTE) adverse reactions were reported in 3.3% of patients. Pomalidomide is expected to be teratogenic. This paper summarizes the scientific review of the application leading to approval in the EU. The detailed scientific assessment report and product information, including the summary of product characteristics, are available on the EMA website (http://www.ema.europa.eu).
Topics: Antineoplastic Combined Chemotherapy Protocols; Boronic Acids; Bortezomib; Dexamethasone; Disease Progression; Drug Resistance, Neoplasm; Europe; Humans; Lenalidomide; Multiple Myeloma; Neoplasm Recurrence, Local; Pyrazines; Survival Rate; Thalidomide
PubMed: 25673103
DOI: 10.1634/theoncologist.2014-0073 -
Future Oncology (London, England) Feb 2022To demonstrate the efficacy of pomalidomide for relapsed/refractory multiple myeloma (RRMM) following treatment in real-world, community practice using retrospective...
To demonstrate the efficacy of pomalidomide for relapsed/refractory multiple myeloma (RRMM) following treatment in real-world, community practice using retrospective database analysis. 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. 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). Following lenalidomide induction in RRMM, pomalidomide is an effective treatment.
Topics: Angiogenesis Inhibitors; Female; Humans; Lenalidomide; Male; Middle Aged; Multiple Myeloma; Neoplasm Recurrence, Local; Progression-Free Survival; Retrospective Studies; Thalidomide
PubMed: 34787472
DOI: 10.2217/fon-2021-1176 -
Leukemia Research Jun 2017Oprozomib (OPZ or ONYX 0912) is an irreversible, orally administered proteasome inhibitor (PI) and an analog of carfilzomib. We set out to determine the anti-angiogenic... (Review)
Review
Oprozomib (OPZ or ONYX 0912) is an irreversible, orally administered proteasome inhibitor (PI) and an analog of carfilzomib. We set out to determine the anti-angiogenic effect of OPZ using the choriollantoic membrane/feather bud (CAM/FB) model and its anti-MM effects using MM xenograft models (LAGκ-1A, LAGλ-1). OPZ significantly reduced blood vessel formation, endothelial gene and protein expression using the CAM/FB assay. In vivo, we determined the anti-MM effects of OPZ, dexamethasone (Dex) and pomalidomide (Pom) and showed that the combinations of two drugs (OPZ+Dex or OPZ+Pom) showed marked anti-MM effects when compared to monotherapy. Pom+Dex and the triplicate combination (OPZ+Pom+Dex) showed more anti-MM effects when compared to the doublets of either OPZ+Dex or OPZ+Pom; continued treatment with all three drugs (OPZ+Pom+Dex) was superior when compared to Pom+Dex, in both MM xenograft models tested. These studies show that OPZ has anti-angiogenic effects, and that the combination of OPZ, Dex and Pom produces greater anti-MM effects in vivo when compared to any of the doublet combinations. These studies provide further support for clinical trials evaluating OPZ in combination with Pom and Dex.
Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Humans; Male; Mice; Mice, SCID; Multiple Myeloma; Neovascularization, Pathologic; Oligopeptides; Thalidomide; Xenograft Model Antitumor Assays
PubMed: 28288323
DOI: 10.1016/j.leukres.2017.03.002 -
Nihon Rinsho. Japanese Journal of... Jul 2016
Topics: Angiogenesis Inhibitors; Humans; Multiple Myeloma; Thalidomide
PubMed: 30615392
DOI: No ID Found -
European Journal of Medicinal Chemistry Sep 2022Overexpression of histone deacetylase 8 (HDAC8) is associated with various diseases such as cancer. Thus, compounds that can modulate HDAC8 levels have therapeutic...
Overexpression of histone deacetylase 8 (HDAC8) is associated with various diseases such as cancer. Thus, compounds that can modulate HDAC8 levels have therapeutic potential for these diseases. Based on the proteolysis targeting chimera (PROTAC) strategy, we designed and synthesized a series of HDAC8 degraders by tethering an HDAC6/8 dual inhibitor with pomalidomide (a cereblon ligand). Among them, compound ZQ-23 exhibited significant and selective degradation of HDAC8 with DC of 147 nM and D of 93%, and exhibited no effects on HDAC1 and HDAC3. Interestingly, we found that the degradation of target protein started at ∼2 h after treatment with ZQ-23 and the maximal degradation effect was achieved at 10 h. The HDAC8 level was partially recovered within 24 h. In addition, ZQ-23 had no degrading effects on HDAC1 and HDAC3 at all concentrations, but could dose-dependently increase the levels of acetylated SMC-3 (HDAC8 substrate). Mechanism study demonstrated that ZQ-23 degraded HDAC8 through the ubiquitin-protease pathway, rather than lysosome system. Collectively, these results suggest that ZQ-23 represents a novel PROTAC-based HDAC8 degrader worthy of further investigation.
Topics: Histone Deacetylase Inhibitors; Histone Deacetylases; Proteolysis; Thalidomide
PubMed: 35759908
DOI: 10.1016/j.ejmech.2022.114544 -
Leukemia Mar 2017
Topics: Anemia; Humans; Immunologic Factors; Primary Myelofibrosis; Thalidomide
PubMed: 27932792
DOI: 10.1038/leu.2016.348 -
Nihon Yakurigaku Zasshi. Folia... Sep 2016
Review
Topics: Animals; Clinical Trials as Topic; Drug Resistance, Neoplasm; Food-Drug Interactions; Humans; Kidney Function Tests; Thalidomide
PubMed: 27581964
DOI: 10.1254/fpj.148.154 -
European Journal of Haematology May 2019The presence of plasmacytomas (Ps) in patients with multiple myeloma (MM) is associated with a poor outcome, both in patients treated conventionally and in patients...
OBJECTIVE
The presence of plasmacytomas (Ps) in patients with multiple myeloma (MM) is associated with a poor outcome, both in patients treated conventionally and in patients treated with novel agents. Two types of plasmacytomas have being recognized: paraskeletal plasmacytomas (PPs) and extramedullary plasmacytomas (EMPs), being the incidence of EMPs lower but with worse prognosis. Our aim has been to analyze the efficacy of the pomalidomide-dexamethasone combination in this patient profile.
METHOD
In the present study, the efficacy of pomalidomide and dexamethasone in 21 patients from nine hospitals of Catalonia (Spain), with relapsed or refractory MM and Ps, was analyzed. For this purpose, we describe the evolution of paraprotein in serum and urine and the size of plasmacytomas during treatment with pomalidomide-dexamethasone.
RESULTS
While 34% of the patients achieved a paraprotein response, only two patients with PPs (9%) responded (RC and PR). There were no responses among patients with EMPs. The median progression-free survival from the start of treatment with pomalidomide/dexamethasone was only 1.7 months and the median overall survival of 4.5 months.
CONCLUSION
In conclusion, pomalidomide and dexamethasone has limited efficacy in patients with advanced MM and soft-tissue plasmacytomas.
Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Dexamethasone; Drug Resistance, Neoplasm; Female; Humans; Male; Middle Aged; Multimodal Imaging; Multiple Myeloma; Neoplasm Recurrence, Local; Plasmacytoma; Soft Tissue Neoplasms; Thalidomide
PubMed: 30719772
DOI: 10.1111/ejh.13217