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BACKGROUND: The increasing use of anti-CD38 monoclonal antibodies (αCD38 mAbs) for newly diagnosed or early relapsed multiple myeloma (MM), especially in non-transplant eligible patients, may lead to more patients developing αCD38 mAb-refractory disease earlier in the treatment course with fewer treatment options. PATIENTS AND METHODS: We analyzed the efficacy and safety of selinexor-based triplets (selinexor+dexamethasone [Sd] plus pomalidomide [SPd, n = 23], bortezomib [SVd, n = 16] or carfilzomib (SKd, n = 23]) in a subset of STOMP (NCT02343042) and BOSTON (NCT03110562) study patients treated previously with αCD38 mAbs. RESULTS: Sixty-two patients (median 4 prior therapies, range 1 to 11, 90.3% refractory to αCD38 mAb) were included. Overall response rates (ORR) in the SPd, SVd and SKd cohorts were 52.2%, 56.3%, and 65.2%, respectively. Overall response rate was 47.4% among patients who had MM refractory to the third drug reintroduced in the Sd-based triplet. Median progression-free survival in the SPd, SVd, and SKd cohorts was 8.7, 6.7, and 15.0 months, respectively, and median overall survival was 9.6, 16.9, and 33.0 months, respectively. Median time to discontinuation in the SPd, SVd, and SKd cohorts was 4.4, 5.9, and 10.6 months, respectively. The most common hematological adverse events were thrombocytopenia, anemia, and neutropenia. Nausea, fatigue, and diarrhea were primarily grade 1/2. Adverse events were generally manageable with standard supportive care and dose modifications. CONCLUSION: Selinexor-based regimens may offer effective and well-tolerated therapy to patients with relapsed and/or refractory MM who had disease previously exposed or refractory to αCD38 mAb therapy and could help address the unmet clinical need in these high-risk patients.
Biogenic amines (BAs) are basic nitrogenous low mass compounds with aliphatic (spermine, spermidine, putrescine, cadaverine), heterocyclic (e.g. tryptamine, histamine) or aromatic (e.g. tyramine) structure derived mainly from the decarboxylation of amino acids 1. They may be formed by the action of yeast, lactic acid bacteria or other microorganisms during alcoholic and malolactic fermentation 2. Most of BAs have strong physiological effects and play important biological role as source of nitrogen and precursors for synthesis of broad spectrum of biomolecules, such as hormones or nucleic acids 3. On the other hand BAs have been widely studied as potentially toxic substances, since excessive intake of BAs manifests as food poisoning 4. Moreover, BAs are potential precursors for the formation of carcinogenic N-nitroso compounds 5. In order to determine the concentrations of biogenic amines in biological matrices, techniques providing high resolution and sensitivity are demanded. To determine BAs is challenging because of strong polarity and no natural UV absorption nor fluorescence. Thus BAs must be pre or post-column derivatized before detection 6. Magnetic separation may be employed for isolation of a sample from complicated biological matrixes (food, body fluids) and may thus form the first separation and pre-concetration step prior to analysis to enhance an applied methodological approach 7. The main aim of the present study is synthesis of nanomaghemite core and its functionalization with ion-exchange resins (Dowex and sulfoxyethyl cellulose), which can provide binding sites for chosen BAs (Tyramine-Tyr; Putrescine-Put; Histamine-His; Cadaverine-Cad, Spermine-Spm and Spermidine-Spd respectively). Synthetic particles were finally employed for isolation and subsequent analysis by using ion-exchange chromatography.
- MeSH
- biogenní aminy * izolace a purifikace MeSH
- celulosa * analogy a deriváty MeSH
- chromatografie iontoměničová statistika a číselné údaje MeSH
- iontoměniče MeSH
- kovové nanočástice * MeSH
- magnetismus MeSH
- syntetické pryskyřice * MeSH
- výzkum MeSH
- železité sloučeniny chemická syntéza MeSH
- Publikační typ
- hodnotící studie MeSH
- práce podpořená grantem MeSH
