80,81 Lenaldomde s uto 2,000 tmes a lot more potent thathaldomde stmulatng the prolferatoof cells and uto one hundred tmes additional potent at ncreasng the release of2 and nterfero.77 Ths cell costmulatory actvty suggests that lenaldomde s able to act as aadjuvant to promote kind one cell medated anttumor mmune responses nvolvng each CD4helper cells and CD8 cytotoxc cells.73 The abty of lenaldomde to boost actvator prote1 and NF B actvty antgeprmed cellshas beeproposed as being a cell costmulatory mechansm, whch may well not only overcome cell anergy, but also potentates any nocell receptor medated sgnalng.78 addtoto bolsterng the adaptve mmune response, there s also ev dence that lenaldomde caenhance nnate mmunty and natural kler cell medated lyss of MM cells partcular va ts results o two productoby cells.
71,73,82 Lenaldomdehas selleck Anacetrapib beeshowto drectly potent ate apoptoss of MM cells va a few pathways.These nclude nhbtoof expressoof the cellular nhbtor of apoptoss prote2, potentatoof the actvtes of other apoptoss nducers which include TNF linked apoptoss nducng lgand, ncreased senstvty to Fas nducton, and enhanced caspase eight actvaton.78 Caspase eight, antegral element of Fas medated apoptoss, s sharply upregulated by lenaldomde.63 addton, dexa methasone actvates caspase 9 ndcatng that the two medication combnatogenerate dual sgnals capable of enhanced cell death.71 Lenaldomdehas beeassocated wth drect antprolferatve actvty aganst MM cells the absence of mmune cells or proapoptotc mechansms by nducng G1 growth arrest.74,78 mportantly, lenaldomde nhbts the prolferatoof malgnant B cells whe protectng usual CD34 progentor cells.
75 The varous mechansms of actoof lenaldomde are summarzed Fgure four.Clncal evdence for lenaldomde MM Newly dagnosed dsease Lenaldomde from this source s notet accredited for use patents wth prevously untreated dsease.having said that, a number of clncal studeshave reported promsng response and survval out comes ths grouof patents.Response charges and duratoof response Lenaldomde plus dexamethasone a phase research, whchhad a planned enrollment of 500 patents wth newly dagnosed MM but subsequently closed after 198 patents have been enrolled as a consequence of external data affectng the acceptabty with the management arm, patents were randomzed to lenaldomde 25 mg day plushgh dose dexa methasone, orhgh dose dexamethasone 40 mg day plus placebo.83 Lenaldomde was admnstered o28 of 35 days for 3 nductocycles, and the21 of 28 days as mantenance thereafter.
hgh dose dexamethasone was admnstered odays one four, 9 12, and 17 twenty durng nducton, and thedays 1 4 and 15 18 durng mantenance.Treatment method wth lenaldomde plushgh dose dexamethasoneelded aORR of 85.3% plus a CR fee of 22.1% versus remedy wthhgh dose dexamethasone alone.A 2nd phase randomzed study in contrast lenaldo mde plushgh dose dexamethasone wth lenaldomde plus very low

dose dexamethasone 445 patents wth newly dagnosed MM.