fifty five The ORR was 41% for patents recevng bortezomb versus 22% for thaldomde.Smarly, bortezomb monotherapyelded ahgher ORR thasngle agent dexamethasone the relapse settng and ahgher CR fee.56 Bortezomb was assocated wth mproved TTcompared wth sngle agent dexamethasone and oneear survval.A recent update showed aORR of 43% and a medaOS of 29.eight months.57 There s also evdence showng ncreased response rates for bortezomb combnatowth dexamethasone.25,58,59 combnatowth minimal dose melphalaand dexamethasone, bortezombelded aORR of 69%, ncludng 29% wth VGPR or greater.60 The current FDA approval of the novel bortezomb combnatowth pegylated lposomal doxorubcwas based oa prorty revew of nterm data from a phase clncal tral, whch showed that ths combnatosgnfcantly extended TTcompared wth bortezomb alone.
OS was also sgnfcantly mproved compared wth bortezomb alone.61 Bortezomb s at present beng nvestgated the relapsed or refractory dsease settng combnatowth a lot of novel agents, ncludng tanespmycn, perfosne, and these details oral vornostat and relatedhstone deacetylase nhbtors.57,62,64,65 mportantly, a four drug combnatohas showpartcular promse, wth a phase tral of bortezomb, melphalan, prednsone, and thaldomdeeldng aORR of 67%, ncludng 43% wth a VGPR.66 Cortcosterods and alkylatng agentshave formed the manstay of treatment for decades and contnue for being utilized combnatoregmens, exactly where medicines wth dfferent mechansms of actocaoffer mportant synergstc results.on the other hand, much more effectve targeted therapes are begnnng to emerge as a result of amproved understandng from the bology of MM.
13 The ratonal improvement of those therapes, whch nclude lenaldomde, thaldomde, and bortezomb, provdes aopportunty to deal with patents even more effectvely wth fewer sde results whe amng selleckchem for durable responses.Wth mechansms of actothat are dstnct from cytotoxc chemotherapes, these novel therapies wl contnue to offer synergstc effects wth convetonal remedies and so offer potental survval beneft.Thaldomde was the frst mmunomodulatory drug to show sgnfcant actvty newly dagnosed and relapsed dsease, partcularly combnatowth dexamethasone.ts ant MM effects are drected by multple mechansms that nclude antangogeness, mmunomodulatoof the tumor mcroenvronment, and nductoof apoptoss tumor cells.49however, addtotohavng teratogenc potental, thaldo mde s assocated wth quite a few possble sde effects, ncludng sedaton, fatgue, skrash, and constpaton, less commosde effects nclude bradycarda, mpotence, neutropena, dysmenorrhea, and edema.
mportantly, long-term use cacause perpheral neuropathy.9

addtoto neuropathy, perhaps essentially the most worryng sde effecVTE, ncludng deevethrom boss, whch partcularly problematc combna towth multagent chemotherapy and dexamethasone.67,68 Lenaldomde Like a indicates of enhancng the mmunomodulatory effects and overcomng the nonhematologcal adverse events of thaldo mde, analogs which include lenaldomdehave beedeveloped.