nowadays , patients with multiple myeloma ( mm ) live twice as long than they did twenty years ago . new drugs have prolonged overall survival ( os ) and progression - free survival ( pfs ) and improved the quality of patient 's life ( qol ) . although mm is still considered an incurable disease , the treatment philosophy has changed due to the introduction of novel agents . it is also proved that the depth of response determines the duration of pfs and os . researchers have shown that the pathological plasmocyte population in a specific patient is not monomorphic . according to the concept of clonal tides , one of the competing subclones becomes dominant , but during the treatment some of the other subclones might become prevalent . the induction should lead at least to partial remission ( pr ) . then in relatively young patients ( 6570 years ) autologous stem cell transplantation ( asct ) is conducted . asct is still considered the standard of care for frontline therapy in myeloma patients . for the last few years attempts have been made to deepen the response by consolidation and/or maintenance treatment . according to its definition , consolidation therapy is a short therapy carried out to improve the response quality , while maintenance treatment ( which should last much longer ) is mainly taken up to prolong the effects achieved before . in the light of reports on clonal heterogeneity in the myeloma population the double asct strategy was proposed to patients achieving less than a very good partial response ( vgpr ) after the first procedure . an italian trial under the leadership of marco ladetto was of key importance though it had few participants . it was one of the first clinical studies to demonstrate the benefits of novel agents used after asct . thirty - nine patients who achieved after asct at least very good partial remission ( vgpr ) were enrolled ( 20042007 ) . induction treatment included vad - like regimens ; therefore the patients were nave to novel drugs . in addition to regular evaluation of response , patients with tumour clone specific primers were studied by qualitative nested pcr and rq - pcr . meanwhile the molecular remission rate rose from 3% after asct to 18% after vtd . at the time of publication , in 2010 , no patient in complete molecular remission ( mr ) had relapsed . after a median follow - up of 42 months , andrew spencer presented the result of a phase iii randomised study on consolidation treatment with thalidomide and low doses of prednisolone ( tp ) . two hundred and sixty - nine patients who achieved at least stabilization of the disease after conventional chemotherapy were enrolled ( 20022005 ) . after the asct procedure , 129 patients were randomly assigned to receive prednisolone maintenance therapy and 114 to receive thalidomide plus prednisolone 12-month consolidation , but next prednisolone maintenance . after a median post - randomization follow - up of 3 years , 3-year pfs was 42% in the consolidation group and 23% in the  just maintenance  group ( p < 0.001 ) . overall survival rates were 86% in thalidomide patients and 75% in control patients ( p = 0.004 ) . there was no difference in patients survival 12 months after progression ( 79% vs. 77% , p = 0.237 ) . neurological toxicities were more common in the thalidomide arm ( 11 in 3/4 grade ) vs. none in the prednisolone arm . during the 2013 ash meeting the final analysis of the study after a median follow - up of 5.4 years , 2 patients per arm were lost from each arm . five - year pfs was 27% in the thalidomide group vs. 15% in the prednisolone group ( p = 0.005 ) . analogously , os rates in the two groups were 66% vs. 47% ( p = 0.007 ) . the authors observed that the patients who achieved vgpr or complete response ( cr ) after asct did not benefit from thalidomide consolidation . moreover , the patients required at least 8 months exposure to thalidomide to prolong pfs and/or os ( p < 0.001 ) . thalidomide after asct did not diminish the orr ( overall response rate ) when salvage therapy had to be introduced . recently the nordic myeloma study group ( nmsg ) published results of their randomized phase 3 trial assessing the efficacy of bortezomib monotherapy as consolidation treatment after asct . three hundred and seventy patients , who had not been exposed to bortezomib , were enrolled three months after single or tandem asct . the most common initial treatment was cy - dex ( cyclophosphamide and high doses of corticosteroids ) . one hundred and eighty - seven patients received bortezomib consolidation ( 20 doses ) . meanwhile the control group of 183 people was observed . at randomization there was no difference in response rates between the groups : 40% had achieved at least vgpr . the best response during the study was achieved in more - bortezomib treated patients : vgpr 71% vs. 57% ( p < 0.01 ) . the improvement from partial response ( pr ) to at least vgpr was shown by 57% in the bortezomib group vs. 36% in the observation group ( p = 0.007 ) . in the consolidation group pfs was 27 months while it was 20 months in the observation group ( p = 0.005 ) . after 3 years of follow - up , os was similar in both groups ( 80 ) . sensory peripheral neuropathy was reported by 57% of patients in the consolidation group vs. 24% in the control group . sensory neuropathy grade 3 or higher ( ctc scale ) was observed in 5% of bortezomib treated patients and 1% of controls . there were no other major differences in qol between the two groups . according to the authors , only the patients who had not achieved at least vgpr after asct derived significant benefits from bortezomib consolidation . it is worth mentioning that five - month treatment prolonged pfs by seven months . in 2012 , at the ash meeting , scientists from the ifm trial presented a retrospective analysis on the multidrug consolidation scheme vtd : bortezomib , thalidomide and dexamethasone . in contrast to the nordic trial , new drugs were used from the beginning of the treatment . the first cohort ( # 1 ) of 121 patients was given vtd in induction , then underwent asct , and in consolidation they were given the same scheme . the second cohort ( # 2 ) of 76 patients ( from the ifm-2007 - 02 trial ) was treated with vtd and asct without consolidation . the third cohort ( # 3 ) of 40 patients received upfront triplet bortezomib based combination ( vcd , vrd ) and underwent asct without consolidation . overall response rate equal to or higher than partial remission at completion of therapy was identical ( # 1 vs. # 2 vs. # 3 : 94% vs. 99% vs. 87% ) . nevertheless , the cr rate was significantly higher in the consolidation cohort ( # 1 ) : 53% vs. 36% vs. 35% ( p = 0.0001 ) . it is significant that after asct , cr rates were identical . in patients who received consolidation therapy the incidence rate of relapse was significantly lower : 21% vs. 55% vs. 32.5% ( p = 0.0001 ) . at the ash 2013 meeting , french scientists presented the results of a study on consolidation with vtd in myeloma patients with pr at completion of induction with vtd . one hundred and twenty - one patients who underwent vtd - asct - vtd from 2009 to 2011 were taken into the analysis . fifty - four patients achieved pr after vtd induction . at completion of consolidation , 33% achieved vgpr and 35% cr . thirty - five percent of the patients who did not benefit from asct ( 15 patients  still in pr after asct ) improved response after consolidation . the median time to progression ( ttp ) was less than 16 months in patients who did not improve their response after consolidation and was not reached in the group that benefited from vtd consolidation . three - year pfs was 18% in the first group and 58% in the second group . the median os was reached in neither of the groups . according to the authors , 68% of patients who achieved only pr after vtd induction did benefit from vtd consolidation . the gimema group conducted a phase 3 randomised prospective study comparing td ( thalidomide , dexamethasone ) to vtd ( bortezomib , thalidomide , dexamethasone ) as consolidation after asct . regardless of response to transplantation , three months after the second asct two consolidation courses were applied ( vtd vs. td ) . one hundred and sixty patients in every arm completed the treatment and were included in the analysis . after the consolidation phase , cr rates were 60.6% in vtd patients vs. 46.6% in td patients ( p = 0.012 ) , whereas after the second asct , cr rates were 48.7% vs. 40.4% ( p = 0.131 ) . post - transplantation consolidation treatment in myeloma patients in the vtd cohort median pfs was not reached , whereas in the td cohort it was 32 months . according to the authors , patients who most benefited from vtd consolidation therapy the vtd scheme in the consolidation phase was beneficial even in high cytogenetic risk groups ( del17p , t(4;14 ) ) . bortezomib attachment caused higher incidence of adverse effects , but they were usually of mild to moderate grade . in general , neurotoxicity was lower in the consolidation stage than in induction treatment . at ash 2012 , updated results of the gimema trial were announced . after a median follow - up of 52 months , a benefit from incorporation of bortezomib into consolidation was still relevant . in the vtd arm pfs was 56 months , and in the td arm it was 42 months ( p = 0.001 ) . moreover , short - term treatment with bortezomib did not influence the sensitivity of myeloma cells to bortezomib - based salvage therapy . terragna examined the molecular response in gimema patients and analysed 67 patients who achieved cr and near cr before consolidation beginning . forty - three percent of patients from the vtd group and 37.5% from the td group were pcr negative after the second asct . after consolidation treatment ( + 70 day ) minimal residual disease ( mrd ) negativity was achieved by 67% of vtd patients and 52% of td patients ( p = 0.05 ) . in 2011 , french scientists announced updated results of the phase 2 randomised trial ifm-2008 evaluating vrd combination applied in induction as well as in the consolidation phase . the patients received three 21-day vrd cycles ( bortezomib , lenalidomide , dexamethasone ) , proceeded to asct and then received two consolidation cycles ( the same schedule as in the induction phase ) followed by lenalidomide maintenance . considering the safety profile , the most important toxicities were : grade 2 polyneuropathy ( 13% ) , and grade 3/4 neutropenia ( 17% ) . novel agents besides bortezomib and lenalidomide are being introduced more courageously into the first line treatment . at the ash 2012 meeting , sonneveld presented the results of carfilzomib therapy of mm de novo trial . the authors reported on 40 patients registered to the first ( of three ) cohorts . thirty - nine patients completed 4 ctd courses ( carfilzomib , thalidomide , dexamethasone ) , underwent single asct , and in the consolidation phase received 4 ctd cycles with a reduced thalidomide dose ( 50 mg instead of 200 mg ) . after asct , 63% achieved at least vgpr ( 25% cr ) , and after the consolidation phase the vgpr or better response rate was 70% ( 35% cr ) . non - haematological side effects grade 3/4 were : deep vein thrombosis ( dvt ) 10% , skin rash 8% and polyneuropathy 17% . in 2013 , sonneveld announced at the ash meeting further data on their study : the patients of the first ( 50 patients ) and second ( 20 patients ) cohort . in cohort ii the dose of carfilzomib was escalated from 27 mg / m to 36 mg / m in the same schedule as described above . thirty - nine patients completed the protocol , with 19 still on treatment . the cr / scr rate ( which was 30% after asct ) increased to 49% after consolidation . the response was similar in standard and poor cytogenetic risk patients ( + 1q or t(4;14 ) or del17p ) . the safety profile was acceptable : non - haematological toxicities in 3 + 4 grades were less than 5% ( mainly infections and skin manifestations ) . in the united states under national cancer institute ( nci ) patronage consecutive total therapy ( tt ) modifications are being analysed : tt1 , tt2 , tt3 , and tt4 . in the tt2 phase consolidation varied and eventually used dpace ( dexamethasone , cisplatin , doxorubicin , cyclophosphamide , etoposide ) quarterly for 1 year . in the tt3 phase ii trial ( n = 303 ) consolidation used two cycles of vtd - pace ( bortezomib , thalidomide , dexamethasone ) . the authors of the tt analysis conclude that bortezomib added in the induction and consolidation phase improves the depth of response . in elderly and frail patients who are transplant ineligible italian scientists published the results of a phase ii trial with lenalidomide as consolidation treatment . median age was 75 years , and more than 30% of them had at least two comorbidities . the patients received 4 rp ( lenalidomide , prednisone ) cycles as induction treatment followed by 6 mpr ( melphalan , lenalidomide , prednisone ) consolidation cycles . the most frequent adverse events of grade 34 were cytopenias , infections and cutaneous reactions . mpr consolidation improved the response in 8 patients ( about 25% ) : in 2 patients from sd to pr , in 5 from pr to vgpr , in 1 from vgpr to cr . the authors concluded that melphalan dose reduction ( 50% compared to standard mpr studies ) did not influence the response rate but might have affected pfs : 18.4 months with rp - mpr compared with 2831 months with mpr - r . the most promising among them in the authors opinion are the following : a randomized phase iii trial under the auspices of the nci ( nci-2009 - 00521 ; nct00522392 ) has just ended ( viii 2007  viii 2013 ) ; the data are being analysed . the subject of the study is a comparison between vrd and vd consolidation . in induction the randomised phase iii trial ifm / dfci 2009 ( nct01191060 ) is still ongoing . this french - american study is designed to evaluate whether asct is still the gold standard in frontline mm therapy in the era of novel agents . a the patients receive 2 rvd ( lenalidomide , bortezomib , dexamethasone ) cycles , then stem cell collection is conducted , and 5 rvd consolidation cycles are given to the patients . in arm b ( also after two rvd induction cycles ) stem cell collection is conducted but then the patients undergo the asct procedure . a randomised phase iii trial under the auspices of bmt and nci is also still ongoing ( bmt ctn 0702 ; nct01109004 ) . the goal is to compare the effectiveness of single asct with consecutive consolidation treatment to double asct . prior to the first transplant , enrolled patients ( 750 patients ) are randomized to three cohorts . in the first one , patients undergo double asct . in the second cohort , after the first asct patients receive 4 rvd consolidation cycles . in the third cohort / control group , although the term  consolidation  has been present in myeloma treatment for years , its exact definition is still a matter of debate . it is commonly considered as therapy aimed at improvement of the depth of response after induction and asct . by design it should be a relatively short and intense therapy : composed of 24 cycles . in rajkumar 's opinion , so far , there have not been many large randomized trials dedicated to the consolidation phase . ideally , after uniform induction therapy and asct , patients should be randomized into homogeneous groups taking into account the cytogenetic profile . there are attempts to shift the procedure to the second line treatment . in the light of current knowledge on genetic heterogeneity of particular myeloma subclones , we can guess that attaching drugs that were not applied in previous therapy phases might help in eliminating distinct subclones . so far , there are not sufficient data to establish that consolidation treatment prolongs os in myeloma patients . as a matter of fact , the results of ongoing trials are impatiently awaited to establish the value of consolidation treatment . in view of the lack of sufficient evidence of the value of consolidation treatment , it is not recommended in every - day practice . however , more and more clinical centres apply consolidation within multicentre or local clinical trials . it seems that in the near future it might become an element of routine therapy in myeloma . in the authors opinion , consolidation is a very promising treatment element : a chance to improve the depth of response and to prolong os . but before this happens , we will have to answer many questions : who would benefit from consolidation ? how long should consolidation last ? what drugs should be used in the consolidation scheme ?
although multiple myeloma ( mm ) is still considered an incurable disease , the treatment philosophy is changing due to the introduction of novel agents . 
 standard treatment consists of an induction phase and autologous stem cell transplantation in patients under 6570 years . 
 prolonged treatment ( consolidation and/or maintenance ) is being introduced in many countries . 
 we present a review of clinical trials dedicated to consolidation treatment in multiple myeloma . 
 bortezomib , lenalidomide and carfilzomib in different combinations were tested in the trials mentioned below . 
 although they did not prolong overall survival , the data are very promising . 
 three very important large clinical trials are still in progress . 
 the results might help to establish the actual value of consolidation treatment .