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Ndmm november2014 excerpt

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NDMM

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Ndmm november2014 excerpt

  1. 1. Lorena Tonarelli MSc, BSc (Hons) Healthcare journalist and medical writer NDMM - excerpt       1   MM-­020  (FIRST®  Study)   A   phase   III,   randomised,   multicentre,   open   label   trial,   MM-­020   (Benboubker   et   al,   New  England  Journal  of  Medicine  2014)  aimed  to  compare  the  efficacy  and  safety  of   LEN  +  LoDEX  given  continuously  (Ld),  LEN  +  LoDEX  administered  in  18  cycles  (72   wks;;  Ld18)  and  MPT  given  in  12  cycles  (72  wks).  One  of  the  largest  of  its  kind,  MM-­ 020  was  carried  out  in  246  centres  in  18  countries,  including  North  America,  Europe,   Asia  and  the  Asia  Pacific  region.     Design  and  methods   One  thousand,  six  hundred  and  twenty-­three  patients,  either  older  than  65  years  of   age  or  ineligible  for  transplant,  were  randomised  1:1:1  to  the  three  study  arms.  Those   in  the  lenalidomide  arms  received  LEN  25  mg  daily  on  days  1  to  21  and  low  dose   DEX  at  40  mg  weekly.  Melphalan  was  given  in  the  MPT  arm  at  a  dose  (0.25  mg/kg   on  days  1  to  4),  similar  to  that  administered  in  IFM-­9906  (Facon  et  al,  The  Lancet   2007),   which   was   a   licensing   study   for   MPT.   Patients   older   than   75   years   had   reduced  doses  of  dexamethasone,  thalidomide  and  melphalan  (20  mg  weekly,  100   mg,  and  0.2  mg  per  kg,  respectively).  Stratification  was  by  age  (≤  75  years  vs.  >  75   years),   country   and   ISS   stage   (I   or   II   vs.   III).   Patients   were   followed   up   until   progressive  disease  or  unacceptable  toxicity,  and  then  for  OS  and  subsequent  anti   myeloma  treatment.  All  had  thromboprophylaxis,  which  consisted  of  aspirin  70  to  100   mg,   although   patients   with   previous   DVT   or   PE   could   receive   bisphosphonates   or   other  supportive  care  at  the  investigators’  discretion.     Inclusion  criteria   Patients   had   0   to   2   ECOG   performance   status,   as   well   as   symptomatic   and   measurable   untreated   multiple   myeloma   as   defined   by   IMWG   criteria.   Renal   impairment  was  allowed  into  the  study,  but  dialysis  was  excluded.     Study  endpoints   The   primary   endpoint   was   PFS.   Secondary   endpoints   included   OS,   ORR,   DOR,   TTR,   TTF,   2nd   AMT,   safety   and   HRQoL.   Time   to   progression   and   PFS2   (the   time   from   randomisation   to   time   of   objective   disease   progression   after   the   next   line   of   treatment,   death   from   any   cause,   or   start   of   third-­line   therapy)   were   exploratory   endpoints.  The  primary  comparison  was  between  continuous  LEN  and  MPT.    
  2. 2. Lorena Tonarelli MSc, BSc (Hons) Healthcare journalist and medical writer NDMM - excerpt       2     Patient  disposition   As  of  May  24th  2013,  the  study  median  follow-­up  was  37  months,  at  which  time  23%   of  patients  were  still  on  continuous  Ld  and  39%  had  received  it  for  over  two  years.   More   patients   on   continuous   therapy   reached   72   weeks   of   treatment   (55%)   than   patients  on  MTP  (45%)  or  Ld18  (52%).  The  rate  of  discontinuations  due  to  AEs  was   lower  in  the  continuous  arm  than  in  the  MPT  arm  (11  vs.  14%).  The  median  duration   of  treatment  was  18.4  months  with  continuous  therapy,  versus  15.4  and  16.6  months   with  the  standard  of  care  and  Ld18,  respectively.       Results   Patient   characteristics   were   similar   across   treatment   groups.   The   median   age   (73   years)   was   slightly   higher   than   in   studies   IFM99-­06   and   VISTA   (San   Miguel   et   al,   New   England   Journal   of   Medicine   2008).   The   study   population   was   a   good   representation  of  NDMM  patients  in  primary  care;;  35%  per  cent  were  older  than  75   years   of   age,   8   to   10%   had   CrCl   <   30   mL/min,   and   17   to   20%   had   high-­risk   cytogenetics  (i.e.,  t(4;;14),  t(14;;16)  or  del(17p)).     Efficacy   The  median  PFS  (primary  endpoint)  was  25.5,  21.2  and  20.7  months  for  continuous   Ld,  MPT  and  Ld18,  corresponding  to  a  highly  statistically  significant  28%  and  30%   reduction   in   the   risk   of   progression   or   death   for   continuous   therapy   versus   MPT   (HR=0.72,   p<0.001)   and   Ld18   (HR=0.70,   p<0.001),   respectively.   There   was   no   significant   PFS   difference   between   giving   lenalidomide   in   cycles   and   MPT.   The   three-­year  PFS  was  42%  for  continuous  Ld  versus  23%  in  the  two  other  arms.    All   subgroups  in  the  continuous  therapy  arm  showed  improved  PFS,  except  for  high-­risk   cytogenetics  patients.     As   for   the   secondary   endpoints,   the   median   TTP   was   significantly   longer   with   continuous  Ld  (32.5  months)  than  with  MPT  (23.9  months;;  p<0.001)  or  Ld18  (21.9   months;;   p<0.001).   Similarly,   2nd   AMT   was   longer   for   continuous   therapy   (39.1   months)  than  for  Ld18  (28.5  months;;  p<0.001)  or  MPT  (26.7  months;;  p<0.001).  Time   to  treatment  failure  (due  to  death,  disease  progression,  toxicity  or  other  reasons)  was   16.9  months  with  continuous  Ld  versus  14.1  months  (p<0.001)  with  MPT  and  17.2   months   (p<0.01)   with   Ld18;;   there   was   no   statistically   significant   TTF   difference   between  Ld18  and  MPT  (17.2  vs.  14.1  months;;  p=0.45973).    

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