Myeloma(Clinical(Presenta1on( (the(need(for(a(changing(paradigm?( Professor'Gordon'Cook' St'James s'ins4tute'of'oncology' Leeds'Teaching'Hospital'
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1 Myeloma(Clinical(Presenta1on( (the(need(for(a(changing(paradigm?( Professor'Gordon'Cook' St'James s'ins4tute'of'oncology' Leeds'Teaching'Hospital'
2 Multiple Myeloma 28,700 & 19,920 new diagnoses p.a. in the EU 1 & USA 2, respectively 4,000 new patients p.a & 3,000 deaths p.a. in the UK Recent improvement in survival as a result of new treatments but access to optimum treatment and managing expectations are big challenges 37% are diagnosed through emergency routes rather than referral by GPs. This compares to an average 23% across all cancer types (National Cancer Intelligence Network 2012) Patients diagnosed through emergency routes have significantly poorer one-year survival outcomes compared to those diagnosed by GP referral (51% vs. 82%) (National Cancer Intelligence Network 2012) 1 Boyle et al, Ann Oncol, 2005, 16, NCI, SEER database
3 Survival(&(years(of(life(lost( N=10,'549'from'17'centres'in'EU/USA/Japan'with'a' med'fu'3.25'&'70.3%'derived'from'studies.' Correla4on'with'increasing'age'and'advanced'stage' at'presenta4on'(r=0.13,'95%ci'0.11,'0.16).' %patients I II III < >80 Age, yrs Ludwig et al, J Clin Oncol, 2010, 28(9), 1599
4 Rela1ve(Excess(Risk( Median'years'of'life'lost'was'16.8'years'(n=10,549)'' Significantly'higher'than'the'12.5'years'for'all'cancers'(Burnet' et'al,'br'j'cancer'92: ,'2005)' US'Na4onal'Center'of'Health'Sta4s4cs:'median'14.0'years'of' life'lost'for'mm'myeloma'(2004)' Bri4sh'Columbia'Cancer'Registry:'median'12.7'years'of'life' lost'for'mm'(2007).'' East'Anglia,'UK:'median'10.3'years'of'life'lost'for'MM' (1990c94)' Rela4ve'excess'risk'(RER)'of'death:' '
5 Survival(&(years(of(life(lost( Ludwig et al, J Clin Oncol, 2010, 28(9), 1599
6 Survival(&(years(of(life(lost( Average Years life lost All Male Female < >80 Age Ludwig et al, J Clin Oncol, 2010, 28(9), 1599
7 Survivorship( (CCT(vs(ASCT( Years of Life lost CCT ASCT < Ludwig et al, J Clin Oncol, 2010, 28(9), 1599
8 Early(diagnosis(&(screening( Early'stage'screening'programme'(1983)'' electrophoresis'of'all'serum'samples'with'globulin'levels'over' 35g/irrespec4ve'of'the'source'of'the'samples'or'the' provisional'diagnosis'and'' marrow'examina4on'and'electrophoresis'at'an'early'stage'in' pa4ents'with'an'unexplained'persistently'raised'esr.' Prior'to'screening,'n=79/60mns,'postcimplementa4on,' n=120/60mns'with'an'expected'figure'of'86.3'(cancer' registra4on'for'england'and'wales'1977c80).' Screening'iden4fied'7'pa4ents'who'died'soon'afer' diagnosis'from'cardiocrespiratory'comorbidi4es'who' would'otherwise'been'missed.'' Flanagan et al, Post Grad Med J, 1988, 64,
9 40% presented with late stage disease, pre- & postscreening. 20% experienced symptoms >3 msn pre-diagnosis' %De Novo Patients %pateitns with comorbidities MBD No MBD Flanagan et al, Post Grad Med J, 1988, 64,
10 Causes(&(consequences(of(late(Diagnosis( Retrospec4ve'audit'of'n=92'De'Novo'pa4ents' 30%'diagnosed'<3'months'from'first'symptom' 55%'ini4ally'presented'to'a'GP,''&'in'56%'of'these' there'was'an'interval'of'>6'months'(>12'months'in' 33%)'before'specialist'referral.'' Delay'of'>6'months'from'first'symptom'to' diagnosis'in'67.4%' Kariyawasan et al, QJ Med, 2007, 100,
11 Symptoms,(stage(and(delay(in(diagnosis( Symptoms at presentation %patients I II III <3/12 3/12-6/12 >6/12 First symptom to Diagnosis (mns) Kariyawasan et al, QJ Med, 2007, 100,
12 Kariyawasan)et)al,)QJ)Med,)2007,)100,)635940)
13 LTH(Myeloma(New(Diagnosis( LTH'is'a'2400cbedded'acute'hospitals'trust'serving' a'secondary'care'popula4on'of'720,000'(2008c09)' &'a'ter4ary'care'popula4on'of'2.7m' August'2011cJuly'2012,'64'new'diagnoses'of'PCD' from'secondary'care'catchment:' 54'Symptoma4c,'9'Asymptoma4c'&'1'Plasmacytoma' 22'of'total'PCD'(34%)'diagnosed'as'a'result'of' admission'but'represents'38%(of'symptoma4c' MM.'
14 New(Diagnosis(of(PCD((Aug 11PJuly 12)( OP IP %New DIagnosis Plasmacyt Asympt Sympt
15 New(Diagnosis(through(emergency:( Cause(of(Admission( Confusion EM disease HyperCal SCC Bone Pain AKI %Acute admissions (Newly Diagnosed)
16 New(Diagnoses(&(OS( Median'FU'8.7'mns'(0.4,'16)'for'all' Diagnosed'IP'Med'FU'10.2'(0.4,'15)' Diagnosed'OP'Med'FU'8.6'(0.8,'18)' 13/54'(24%)'have'died:' Diagnosed'IP'9/21(43%)' Diagnosed'OP''4/33'(12%)'
17 New(diagnosis(&(OS( OS - IP vs OP Percent survival 100 IP Diagn OP Diagn 50 p=0.02 HR 3.66 (95% CI 1.24, 11.65) Days elapsed Median Survival: I/P 14.8 mns O/P NR
18 Na1onal(Cancer(Pa1ent(Experience(survey( >3 pre-referral consultations % Adj ORs 95% CI MM , 3.9 HD , 2.08 NHL , 1.69 Leukaemia , 1.32 Lyratzopoulos et a, Lancet Oncology, 2012, 13, 353
19 Effects(of(ethnicity(and(age( Lyratzopoulos et a, Lancet Oncology, 2012, 13, 353
20 Late/delayed(Diagnosis( Solu4ons?'
21 Late diagnosis: why? Rarity? GPs may only see 2 myeloma patients in their career Lack of GP awareness of myeloma Vague presenting symptoms typical of demographic e.g. lower back pain (osteoporosis), infection and fatigue Late presentation by patients Low public profile No screening?
22 Myeloma UK work on improving early diagnosis A GP education and awareness campaign aimed at reducing the likelihood of delays in diagnosis Launched by Myeloma UK in mid-2010 It engages myeloma patients, their networks and the public in helping GPs recognise the signs and symptoms of myeloma It involves campaigners to TAKE 2 or more Myeloma Diagnosis Pathways to their GPs and encouraging others to do the same
23 The Myeloma Diagnosis Pathway The Myeloma Diagnosis Pathway (MDP) is a simple two-sided algorithmic reference tool for GPs outlining signs, symptoms and tests to take for myeloma It was developed by Myeloma UK with the help of its medical advisory committee and GP reviewers
24 TAKE 2 Campaign: the impact Reached over 9,000 GPs to-date Over 150 MPs supported the campaign Is now being replicated in countries around the world including Australia, The Netherlands, Belgium, USA and Portugal, Canada and China Excellent feedback from GPs via surveys and unsolicited comments Support from Department of Health Long-term impact will be assessed against baseline research
25 NAEDI National Awareness and Early Diagnosis Initiative Early diagnosis, estimated 10,000 deaths per annum could be saved Prevention lifestyle Screening bowel, breast HPV vaccination testing Original focus lung, breast, colorectal, prostate and skin Rarer cancers now a priority but challenging
26 Early(vs(Deferred/delayed( treatment(
27 Early(vs(Deferred(Treatment(in(early(MM( Mortality Progression Wheatley et al, Cochrane Database Syst Rev, 2003 (1) pp. CD004023
28 Early(vs(Deferred(Treatment(in(early(MM( Vertebral Compression Fractures Leukaemic Transformation
29 Trea1ng(early(disease( IMiDs' Witzig'et'al'(Leukaemia,'doi' /leu ) Thalidomide/Zom'vs'Zom'(n=68):'TTP'2.4'yrs'(1.4,'3.6)'vs' 1.2'yrs'(0.7,'2.5),'p=0.02.' Detweiler'et'al'(Am'J'Hemat,'2010,'85,'10,'737),'n=31' treated'with'thal'monotherapy.'ttp'61'mns'>pr,'39mns' MR'&'9mns'<MR' Immunotherapy' An4cKIR'an4body'(IPH2101)'in'clinical'trials' ImMucin'vaccine'trialed'in'RRMM'and'now'asyptoma4c' MM'being'studied.'
30 Summary Improvement in survival with current treatment strategies evident A delayed diagnosis is a significant problem resulting in undue morbidity and health-related QoL issues. Modest investments of time and money in early diagnosis has the potential to improve survival and quality of life Early diagnosis may offer new opportunities for disease management strategies
31 Thank you!
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