Myeloma(Clinical(Presenta1on( (the(need(for(a(changing(paradigm? ( - PowerPoint PPT Presentation

Myeloma(Clinical(Presenta1on( –(the(need(for(a(changing(paradigm? ( Professor'Gordon'Cook' St'James’s'Ins4tute'of'Oncology ' Leeds'Teaching'Hospital '

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, 481 2 NCI, SEER database

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).' I II III 50 40 %patients 30 20 10 0 <40 40-49 50-59 60-69 70-79 >80 Age, yrs Ludwig et al, J Clin Oncol, 2010, 28(9), 1599

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'92:2413245,'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:' '

Survival(&(years(of(life(lost ( Ludwig et al, J Clin Oncol, 2010, 28(9), 1599

Survival(&(years(of(life(lost ( Average Years life lost 45 All Male Female 40 35 30 25 20 15 10 5 0 <40 40-49 50-59 60-69 70-79 >80 Age Ludwig et al, J Clin Oncol, 2010, 28(9), 1599

Survivorship(–(CCT(vs(ASCT ( Years of Life lost 40 36.8 35.9 35 CCT ASCT 30 27.4 25.6 25 21 18.2 20 13.6 13.1 15 10.6 8.1 10 5 0 <40 40-49 50-59 60-69 70-79 Ludwig et al, J Clin Oncol, 2010, 28(9), 1599

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, 747-751

• ≈ 40% presented with late stage disease, pre- & post- screening. • ≈ 20% experienced symptoms >3 msn pre-diagnosis ' 60 90 50 80 %De Novo Patients %pateitns with co- 70 40 morbidities 60 50 30 40 20 30 20 10 10 0 0 MBD No MBD Flanagan et al, Post Grad Med J, 1988, 64, 747-751

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, 635-40

Symptoms,(stage(and(delay(in(diagnosis ( 60 80 I II III Symptoms at presentation 70 50 60 40 %patients 50 40 30 30 20 20 10 10 0 0 <3/12 3/12 - 6/12 >6/12 First symptom to Diagnosis (mns) Kariyawasan et al, QJ Med, 2007, 100, 635-40

Kariyawasan)et)al,)QJ)Med,)2007,)100,)635940 )

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.'

New(Diagnosis(of(PCD((Aug’11PJuly’12) ( 70 OP IP 60 %New DIagnosis 50 40 30 20 10 0 Plasmacyt Asympt Sympt

New(Diagnosis(through(emergency:( ( Cause(of(Admission ( Confusion EM disease HyperCal SCC Bone Pain AKI 0 5 10 15 20 25 30 35 40 %Acute admissions (Newly Diagnosed)

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%)'

New(diagnosis(&(OS ( OS - IP vs OP IP Diagn 100 OP Diagn Percent survival 50 p=0.02 HR 3.66 (95% CI 1.24, 11.65) 0 0 200 400 600 Days elapsed Median Survival: I/P 14.8 mns O/P NR

Na1onal(Cancer(Pa1ent(Experience(survey ( >3 pre-referral consultations % Adj ORs 95% CI MM 50.6 3.42 3.01, 3.9 HD 42.2 1.67 1.34, 2.08 NHL 32.2 1.5 1.5, 1.69 Leukaemia 27.6 1.15 0.99, 1.32 Lyratzopoulos et a, Lancet Oncology, 2012, 13, 353

Effects(of(ethnicity(and(age ( Lyratzopoulos et a, Lancet Oncology, 2012, 13, 353

Late/delayed(Diagnosis ( Solu4ons? '

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?

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

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

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

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

Early(vs(Deferred/delayed( treatment (

Early( vs (Deferred(Treatment(in(early(MM ( Mortality Progression Wheatley et al, Cochrane Database Syst Rev, 2003 (1) pp. CD004023

Early( vs (Deferred(Treatment(in(early(MM ( Vertebral Compression Fractures Leukaemic Transformation

Trea1ng(early(disease ( • IMiDs' – Witzig'et'al' (Leukaemia,'doi'10.1038/leu.2012.236) 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.'

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

Thank you!