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

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

Jan 21, 2024 6 likes •322 views

Myeloma(Clinical(Presenta1on( (the(need(for(a(changing(paradigm? ( Professor'Gordon'Cook' St'Jamess'Ins4tute'of'Oncology ' Leeds'Teaching'Hospital ' Multiple Myeloma 28,700 & 19,920 new diagnoses p.a. in the EU 1 & USA 2 ,

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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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Multiple Myeloma

  • 28,700 & 19,920 new diagnoses p.a. in the EU1 & USA2,

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)

1Boyle et al, Ann Oncol, 2005, 16, 481 2NCI, SEER database

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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).'

Ludwig et al, J Clin Oncol, 2010, 28(9), 1599

10 20 30 40 50 <40 40-49 50-59 60-69 70-79 >80 %patients Age, yrs I II III

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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:'

'

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Survival(&(years(of(life(lost (

Ludwig et al, J Clin Oncol, 2010, 28(9), 1599

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Survival(&(years(of(life(lost (

Ludwig et al, J Clin Oncol, 2010, 28(9), 1599

5 10 15 20 25 30 35 40 45 <40 40-49 50-59 60-69 70-79 >80 All Male Female

Average Years life lost Age

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Survivorship(–(CCT(vs(ASCT (

Ludwig et al, J Clin Oncol, 2010, 28(9), 1599 Years of Life lost

36.8 27.4 21 13.6 8.1 35.9 25.6 18.2 13.1 10.6

5 10 15 20 25 30 35 40 <40 40-49 50-59 60-69 70-79 CCT ASCT

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Early(diagnosis(&(screening (

Flanagan et al, Post Grad Med J, 1988, 64, 747-751

  • 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.''

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10 20 30 40 50 60 %De Novo Patients Flanagan et al, Post Grad Med J, 1988, 64, 747-751 10 20 30 40 50 60 70 80 90 MBD No MBD %pateitns with co- morbidities

  • ≈40% presented with late stage disease, pre- & post-

screening.

  • ≈20% experienced symptoms >3 msn pre-diagnosis'
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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

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Symptoms,(stage(and(delay(in(diagnosis (

10 20 30 40 50 60 70 80

Symptoms at presentation 10 20 30 40 50 60 <3/12 3/12 - 6/12 >6/12 %patients First symptom to Diagnosis (mns) I II III

Kariyawasan et al, QJ Med, 2007, 100, 635-40

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

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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.'

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New(Diagnosis(of(PCD((Aug’11PJuly’12) (

10 20 30 40 50 60 70 Plasmacyt Asympt Sympt %New DIagnosis

OP IP

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New(Diagnosis(through(emergency:( ( Cause(of(Admission (

5 10 15 20 25 30 35 40 AKI Bone Pain SCC HyperCal EM disease Confusion %Acute admissions (Newly Diagnosed)

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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%)'

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OS - IP vs OP

Days elapsed Percent survival

200 400 600 50 100

IP Diagn OP Diagn

New(diagnosis(&(OS (

Median Survival: I/P 14.8 mns O/P NR p=0.02 HR 3.66 (95% CI 1.24, 11.65)

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Na1onal(Cancer(Pa1ent(Experience(survey (

Lyratzopoulos et a, Lancet Oncology, 2012, 13, 353 % 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 >3 pre-referral consultations

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Effects(of(ethnicity(and(age (

Lyratzopoulos et a, Lancet Oncology, 2012, 13, 353

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Late/delayed(Diagnosis (

Solu4ons? '

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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?
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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

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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

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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

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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

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Early(vs(Deferred/delayed( treatment (

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Early(vs(Deferred(Treatment(in(early(MM (

Wheatley et al, Cochrane Database Syst Rev, 2003 (1) pp. CD004023

Mortality Progression

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Early(vs(Deferred(Treatment(in(early(MM (

Vertebral Compression Fractures Leukaemic Transformation

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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.'

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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

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Thank you!