cpc vignettes – challenging cases in the elderly
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CPC vignettes – challenging cases in the elderly. Consultant Haematologist University College London Hospital & North Middlesex University Hospital. Dr Neil Rabin. Case 1: William. 70 year old retired biomedical scientist June 2007: weight loss and fatigue - PowerPoint PPT PresentationTRANSCRIPT
CPC vignettes – challenging cases in the elderly
Consultant HaematologistUniversity College London Hospital& North Middlesex University Hospital
Dr Neil Rabin
Case 1: William• 70 year old retired biomedical scientist• June 2007: weight loss and fatigue• IgG lambda pp 44g/L, BJP negative• Hypercalcaemia with normal renal function• BM 80-90% plasma cells • SS: multiple lytic lesions• Cytogenetic – FISH - normal• ISS stage: 2
• PMHx – Asthma, investigated for SVTs• PHx - Ex smoker. PS = 0. Active lifestyle.
Case 1: William• Diagnosed with symptomatic myeloma (age 70)
• Treated with Cyclophosphamide Dexamethasone Thalidomide (CTD) for 4 months at local hospital
• PP falls from 44g/L to 13 g/L (partial response)
• Echocardiogram – normal• Creatinine clearance – normal
How would you treat him ?
Case 1: WilliamDecision – what treatment now?
• Continue CTD to maximal response• Switch to salvage treatment (Velcade based)• Proceed to ASCT• Other
Case 1: WilliamM200 THALIDOMIDE CVDCDT
- 10 20 30 40 50 60 70 80 90 100 -
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Time (months)
Ser
um p
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Retro-orbitalPlasmacytoma
Stratification of treatment by age
40 50 60 70 80 90
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AGE
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Myeloma IX: AGE DISTRIBUTION BY PATHWAY
INTENSIVE NON-INTENSIVE
ASCT-eligible Not eligible
?
67.4% of patients entered into Intensive arm proceeded to ASCT
How do we decide if a patient is for intensive therapy (ASCT eligible) ?• ?
• Age• Performance status• Organ Function• Disease biology• Adequate stem cells• Patient choice
Transplantation in the elderly
Maciocioa P, unpublished data
• ASCT performed at UCLH from 1993 →2010• 338 patients• Median age 57 years (range 34-71)• 40 patients >65 years
Facon T. et al. Lancet; 370:1209-1218, 2007
• IFM 99-06 trial
• MPT vs MP vs M100• Age 65-75
• Improvement in PFS/OS with MPT vs MP/M100
Case 2: Jennifer• 69 year old retired elderly care nurse• Anaemia last 2 years• PMHx -↑BP• Fall going down the stairs at home• PHx – previously active, current PS = 2
Case 2: Jennifer• CT fracture through lytic lesion with extraosseous tumour• Biopsy lytic lesion = plasma cell neoplasm• MRI: multiple lytic lesions vertebrae, sacrum, femora,
fractures T6, L1, L5, small paravertebral mass at T6• Haemoglobin 9 g/dL, Creatinine 107 umol/L, Calcium
normal• IgD lambda PP 12 g/L + Lambda LC• Urinary BJP 2.72 g/L• BM 80-90% plasma cells • ISS stage 3 (beta-2 m 7.7mg/L)• Cytogenetic – FISH failed
Case 2: JenniferDecision – what initial treatment?
• Aim for induction treatment prior to ASCT• MPV• CTDa or MPT• Clinical trial
Case 2: Jennifer• Decision for non-intensive treatment• Declined clinical trial entry• Treated with MPV November 2012• Intra-medullary nail inserted November 2012• Single fraction radiotherapy to humerus• Completed 8 cycles – achieving CR• Lambda LC
15,571 mg/l pre-cycle 13,274 mg/l pre-cycle 2SFLC normal from cycle 4 onward“Velcade eyes” cycle 6
San Miguel et al. N Engl J Med 2008;359:906–17
VMPCycles 1-4Bortezomib 1.3 mg/m2 IV: days 1,4,8,11,22,25,29,32Melphalan 9 mg/m2 and Prednisone 60 mg/m2 days 1-4
Cycles 5-9Bortezomib 1.3 mg/m2 IV: days 1,8,22,29Melphalan 9 mg/m2 and Prednisone 60 mg/m2 days 1-4
MPCycles 1-9Melphalan 9 mg/m2 and Prednisone 60 mg/m2 days 1-4
RANDOMIZE
9 x 6-week cycles (54 weeks) in both arms
Primary Endpoint: TTP Secondary Endpoints: CR rate, ORR, TTR, DOR, PFS, TNT, OS, QoL
(PRO)
VISTA study: VMP vs MP
VISTA: Updated Survival
San Miguel J F et al. JCO 2013
13.3 months OS benefit
Case 3: Ruth• 68 year old retired secretary• PMHx – 2005: invasive ductal breast ca – treated with
lumpectomy, RT, tamoxifem / arimidex• 2008: Anaemia, Back pain, Epistaxis• IgG lambda PP 82 g/L, BJP 0.74g/L• BM 80% plasma cells • SS: multiple lytic lesions• Cytogenetic – FISH – t(4:14)• ISS stage: 2
Treatment Options
1. Intensive: not fit2. Non-Intensive
a) Clinical Trial: ineligibleb) NICE approved:
1. CTDa2. MPT3. VMP (if unable to receive thalidomide based regimen)
c) Others:1. M&P2. Cyclo Dex
Case 3
Case 3: Ruth• MPT x 3
– Bowel disturbance, neutropaenia– MR (PP 82 → 56 g/L)
• VMP x 8– Biweekly to weekly bortezomib– Weekly bortezomib at 1.3 mg/m2→ 1mg/m2
(progressive PN)– VGPR (PP 56 → 4 g/L)
• Relapsed 2 years later (2010):• Lenalidomide and Dex x 4
– PD on treatment (pp 36 → 65 g/L)
Case 3: RuthDecision – what treatment now?
• Velcade re-treatment• Bendamustine• Clinical trial• Other
Overview: Case [t(4;14)] 2008 - 2012
MPT VMP RD Velcade & Panobinostat MUK 1 ADMYRE FOCUS
1st Line 3rd Line 4th Line 5th Line1st Line 2nd Line 6th Line
NICE approved Clinical Trials
1 1 1 2 3 3 3 4 4 50
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Treatment Line
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Case 4: John• 76 year old Afro-Caribbean retired builder• 6 month history of exertional dyspnoea and marked
peripheral oedema• Repeat admissions to hospital• PMHx – Diabetes / ↑BP / ↑Cholesterol / Atrial fibrillation• Echocardiogram – 30% LVEF, severe concentric LVH• Lambda LC noted in serum and urine
– Kappa FLC 11 mg/L, lambda FLC 864 mg/L– Haemoglobin / Creatinine / Calcium - normal
• Bone marrow – 75% plasma cells• Skeletal survey normal
Case 4: JohnDecision – what is the likely diagnosis?
• Symptomatic myeloma• AL cardiac amyloidosis• Cardiac failure (unrelated)• Other
Case 4: John• Referred to National Amyloidosis Centre
– Echocardiogram characteristic of amyloidIVSd 1.9 cm, moderate to severely impaired LV systolic function, grade 2 diastolic dysfunction.
– ECG showed atrial flutter, variable AV block,↓ QRS– Troponin-t 0.1 ng/mL (normal), NT pro BNP 430 pmol/L– No visceral amyloid detected on SAP scintography
• Differential diagnosis of– AL amyloid– Senile cardiac amyloid with co-existent myeloma– Hereditary cardiac amyloid with co-existent myeloma
Case 4: John
Endocardial biopsystained with Congo Red
Endocardial biopsyshowing apple-green birefringencein polarised light
Positive immunohistochemicalstaining for transthyretin
Lydia Lee et al, BJHM, Nov 2011
Case 4: John• Hereditary cardiac amyloid (TTR variant)
– Reviewed regularly at the NAC and local cardiologist– Cardiac medication (Enalapril, Digoxin and
Furosemide) adjusted. Anti-coagulated for mural thrombus
– Cardiac function remained stable for 2 years (NYHA II)– Treatment – low salt diet, fluid management, diuretics
• Myeloma– Declined chemotherapy (? initial treatment needed)– Inappropriate to treat for AL cardiac amyloid
• Died 2 years later
Cardiac amyloid• Deposition of amyloid fibrils (cardiac and other tissues)• Common findings
– Low amplitude QRS complexes (<1mV in pre-cordial leads or <0.5mV in all limb leads)
– Pseudoinfarction pattern (Q waves in consecutive leads)
– Conduction delays + arrhythmias (commonly AF)– LV wall thickening in the absence of hypertension
• AL amyloid (associated with a plasma cell clone)• Senile systemic amyloid (wild type transthyretin)• Hereditary cardiac amyloid (ATTR)
Hereditary cardiac amyloid (TTR)
4 % Afro-Caribbeans Val122IleVariable penetrancePresents in the 7th decadeCardiac failure / arrythmiaResistant to diuretics / ACE i
Diagnosis based on-Finding of cardiac amyloid-Mutation in TTR geneOccasionally cardiac biopsy
Gilmore et al, Heart 1999
Case 5: Joan• 86 year old artist• Referred to general haematology clinic with normocytic
anaemia (Hb 9.8 g/dL) developed previous 2 years• Symptom - fatigue, and exertional chest pain• IgG kappa PP 16 g/L, no BJP, normal SFLC ratio• Creatinine, Calcium - normal• BM 20% plasma cells • SS: no lytic lesions• Cytogenetic – FISH – 1q gain• ISS stage: 1• PMHx - ↑BP, Hiatus hernia, previous Cystitis• PHx - Lives alone, independent with ADL
Case 5: JoanDecision – how would you treat?
• Observation only• Treatment for anaemia alone• Systemic chemotherapy• Other
Case 5: Joan• Adopted watchful waiting
– Reviewed by cardiologist – normal myocardial perfusion scan
– Erythropoetin, rise in haemaglobin → 11 g/L– Bisphosphonates (absence of bone disease)
• Observed for 9 monthsAsymptomatic
• Presented with acute lower back pain– Lower back pain whilst gardening– Plain x-rays showed fractures T12, L4 and L5– Paraprotein increase from 16g/L → 24 g/L
Case 5: Joan
How would you treat her ?
Case 5: JoanDecision – how would you treat her?
• Systemic chemotherapy + Analgesia• Systemic chemotherapy + Radiotherapy• Systemic chemotherapy + Vertebral augmentation• Other
Case 5:Joan• Admitted for pain control
– Treated with long acting and short acting opiate analgesia
– Received palliative RT to lumbar spine (8Gy)– Started on Cyclophosphamide po weekly, and
Dexamethasone 20mg daily for 4 days / month• Discharged when mobility improved• Ongoing problems with pain
– Multiple level kyphoplasty at Royal National Orthopaedic Hospital (Sean Molloy)
– Very good symptomatic benefit– Support from palliative care team, and liaison with
primary care
Case 5: Joan Velcade Dex
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RT K’plastyWeekly sc, VelcadeDose reduced to 1 mg/m2 from cycle 3Completed 8 cyclesNo sig. Rx toxicity
Progressed within 3 monthscompleting Velcade
Case 6: Arthur• 97 year old • Known diagnosis of Alzheimer’s disease
– Mobile with a Zimmer Frame– Lives at home with carers – washing/cooking/cleaning– Memantadine.
• PMHx - ↑BP, GORD, BPH• 2012: 6 week history
– Confusion– Lower back pain– Bed bound
Case 6: Arthur• IgG kappa pp 14g/L, BJP – faint band • Haemoglobin 11 g/dL• Hypercalcaemia• Creatinine 120 umol/L (eGFR 50 ml/min)• BM 40% plasma cells • SS: Fracture L4/L5, lytic lesion pelvis/femur • Cytogenetic – FISH – 17p del• ISS stage: 2• Diagnosed with symptomatic myeloma
Case 6: ArthurDecision – how would you treat?
• Analgesia + Bisphosphonate treatment• + Radiotherapy• + Dexamethasone• + Systemic chemotherapy
Case 6: Arthur• Pain control
– Palliative care input– Opiate analgesia
• Treatment– Dexamethasone (low dose). Decision not systemic RX
– Bisphophonate– Radiotherapy to lumbar spine and left ilium
• Discharged home, returned to previous baseline– Re-instituted package of care– Community palliative care input– Haematology day unit
Case 6: Arthur• Well for 3 months• Decline mobility
– Pain weight bearing right leg. Unable to mobilise• Re-assessed
– Radiotherapy – right femur + sacrum (symptom better)– Systemic chemotherapy
• ? Imid based (need for anticoagulation)• ? Proteosome inhibitor (able to visit hospital)
– Velcade sc weekly at 1mg/m2, with Dex (10mg 2/7)• PP 14 → < 3g/L (VGPR). Received 4 cycles, stop.• No treatment emergent problems
• Stable for 9 months → RIP
Frail elderly patient• Dependent on co-morbidities – more likely > 75 yrs.• Assessments of frailty / co-morbidities
– Comprehensive geriatric assessment (CGA)– Cumulative illness rating scale (CIRS-G)
• Important to note the impact of disease on performance status
• Ability to benefit from novel agents• Modification of treatment dose and schedule• Balance goal of depth of response with minimising
toxicities
PALUMBO ET AL< BLOOD, 27 OCTOBER 2011 VOLUME 118, NUMBER 17
Summary• Fit elderly should be treated as any other patient• Dependent on co-morbidities – more likely > 75 yrs.• Assessments of frailty / co-morbidities • Important to note the impact of disease on performance
status• Ability to benefit from novel agents• Modification of treatment dose and schedule• Balance goal of depth of response with minimising
toxicities• Consider other causes for co-existent medical problems
UCLH• Clinical team
Kwee Yong / Shirley D’Sa / Ali Rismani / Rakesh PopatJaimal Kothari / Dean Smith / Laura Percy / Lydia Lee
• Clinical Nurse SpecialistsAviva Cerner / Samantha DarbyJude Dorman
• Clinical TrialsJanet Lyons – Lewis / Diane Gowers
North Middlesex• Clinical Nurse Specialist
Millicent Blake – McCoy• Clinical Trials
Christy Griffin-Pritchard