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CPC vignettes – challenging cases in the elderly

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

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CPC vignettes – challenging cases in the elderly

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  1. CPC vignettes – challenging cases in the elderly • Consultant Haematologist • University College London Hospital • & North Middlesex University Hospital • Dr Neil Rabin

  2. 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.

  3. Case 1: William How would you treat him ? • 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

  4. Case 1: WilliamDecision – what treatment now? • Continue CTD to maximal response • Switch to salvage treatment (Velcade based) • Proceed to ASCT • Other

  5. Case 1: William CVD CDT M200 THALIDOMIDE Retro-orbital Plasmacytoma Serum paraprotein (g/L) Time (months)

  6. Myeloma IX: AGE DISTRIBUTION BY PATHWAY 150 120 INTENSIVE NON-INTENSIVE 90 NUMBER OF PATIENTS 60 30 40 50 60 70 80 90 AGE Stratification of treatment by age ASCT-eligible Not eligible ? 67.4% of patients entered into Intensive arm proceeded to ASCT

  7. 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

  8. Transplantation in the elderly • ASCT performed at UCLH from 1993 →2010 • 338 patients • Median age 57 years (range 34-71) • 40 patients >65 years Maciocioa P, unpublished data

  9. IFM 99-06 trial • MPT vs MP vs M100 • Age 65-75 • Improvement in PFS/OS with MPT vs MP/M100 Facon T. et al. Lancet; 370:1209-1218, 2007

  10. 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

  11. 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

  12. Case 2: JenniferDecision – what initial treatment? • Aim for induction treatment prior to ASCT • MPV • CTDa or MPT • Clinical trial

  13. 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 1 • 3,274 mg/l pre-cycle 2 • SFLC normal from cycle 4 onward • “Velcade eyes” cycle 6

  14. VISTA study: VMP vs MP VMP Cycles 1-4 Bortezomib 1.3 mg/m2 IV: days 1,4,8,11,22,25,29,32 Melphalan 9 mg/m2 and Prednisone 60 mg/m2 days 1-4 Cycles 5-9 Bortezomib 1.3 mg/m2 IV: days 1,8,22,29 Melphalan 9 mg/m2 and Prednisone 60 mg/m2 days 1-4 R A N D O M I Z E 9 x 6-week cycles (54 weeks) in both arms MP Cycles 1-9 Melphalan 9 mg/m2 and Prednisone 60 mg/m2 days 1-4 • Primary Endpoint: TTP • Secondary Endpoints: CR rate, ORR, TTR, DOR, PFS, TNT, OS, QoL (PRO) San Miguel et al. N Engl J Med 2008;359:906–17

  15. VISTA: Updated Survival 13.3 months OS benefit San Miguel J F et al. JCO 2013

  16. 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

  17. Treatment Options • Intensive: not fit • Non-Intensive • Clinical Trial: ineligible • NICE approved: • CTDa • MPT • VMP (if unable to receive thalidomide based regimen) • Others: • M&P • Cyclo Dex Case 3

  18. 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)

  19. Case 3: RuthDecision – what treatment now? • Velcade re-treatment • Bendamustine • Clinical trial • Other

  20. Overview: Case [t(4;14)] 2008 - 2012 NICE approved Clinical Trials 1st Line 1st Line 2nd Line 3rd Line 4th Line 5th Line 6th Line

  21. Case 4: John • 76 year old Afro-Caribbean retired builder • 6 month history of exertionaldyspnoea 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

  22. Case 4: JohnDecision – what is the likely diagnosis? • Symptomatic myeloma • AL cardiac amyloidosis • Cardiac failure (unrelated) • Other

  23. Case 4: John • Referred to National Amyloidosis Centre • Echocardiogram characteristic of amyloid • IVSd1.9 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

  24. Case 4: John • Endocardial biopsy • stained with Congo Red • Endocardial biopsy • showing apple-green birefringence • in polarised light Lydia Lee et al, BJHM, Nov 2011 • Positive immunohistochemical • staining for transthyretin

  25. 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

  26. 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)

  27. Hereditary cardiac amyloid (TTR) 4 % Afro-Caribbeans Val122Ile Variable penetrance Presents in the 7th decade Cardiac failure / arrythmia Resistant to diuretics / ACE i Diagnosis based on -Finding of cardiac amyloid -Mutation in TTR gene Occasionally cardiac biopsy Gilmore et al, Heart 1999

  28. 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

  29. Case 5: JoanDecision – how would you treat? • Observation only • Treatment for anaemia alone • Systemic chemotherapy • Other

  30. 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 months • Asymptomatic • 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

  31. Case 5: Joan How would you treat her ?

  32. Case 5: JoanDecision – how would you treat her? • Systemic chemotherapy + Analgesia • Systemic chemotherapy + Radiotherapy • Systemic chemotherapy + Vertebral augmentation • Other

  33. 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

  34. Case 5: Joan VelcadeDex CycloDex Weekly sc, Velcade Dose reduced to 1 mg/m2 from cycle 3 Completed 8 cycles No sig. Rx toxicity Progressed within 3 months completing Velcade RT K’plasty

  35. 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

  36. 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

  37. Case 6: ArthurDecision – how would you treat? • Analgesia + Bisphosphonate treatment • + Radiotherapy • + Dexamethasone • + Systemic chemotherapy

  38. 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

  39. 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) • Velcadesc 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

  40. 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

  41. PALUMBO ET AL< BLOOD, 27 OCTOBER 2011 VOLUME 118, NUMBER 17

  42. 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

  43. UCLH • Clinical team • Kwee Yong / Shirley D’Sa / Ali Rismani / RakeshPopat • Jaimal Kothari / Dean Smith / Laura Percy / Lydia Lee • Clinical Nurse Specialists • Aviva Cerner / Samantha Darby • Jude Dorman • Clinical Trials • Janet Lyons – Lewis / Diane Gowers • North Middlesex • Clinical Nurse Specialist • Millicent Blake – McCoy • Clinical Trials • Christy Griffin-Pritchard

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