Anita DSouza MD MS Froedtert amp MCW Cancer Center Milwaukee WI Objectives Types of amyloidosis How does amyloidosis form Why does myeloma sometimes make amyloid Treatment of amyloidosis ID: 997769
Download Presentation The PPT/PDF document "Amyloidosis- What does it have to do wit..." is the property of its rightful owner. Permission is granted to download and print the materials on this web site for personal, non-commercial use only, and to display it on your personal computer provided you do not modify the materials and that you retain all copyright notices contained in the materials. By downloading content from our website, you accept the terms of this agreement.
1. Amyloidosis- What does it have to do with Myeloma?Anita D’Souza, MD, MSFroedtert & MCW Cancer CenterMilwaukee, WI
2. ObjectivesTypes of amyloidosisHow does amyloidosis form?Why does myeloma sometimes make amyloid?Treatment of amyloidosisResearch- new treatments on the horizon
3. What is amyloidosis?Disorder in which a protein-like material builds up in organsNot degradedSymptoms depend on organ where amyloid builds upSeveral types of amyloidosis, according to the protein of origin
4. “Common” types of systemic amyloidosisAL/Light chain- most common, ~65%ATTRWild type (age-related)Hereditary/familialOther hereditary typesSecondary (AA)
5. Bone marrowplasma cell cloneclonal free light chainsmisfoldedlight chains(AL)organ AL deposition leading to dysfunctionAL AmyloidosisMyeloma>10% plasma cellsBones, Kidneys, Anemia, High calcium
6. Diagnosis- patient and caregiver experienceLousada, I et al. Adv Ther 2015
7. Suspecting amyloidosis in the diagnosisMultisystem diseaseFatigueSwelling in legs, around eyesFrothy urineDizziness with activityBig tongueEnlarged liverPeriorbital bruising
8. DiagnosisTissue diagnosisFat pad and bone marrowInvolved organSubtype amyloid depositsCritical step before starting treatment Mass spectrometry
9. PrognosisStage of diseaseDifference in free light chainsNT proBNPTroponin TBlood pressureRenal failureFunctional statusPlasma cell clone
10. Symptoms/Signs- Heart Amyloid in heartStiff heartHeart failureRhythm problemsSymptoms, SignsFatigueShortness of breathSwellingUnable to lie down (from shortness of breath)Wake up gasping for breathCough, often at nightTestsEchoMRIPYP scanBlood tests (troponin, NTproBNP)
11. Symptoms/Signs- KidneyAmyloid in kidneysNephrotic syndromeKidney failureSymptoms, SignsSwelling in legsPuffiness around the eyesFrothy urineTestsUrine tests (24 h urine protein, urine protein/creatinine ratioLow albuminHigh cholesterol
12. Symptoms/Signs- NeuropathyPeripheral neuropathyAscending numbnessMuscle weaknessGaitMuscle atrophyAutonomic neuropathyDry eyes, mouthAltered sweatingDizziness Diarrhea/ constipationBladder dysfunctionErectile dysfunctionCarpal tunnel Syndrome
13. Amyloid Treatment StrategiesPrevent protein misfoldingSuppress amyloidogenic protein productionDestabilize amyloid deposits
14. Bone marrowplasma cell cloneclonal free light chainsmisfoldedlight chains(AL)organ AL deposition leading to dysfunctionEffective Chemotherapy availableNeeds time for endogenous clearanceChemotherapy can worsen e.g. fluid retention, cardiotoxicity, neuropathyNeed for clinical trials with fibril-directed therapies
15. TreatmentsIMiDsProteasome inhibitorsAlkylatorsSteroidsAntibodiesFibril therapiesThalidomide(Thalomid)Bortezomib (Velcade)Melphalan (Alkeran EvomelaTransplant)Dexamethasone (Decadron)Daratumumab (Darzalex)DoxycyclineLenalidomide (Revlimid)Ixazomib (Ninlaro)Cyclophosphamide (Cytoxan)PrednisoneIsatuximabAnti-SAP abPomalidomide (Pomalyst)Carfilzomib (Kyprolis)Bendamustine (Treanda)CAEL-101OprozomibGreen teaMarizomibNEOD-001
16. Anti-CD38 antibody: Daratumumab
17. Autologous stem cell transplantLong standing responses and excellent outcomes from single centersClinical trial showed high transplant-related mortality, 24%Jaccard, et al. NEJM 2007;357:1083
18. “Real-world” US/Canada data, N=1536D’Souza, A et al. J Clin Oncol 2015
19. To transplant or not to transplant?Patient selection is criticalNT proBNP >5000, TnT >0.06Center experience also keyCenters ≥ 4 AL transplants/yearInduction treatment pre-transplant?CyBorD can convert transplant ineligible to eligibleMay test ability of patients to tolerate treatmentBMPC >10%Gertz, et al. BMT 2013; 48:557D’Souza, et al. JCO 2015; 33:3741Hwa, et al. AJH 2016;91:984
20. Supportive Care-heartLow salt dietDiuretics for swelling Individualized treatment (beta blockers, ACE-inhibitors, anti-arrhythmic)Blood thinners
21. Supportive care-kidneysDiureticsAlbumin infusionsACE-InhibitorsAvoid nephrotoxic medications (pain medications like ibuprofen)
22. Supportive care-neuropathyTopical medicationLidoderm patch, Anesthetic cream, CapsacinNeurotropic medicationsLyrica, NeurontinCymbalta, ElavilPain medications Anti-inflammatory (aspirin, NSAIDs)Narcotics (patch or extended release)
23. Supportive care- autonomic dysfunctionDry eyes and mouth- tear and saliva supplementsLightheadedness when standing- midodrineDiarrhea- Lomotil, loperamide, tincture opiumConstipation- stool softenersBladder dysfunctionErectile dysfunction
24. Foot care- if you can’t feel your feet, you can’t feel cuts or soresFoot care tipsLook between and under your toes every dayWear soft, well-fitting shoesDo not walk barefoot, particularly outsideKeep feet soft and well moisturizedHave nails filed rather than cut A podiatrist can help
25. Carpal tunnel syndromeErgonomic adjustmentWrist braceLocal steroid injectionSurgery
26. Supplements?Multivitamin supplementEGCG (green tea)Curcumin- interesting data in lab, no data in humans except case reports, ?doseKnown neurotoxinsCut down on alcohol (directly toxic to nerves)Stop smoking (damages blood vessels)
27. Doxycycline- old antibioticForloni, G, et al. FEBS Letter 2001 Ward, J, et al. Blood 2011
28. Retrospective clinical dataKumar, S et al. ASH 2012Survival advantage for AL patients who received doxycycline prophylaxis after transplant.Case (N=16)- Control (N=22)Advanced AL: Stage 3 (N=3)/Stage 4 (N=35)Treated with chemotherapyLowered mortality with doxycyclineWechalekar, A et al. ASH 2014, ASH 2015
29. “Fibril-directed therapies”Monoclonal antibodies targeting amyloid fibrilsCAEL101
30. FDA-approved therapies in AmyloidosisIn 2018, patisiran and inotersen (a gene silencer) were approved to treat hereditary transthyretin amyloidosis with neuropathyIn 2019, tafamidis was approved to treated age-related transthyretin amyloidosis of heartVery exciting times in amyloidosis. Note- these drugs don’t work in AL amyloidosis
31. Froedtert & Medical College of Wisconsin Cancer Centerandsouza@mcw.edu@adsouza_mdAmyloidosis Support Groups