issue 7 spring 2015 al amyloidosis matters

Matters

Issue 7 SPRING 2015

AL amyloidosis

News and notes 2

Special feature 3A report on the AL amyloidosis Infoday 2014

Medical matters 4AL amyloidosis and the kidneys

Patient experience 6Mark McConway talks about his experience of AL amyloidosis

AL amyloidosis Patient and Family Infoday videos availableWe are pleased to announce that films of all the presentations from the AL amyloidosis Infoday held on the 5 September 2014 in London are now available to view online.

Myeloma UK holds Patient and Family AL amyloidosis Infodays every yearto bring people affected by the condition together to share experiences,hear about the latest treatments and research direct from experts and tolearn more about the support Myeloma UK provides. These videos from2014 Infoday include:

• Dr Julian Gillmore giving an introduction to AL amyloidosis

• Dr Ashutosh Wechalekar explaining current treatment strategies

• Prof Philip Hawkins outlining future treatment strategies

• Dr Helen Lachmann talking about the management of complicationsof AL amyloidosis and side-effects of treatment

• Dr Marianna Fontana covering cardiac imaging in AL amyloidosis

• Patient Hill Gaston from Cambridge providing a personal account of his experience of AL amyloidosis

The videos are all available on Myeloma TV www.myelomatv.org.uk.Myeloma UK Services Events Co-ordinator Hannah Bingham said, “Peopleaffected by AL amyloidosis get so much from Patient and Family Infodays:apart from having the opportunity to chat with others in a similar situation,up-to-date knowledge from a range of experts is very important whenmaking decisions about treatment and care. We are delighted that peoplewho were not able to attend the event will now have a chance to benefitfrom the expert knowledge shared on the day.”

For a write up of the 2014 Infoday go to page 3.

IN THIS ISSUE

WelcomeWelcome to the latest issue of AL amyloidosis Matters.

In this issue we focus on AL amyloidosis and the kidneys, have our regular news about research and newtreatments in development forAL amyloidosis and a patientexperience by Mark McConway.

We also have a short reportfrom the 2014 AL amyloidosisInfoday, for details of the 2015 Infoday please visitwww.myeloma.org.uk/infodays.

If you have any suggestions for future articles for thenewsletter or would like toprovide a patient experienceplease contact me on 0131 557 3332 or [email protected].

We hope you find this issueinteresting and informative.

Sue PerkinsService Development Manager

AL amyloidosis MattersFor feedback, comments and questions about AL amyloidosis Matterscontact Sue Perkins on 0131 557 3332 or [email protected]

Ixazomib highlighted as a promising new treatment for AL amyloidosisThe US Food and Drug Administration (FDA) has granted ‘breakthroughtherapy designation’ to ixazomib for relapsed and/or refractory ALamyloidosis. Breakthrough therapy designation means that ixazomib will be prioritised and reviewed by the FDA quickly to decide whether itshould be approved for use in the US. In Europe, new treatments must be approved by the European Medicines Agency (EMA) before they canbecome available. However, FDA approval of a treatment normally sets a precedent for it to be approved across Europe. Ixazomib is a type of drug called a proteasome inhibitor, like Velcade® (bortezomib) and Kyprolis®

(carfilzomib) which are used to treat myeloma. Unlike these, ixazomib is an oral (by mouth) proteasome inhibitor and the first treatment for AL amyloidosis to be granted breakthrough therapy status by the FDA.

Latest research in AL amyloidosis featured at ASHThe American Society of Hematology (ASH) 2014 Annual Scientific Meeting,which took place in San Francisco from 6 – 9 December, featured a numberof oral and poster presentations on the latest advances in AL amyloidosis.These included research on the genetic abnormalities associated with AL amyloidosis which confirmed that although the condition shares somegenetic features similar to myeloma, on the whole it is different and lackssome of the “high-risk” chromosome abnormalities seen in myeloma thatare normally associated with a poorer prognosis. Also presented was astudy in which doctors from the National Amyloidosis Centre investigatedthe addition of a drug, doxycycline, to standard treatment in patients wherethe amyloidosis has affected the heart. The results suggest some benefit for patients with cardiac amyloidosis from the addition of doxycycline butfurther work is needed to confirm these findings.

New approach for tackling amyloid depositsResearchers in California have discovered a way to reduce secretion of theabnormal proteins (which build up as amyloid deposits in AL amyloidosis)from cells in the bone marrow which could act as a potential new target forfuture treatment. In AL amyloidosis, an abnormal protein secreted byplasma cells forms fibrils which deposit and damage organs such as theheart, kidney and gut. Current treatment for AL amyloidosis useschemotherapy to kill the plasma cells. This treatment is not specificallytargeted and has many side-effects. The researchers found that activationof a protein called ATF6 reduced the secretion of the abnormal amyloidforming proteins from a part of the human cell called the endoplasmicreticulum, which is responsible for folding proteins and secreting them intothe blood. Furthermore, they showed that activating ATF6 decreased theaggregation of amyloid by around 75%, suggesting the potential to reducedisease. The next step is to identify drug candidates that can activate ATF6.

News&Notes

2 l AL amyloidosis Matters SPRING 2015

AL amyloidosis Matters SPRING 2015 l 3

Around 60 people attended the most recent Patient and Family AL amyloidosis Infoday held in London in September to learn about thelatest research into AL amyloidosis and updates on current treatmentsfrom experts.

Dr Julian Gillmore started theInfoday with an introduction to AL amyloidosis. He talked abouthow AL amyloidosis is caused by anunderlying bone marrow disorder,where abnormal plasma cells in thebone marrow produce the amyloidprotein. This abnormal protein foldsand forms fibres (called fibrils) whichprevents it being cleared by thebody; fibrils infiltrate and damageorgans. AL amyloidosis can affectany organ and the SAP (serumamyloid P) scan is used to showhow amyloid is distributed in organsand to help monitor whether amyloiddeposits are being removedfollowing treatment (calledregression). Treatment for ALamyloidosis aims to help regressionby reducing the amount of amyloidbeing produced by the body.

Dr Wechalekar then talked abouttreatment for AL amyloidosisexplaining how this consists ofcombinations of different drugswhich work together to kill theabnormal plasma cells producingthe amyloid protein. Treatment isgiven in four week cycles thatcontinue until the best response isachieved (usually this takes betweenfour and six cycles). He also talkedabout some of the newer treatmentsbeing used in AL amyloidosisincluding Imnovid® (pomalidomide)

and bendamustine which areavailable on the Cancer Drugs Fundfor patients who have already had anumber of prior treatments. Othertreatments which are in, or about tostart, clinical trials are ixazomibcitrate and Kyprolis® (carfilzomib) – both similar drugs to Velcade –and daratumumab, a monoclonalantibody.

Prof Philip Hawkins gave an update on new developments indiagnosis, in particular how newtests are helping to distinguish AL amyloidosis from other types ofamyloidosis. He also gave a briefupdate on the research being led by Prof Sir Mark Pepys FRS todevelop an entirely new type oftreatment for AL amyloidosis, which is being developed withGlaxoSmithKline and has nowcompleted a Phase I clinical trial.

Dr Helen Lachmann then gave apresentation about thecomplications and side-effects of AL amyloidosis and its treatment,explaining that the commonestorgans affected at diagnosis are the kidneys and the heart. ALamyloidosis and its treatment canproduce a lot of side-effects andcomplications which can be difficultto manage but Dr Lachmannexplained what can be done to

manage cardiac failure, nephroticsyndrome (when damaged kidneysleak protein), postural hypotension,fatigue, nausea, diarrhoea and pain.

Dr Marianna Fontana talked abouta new cardiac imaging technique.Cardiac amyloid is one of the mostserious and common problems forAL amyloidosis patients. Healthcareprofessionals have had to rely onECHO (echocardiogram) scanswhich can indicate the presence ofamyloid protein due to a thick heartwall. ECHO is a very important testto demonstrate heart function but itcan’t prove that any thickening ofthe heart wall is due to amyloid –often this is more commonly relatedto high blood pressure. A newtechnique called an equilibriumcontrast MRI test can nowdistinguish between thickening dueto high blood pressure and amyloid,and show the amount of amyloid inthe heart muscle.

The Infoday ended with an excellentpatient experience talk from HillGaston who talked about how hewas diagnosed with AL amyloidosis,his treatment so far and how he hasadjusted his lifestyle to cope with AL amyloidosis.

You can watch videos of the talks given at the AL amyloidosisInfoday at www.myelomatv.org.uk

A report on the AL amyloidosisInfoday 2014Author: Sue Perkins, Service Development Manager

Special feature

Prof Philip Hawkins at the Infoday with Dr Ashutosh Wechalekar


INTRODUCTION Kidney disease is very common in ALamyloidosis patients. Kidney diseaseusually develops slowly (this is calledchronic kidney disease). Amyloiddeposits in the kidneys typically makethe kidneys leak proteins and mayalso affect the ability of the kidneys to filter the blood. This can lead to acondition called nephrotic syndromein which the lower legs typicallybecome swollen. In some cases,amyloid deposits mean that thekidneys can no longer purify theblood; this is called kidney or renalfailure. If kidney disease is severe,function of the kidneys may need tobe replaced by a treatment calleddialysis to purify the blood.

WHAT DO THE KIDNEYS DO?The kidneys carry out many essentialfunctions, including:

• Filtering the blood to get rid ofwaste products from thebloodstream

• Keeping the salt (e.g. sodium andpotassium) and water content of thebody constant

• Controlling blood pressure

• Producing a number of essentialhormones e.g. erythropoietin whichis essential for the production of redblood cells in the bone marrow, andan enzyme called renin which playsan important role in regulating blood pressure

WHAT ARE THE SYMPTOMSOF KIDNEY DISEASE?When the kidneys are not workingproperly, harmful toxins and excessfluids build up in the body, whichcauses symptoms.

The symptoms of kidney diseasemay include:

• Thirst

• Fatigue

• Persistent headaches

• Loss of appetite

• Nausea and/or vomiting

• Passing excessive amounts ofurine, or very little or no urine

• Swelling in the lower legs(oedema)

• Shortness of breath

This article covers kidney disease in AL amyloidosis, explaining what the kidneys do, symptoms of kidneydisease and some of its complications and treatment.

Although high blood pressure is acommon occurrence in kidneydisease, it is rare in AL amyloidosis.Certain drugs help both the bloodpressure and the kidneys to functionmore efficiently - they are routinelyused in many patients with kidneydisease. However, these drugs (likeramipril or losartan) need to be usedwith caution or avoided completely,particularly if there are amyloiddeposits in the heart or if your bloodpressure is already normal or low. If you are being treated for highblood pressure it is important tomake sure your doctor knows aboutyour amyloidosis. If they are not surehow to deal with this, it may behelpful to suggest they contact theNational Amyloidosis Centre.

Medical MattersAL amyloidosis and kidney diseaseAuthor: Jude Leitch, Patient Information Specialist


Nephrotic syndrome is an abnormalcondition of the kidney where largeamounts of a blood protein calledalbumin leaks from the blood into theurine. This in turn causes water toleak out of the blood vessels into thetissues causing swelling (oedema),particularly in the lower legs.

The oedema of nephrotic syndromegenerally requires treatment withdiuretics, often called water tablets.These are drugs which help yourkidneys to pass more fluid andtherefore help to reduce the swellingin the lower legs. These drugs workbest with strictly controlling salt andfluid intake. Your doctor will adviseon the exact details.

TREATMENT If treatment for AL amyloidosis itself –involving chemotherapy, steroids andnewer drugs such as Velcade andRevlimid® – is successful, the build-up of new amyloid deposits in thekidneys should be reduced orstopped which may stop furtherdamage to the kidneys. The proteinleak from the kidneys improves andkidneys can heal the damage, butkidney function already lost usuallydoes not improve. Diuretics andcareful maintenance of fluid balancethrough salt and drinkingrestrictions are used as supportivetreatment for patients withAL amyloidosis affecting the kidneys.

DIALYSIS Dialysis is a form of treatment thatreplicates many of the kidney’sfunctions. It is often used to treatsevere kidney disease, where thekidneys have lost most or all of theirfunction.

There are two types of dialysis,haemodialysis and peritoneal dialysis.

Haemodialysis is carried out byinserting a dialysis line (a plastic tube)

ANY QUESTIONS?Call our Infoline on 0800 9803332 or visitwww.myeloma.org.uk/amyloidosis

KIDNEYS IN 10 SECONDS

• The kidneys carry out manyessential functions, includingfiltering the blood of wasteproducts

• When the kidneys are notworking properly, harmful toxins and excess fluids build up in the body which causessymptoms such as thirst,shortness of breath and swelling

• Diuretics and carefulmaintenance of fluid balance are used as supportivetreatments for patients with AL amyloidosis affecting thekidneys

into a vein in the top of the leg or theneck. This line is then attached to amachine that pumps blood througha filter. This gets rid of wasteproducts and excess fluids. After theblood has passed through the filter itis returned to the body. Each dialysistreatment takes up to four hours andis usually required at least threetimes a week.

Peritoneal dialysis involves using theperitoneum as a filter. Theperitoneum is a thin membrane(covering) that surrounds andsupports the abdominal organs,such as the stomach and liver.During peritoneal dialysis, a smallflexible tube, known as a catheter, isattached to an opening in thestomach. A special dialysis fluid isintroduced into the space thatsurrounds the peritoneum. As bloodmoves through the peritoneum,waste products and excess fluid aremoved out of the blood and into the dialysis fluid. The dialysis fluid isthen drained from the body. Theprocess of peritoneal dialysis lastsroughly 30 to 40 minutes and isrepeated around four times a day.Alternatively, it can be run overnight.

There is no evidence to suggest ifone form of dialysis is better than theother in AL amyloidosis.

KIDNEY TRANSPLANTATIONTransplantation is suitable for somehighly selected patients with ALamyloidosis due to concerns aboutthe possible recurrence of amyloid inthe transplanted kidneys as well asfitness for a major surgicalprocedure. It can be considered inselected patients whose underlyingplasma cell disorder has beenbrought under control bychemotherapy and who areotherwise fit and healthy.

SUMMARY Kidney disease is very common in AL amyloidosis patients. Amyloiddeposits in the kidneys typically make the kidneys leak proteins andmay also affect the ability of thekidneys to filter and purify the blood.The symptoms of kidney diseaseinclude shortness of breath andoedema. Treatment of the ALamyloidosis itself, diuretics and carefulmaintenance of fluid balance shouldhelp to improve kidney function.Dialysis may be required in severecases, and transplantation is apossibility in a minority of patients.

It appeared that AL amyloidosis andI had known one another for severalmonths before being formallyintroduced in March 2011.

At that time, I was 47, fit and healthy.I didn’t drink or smoke and observeda balanced diet. Living in a Fifevillage, I was also an enthusiasticleisure cyclist.

An incurable illness was not on myradar!

However, my journey began inNovember 2010 when I visited myGP with suspected prostatitis. I alsomentioned that I was feeling queasymost of the time and had a pain justbelow my right rib cage.

By late January 2011, the prostateproblem was away but othersymptoms were increasing. I wasstarting to get sick, sometimes withblood, and with an intensity that I’dnever known before. On oneoccasion, I blew the blood vesselssurrounding both my eyes just frombeing sick. Within days, my feet,ankles and legs had swollen toabout twice their normal girth. Icontinued to work and cycle, butwas becoming increasinglybreathless and fatigued.

My GP arranged for me to get anultrasound. She was concerned thatthere was something happening inrelation to my liver. There was alsoraised protein level in my urine,which suggested that there might bekidney involvement too. I didn’tmake it as far as my next


appointment. Knowing that Icouldn’t go on, I presented at theA&E department of Queen MargaretHospital, Dunfermline, and I wasadmitted.

In early March 2011, for two weeks,I underwent a variety of tests. Otherthan knowing that I was ‘nephrotic’(swollen ankles/legs etc), nodefinitive diagnosis could bemade. My cholesterol shot off thescale at 25! Eventually, the decisionwas made to carry out a kidneybiopsy to get a tissue sampleanalysed. This was the turningpoint. The biopsy itself was relativelypainless, if a little uncomfortable. Asthe risk of bleeding from the kidneyscan be quite high, it’s important thatthey target the area accurately. I hadno problems in this respect.Returned to the renal ward, I wasinformed by my Renal Consultant,Dr Alfonzo, that amyloid had shownup in the biopsy analysis. Slowly butsurely, as she explained that ALamyloidosis was a very rarecondition, and was potentially life-shortening, my horizons started tocloud. Although they had detectedamyloid, the doctors in Dunfermlinecouldn’t say which type it was, theextent of it and what my survivalchances were. This would require areferral to the National AmyloidosisCentre (NAC) at the Royal FreeHospital in London. First, I had toget a bone marrow biopsy.

This was organised immediately and

I was introduced to myHaematology Consultant, DrMcLintock, who carried out theprocedure. Where the kidney biopsywas relatively painless, the bonemarrow biopsy was very painful, butonly for a small number ofseconds. Dr McLintock explainedthat survival rates for people with AL amyloidosis were notgreat. Without knowing how theextent of my AL amyloidosis andhow the amyloid deposits hadaffected my organs, it was too earlyto get a prognosis. This would onlycome after the visit to the NAC. So,with this information, I phoned mywife, Audrey, and tried to give herthe basic information that I’d justbeen given. Inevitably, we were bothstunned and unsure of how toapproach the future.

I went home, not really knowinghow I was going to share thisinformation with family and thoseclose to me.

Our daughter, Alison, was workingin Austria as a teaching assistant atthe time and our son, Nathan, wasa student at the University ofAberdeen so also living away fromhome. In Ali’s case, we had to breakthe news by Skype. Within twoweeks of leaving Queen MargaretHospital, Nathan and I were at theNAC in London. Happily, everyonethere was extremely pleasant,helpful and reassuring.

My visit was split over two days. In

Patient experience

Mark McConway is married to Audrey and has two children. Here he talks about his experience of AL amyloidosis, including how he was diagnosed, his treatment and a fundraising cycle he completed in May 2014.

‘An incurable illness wasnot on my radar’


addition to similar blood and urinetests that I’d had previously, I wasalso injected with radioactive dye onDay 1. On Day 2, I had my very firstSAP scan. It took around half anhour and was pretty much like atypical MRI scan, through the donutshaped tunnel. No problems. Then Imet with Dr Julian Gillmore. He wasfriendly, professional and providedsome much needed reassurance.

He asked if I’d done any of my ownresearch on AL amyloidosis sincegetting the news. Up until then, I haddone some trawling of sites on theinternet but they didn’t add much towhat I’d learned from a Myeloma UKnewsletter I’d picked up, by chance,in my local hospital, waiting for tests.

He then told me I had AL – orsystemic – amyloidosis. He said itwas being produced in my bonemarrow and was of the ‘light chain’type. He told me it was affecting myliver, kidneys, spleen and that therewere early indications that my heartwas also involved. He told me thatAL amyloidosis is an incurablecondition at this time and that theprospects are not verygood. However, he said that in myparticular case he was prettyconfident that my AL amyloidosiscould be treated to help my body toclear the existing amyloid deposits.He went on to explain that myorgans were in pretty good conditionand nothing had failed yet. There areno guarantees, but if they couldattack the production of amyloid inmy bone marrow, they could turnthe ‘tap’ off and allow the existingamyloid to eventually escape mybody.

He thought I would be getting backto fitness in about two years, but thekey thing was to start thechemotherapy as soon as possible.He said I would probably feel a lotworse before I started to feel better.

Mark with Prof Philip Hawkins and Tom McLucas

Treatment for me involvedswallowing a lot of tablets, whichtook a bit of getting used to,especially as my fluid intake wasrestricted to 1 litre per day. Theprincipal treatments werecyclophosphomide,dexamethasone, thalidomide and a Fragmin® injection once a day, but I also required furosomide andspironolactone to reduce the fluidand domperidone as anti-sickness.In total, I would take approximately560 tablets every 21 day cycle for 5 cycles, taking me up to mid-summer 2011.

In order to keep track of the tablets I was taking, and my outcomes eachday, I built a ‘cloud’ database andrecorded everything as frankly as I could. In retrospect, it makesgruesome reading in places butdemonstrates a clear and positivetrajectory as far as being ontreatment is concerned.

My taste was inevitably affected andmost food became inedible for awhile. The one notable exception

was a pleasurable (if ghastly to theobserver!) addiction to roll-mopherring, pickled onion and beetroot.

As my light chain levels came downtowards the normal range, I was stillvery weak, having lost nearly 10kg,weight I could ill afford to shed(60kg is my normal weight).

Three months after finishing thechemotherapy, I did my first bikeride of 5 miles. By the end of 2012, I had cycled 1,000 miles.

In May 2014, I arrived for my latestappointment at the NationalAmyloidosis Centre, having cycled507 miles over six days to get there,along with my friend and cyclingbuddy Tom McLucas, and with mybrother, Matt, providing the logisticalsupport. In the process, wemanaged to raise over £2,000 forthe Amyloidosis Research Fund.

I still have days where exhaustiontakes a hold and I have to sleep.The trick, I’ve learned, is just toaccept that this is the way thatthings are now – at least until a cureis found.

If you are interested in sharing your experience please contact Sue Perkins on 0131 557 3332 [email protected]

Martin with Jodey-Marie

Fundraising news

To raise money for AL amyloidosisresearch or the support andinformation services provided byMyeloma UK, call our FundraisingTeam on 0131 557 3332 or [email protected]

Myeloma UK Broughton House, 31 Dunedin Street, Edinburgh EH7 4JG Tel: 0131 557 3332Email: [email protected] www.myeloma.org.uk/amyloidosis Charity No. SC 026116

Family duo conquer Ditchling Beaconin aid of AL amyloidosis researchMartin Bolton-Smith’s wife Cherylwas diagnosed with AL amyloidosisin 2011. The shock of Cheryl’sdiagnosis with this rare, incurablecondition persuaded Martin that hehad to actively try to help Cheryl bydoing something positive himself tosupport the work of doctors andresearchers at the NationalAmyloidosis Centre. Martintherefore set himself a challenge ofraising £20,000 in three years foramyloidosis research.

By day Martin is a London cabbieand he has organised a number ofcabbies’ collection at Heathrowairport as part of his three yearfundraising challenge. He is verygrateful to his cabbie colleagueswho have raised about £3,000 forthe Amyloidosis Research Fundthrough these collections. Duringthe three years since Cheryl’sdiagnosis, Martin himself has alsopromoted social events, organisedclay pigeon shoots, run the BarnesGreen half marathon, the Brightonmarathon and swum the equivalentdistance of The English Channel in12 weeks in Horsham pool.

To top off his three years offundraising before taking a well-earned break, Martin chose toparticipate in the Doitfor charityLondon to Brighton cycle ride inSeptember 2014. He was joined byCheryl’s cousin Jodey-Marie Wilsonand husband Barry, plus theirdaughter Abbie, who is aged six,helped their efforts by making aspecial amyloidosis awarenessbracelet for the occasion.

Martin and Jodey joined 3,000competitors participating in the bikeride with Barry providing support inthe back up vehicle. They got up at3.00am on the morning of theevent to drive to ClaphamCommon for the start of the ride. Itwas a beautiful September day forthe 54 mile ride across the Sussexcountryside and a challengingsection in the South Downs.

A particularly difficult part of in theride is Ditchling Beacon (elevation248m), notorious for losing ridersfrom the professional pelotons inthe UK stage of The Tour de Franceand also in the Tour of Britain.Martin was delighted to havecompleted cycling DitchlingBeacon without having to stop,though Jodey, like many other

competitors, decided to take it easyand walk the steepest section. Aftercompleting Ditchling Beacon andcycling into Brighton, Jodey andMartin crossed the finishing linetogether; as Martin said, “Westarted as a team, rode as a teamand finished as a team.”

Before Cheryl’s illness Martin wasmore of a sports’ spectator than aparticipator, so the sporting eventshe has undertaken have been apersonal challenge for him. Havingcompleted runs, swims and theLondon to Brighton cycle, Martin’sview is that the hard work trainingfor, and completing, the variousevents cannot compare with whatCheryl has to cope with each day.Completing the London to Brightoncycle ride helped Martin to exceedhis three year fundraising target,meaning in total he has raised in theregion of £23,000. This is asignificant achievement which hasalso helped to raise awareness ofAL amyloidosis and inspired othersaffected by the condition tofundraise too.

Martin will now be taking a wellearned break from fundraising,knowing his efforts have helped toraise awareness of AL amyloidosisand vital funds for research.

“Everything went so well” wasMartin Bolton-Smith’s verdict atthe end of the DoitforcharityLondon-Brighton cycle ride inSeptember.

issue 7 spring 2015 al amyloidosis matters

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