State of the nation in multiple myeloma – a UK perspective

State of the nationin multiple myeloma –a UK perspective

This report was supported by an educational grant from Amgen

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State of the nation in multiple myeloma – a UK perspective is supported by an

educational grant from Amgen. Written by an independent medical writer, on behalf of

Hayward Medical Communications, the report is based on the discussions and

consensus of a multidisciplinary expert group during a meeting held in London on 19

January 2016. The meeting’s objectives were to:

• Address the clinical, economic, public health and patient perspectives of multiple

myeloma throughout the UK, to really understand the current ‘state of the nation’

• Discuss key topics within each of these four areas using perspectives to understand

the current challenges faced, and subsequent visions for the future.

The experts who attended the meeting and contributed to this report are:

• John Ashcroft, Consultant Haematologist, University of York and Mid-Yorkshire

Hospitals

• Gordon Cook, Consultant Haematologist, University of Leeds and Leeds

Teaching Hospitals

• Sarah Henshaw, Myeloma Specialist Nurse, Nottingham University Hospitals

• Graham Jackson, Consultant Haematologist, Newcastle upon Tyne Hospitals

• Matthew Jenner, Consultant Haematologist, University Hospital Southampton

• Zack Pemberton-Whiteley, Head of Campaigns and Advocacy, Leukaemia Care

• Karthik Ramasamy, Consultant Haematologist, Oxford University Hospitals

• Sophia Skyers, Chair, Basil Skyers Myeloma Foundation

• Chris West, Head of Media and Public Affairs, Bloodwise

An additional expert unable to attend the meeting but who has provided expert opinion throughout the developmental stages of this report is:

• Eric Low, Chief Executive, Myeloma UK

Amgen provided an unrestricted educational grant for the multidisciplinary expert groupmeeting and writing of this report, and reviewed the document for technical accuracy only.

About this report

OverviewThe management of, and outlook for, patients with myeloma is virtually unrecognisablefrom 40 years ago. Significant improvements in life expectancy and quality of life havebeen brought about by the introduction of novel biological agents and an increasedunderstanding of the biology of the disease, alongside improvements in supportive care. Those working in myeloma report a genuine enthusiasm and collaborativeapproach driven by the desire to improve life for those affected by this chronic andincurable disease. This has resulted in truly equal partnerships between patients, carers,policy-makers and healthcare professionals.

This report investigates how myeloma treatment and the factors influencing care for myeloma patients have changed over the last 40 years. It addresses not onlyongoing issues in myeloma care provision, but also looks to highlight the remaininghurdles within this disease area and how we might overcome them. Finally, it offers a‘call to action’ for all stakeholders, for continued collaboration to improve patient careover the coming decade and beyond.

What is myeloma?Myeloma is a complex haematological cancer thatdevelops from plasma cells (a type of blood cell) in-side the bone marrow.1–3 In patients with this dis-ease, the bone marrow produces increased numbersof abnormal plasma cell clones. Plasma cells nor-mally produce immunoglobulins to fight infectionbut the abnormal clones are unable to do so, and arepresent in such high numbers that they can influ-ence the function of the bone marrow in terms of theproduction of normal bloods cells – white blood cellsthat fight infection, red blood cells that carry oxygenand platelets that facilitate clotting.2 As myelomamay affect bone marrow at multiple bony sites it isoften called multiple myeloma.

Evidence strongly suggests that myeloma is al-most always preceded by an asymptomatic prema-lignant phase described as monoclonal gammopathyof undetermined significance (MGUS).4–6 However,not all cases of MGUS progress to myeloma.7 Somepatients also have an intermediate, more advancedasymptomatic stage – smouldering multiplemyeloma (SMM) – which is much more likely toprogress to myeloma than MGUS (10% per year ver-sus 1% for MGUS).8,9

What are the symptoms of myeloma?Early myeloma may be asymptomatic, but the im-pact of the disease on healthy blood cell productionin the bone marrow typically results in recurrent andpersistent infections due to the lack of white bloodcells, breathlessness and tiredness resulting fromanaemia caused by the lack of red blood cells, andabnormal bruising and bleeding due to the lack ofplatelets, which may occur later in the disease or asa side effect of treatment (Box 1).2,6

As the excess abnormal plasma cells change thebone microenvironment, patients may develop bonedisease, including pain, fractures in the absence oftrauma (pathological fractures), hypercalcaemia andspinal cord compression. Consequently, their qualityof life may be significantly reduced.2,6,10 Hypercal-caemia can result in confusion, coma, muscle weak-ness, pancreatitis, constipation, thirst, polyuria,shortening of the QT interval and acute renal insuf-ficiency.2,6 Spinal cord compression is a serious com-plication that can occur when bone fragments fromvertebrae collapse or deposits of plasma cells com-press the spinal cord resulting in pain and tendernessin the spine, weakness or paralysis of the lower limbs,and loss of bladder and bowel control, which can be-come permanent without urgent treatment.6,7,11

Patients may also develop renal impairment,which is already present in 20–25% of patients with

myeloma at presentation and develops in up to 50%of patients, and hyperviscosity syndrome, which cancause blurred vision, headaches, mucosal bleedingand dyspnoea due to heart failure.6,7,11

How common is myeloma and who does it affect?Approximately 5,500 people are diagnosed withmyeloma in the UK each year, equivalent to 15 peo-ple per day.12,13 In 2013, it was the seventeenth mostcommon cancer in the UK, accounting for 2% of allnew cases of cancer.12,13 It is the second most com-mon haematological malignancy.14

Myeloma is the fifteenth and eighteenth mostcommon cancer in men and women, respectively,

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State of the nation in multiple myeloma – a UK perspective

About myeloma

The changing face of myeloma

over the past 40 years

Key ongoing issues in myeloma

Visions for myeloma 2025

1. About myeloma

Box 1: Clinical features of myeloma.2,6

• Recurrent and persistent infections • Abnormal bruising and bleeding • Anaemia, resulting in breathlessness and tiredness • Bone disease/pain/deformity • Hypercalcaemia • Renal dysfunction• High ESR• High levels of immunoglobulin causing hyperviscosity• Spinal cord compressionESR=erythrocyte sedimentation rate.

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with around 3,100 new cases in men and 2,400 inwomen each year.12,13 The lifetime risk of developingmyeloma in 2012 was around one in 115 for men andone in 155 for women.12,13 Age-standardised inci-dence rates for men and women differ significantlybetween the nation states of the UK.13

The incidence of myeloma increases sharply with age. Only 16% of patients are <60 years; 59% of cases in the UK between 2011 and 2013 were diagnosed in people aged ≥70 years. The me-dian age at presentation is approximately 70 years.15

Rates peak in males aged 80–84 and in females aged 85–89 years, before decreasing in those aged ≥90 years (Figure 1).13,16 Between the ages of35–39 years, the incidence rate is higher in men thanin women.13

The age-standardised incidence of myeloma issimilar for Asian and white people but significantlyhigher for black people (Table 1).5,12,13 Indeed, blackpeople are disproportionately affected not only be-cause of the two to three-fold higher incidence ofmyeloma, but also due to its earlier onset (it is diag-nosed on average four years earlier in black peoplethan white people) and a higher incidence of MGUS(albeit with a similar rate of progression).14 Further-more, black men have a higher disease burden thanblack women.14 The reasons for these racial differ-ences are uncertain.14 The incidence of myelomaseems to be lower in people living in more deprivedareas, but this may be due to a lack of recognition ofsymptoms rather than a truly lower incidence.13

Risk factors for myeloma are poorly understoodbecause the condition is rare, but various factors areassociated with the development of myeloma (Table2).2,17 However, each year less than 1% of cases in theUK are linked to preventable modifiable factors.17

What is the outlook for myeloma patients?Although myeloma is not curable, it is treatable.7

Survival has quadrupled in the past 40 years in theUK,12 as more treatments have become available andsupportive care has improved patients’ quality of life.Improvements in relative survival have also beenseen over the past decade. Five-year survival has in-creased from 30% in men diagnosed in 2000–2003to 40% in those diagnosed in 2008–2010, and from28% to 39% in women diagnosed over the same pe-riod.1 In England and Wales in 2010–2011, 77% of

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State of the nation in multiple myeloma – a UK perspectiveAbout myeloma





Figure 1: Average numberof new cases of myelomaper year and age-specificincidence rates per100,000 population inthe UK, 2011�2013.Reproduced withpermission from CancerResearch UK.13

Table 1: Age-standardised incidence of myeloma per 100,000 population in the UK.12,13

Racial group Men Women

White 6.1–6.5 3.9–4.2

Asian 3.6–6.4 2.3–4.4

Black 10.9–18.2 6.6–11.5

Table 2: Risk factors for myeloma.2,17

Non-modifiable Modifiable

• Age• Sex• Race• Family history• Genetic conditions, such as Gaucher disease• Autoimmune conditions:

– pernicious anaemia– ankylosing spondylitis– autoimmune haemolytic anaemia– systemic lupus erythematosus

• Lowered immunity due to drugs to prevent rejection ofsolid organ transplantation

• HIV

• Overweight/obesity• Occupational exposure:*

– radiation (e.g., X and gamma radiation)– benzene– ethylene oxide

*Evidence on causality is conflicting.

750

600

450

300

150

0

75

60

45

30

15

0

Aver

age

num

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ear

0 to04

05 to09

10 to14

15 to19

20 to24

25 to29

30 to34

35 to39

40 to44

45 to49

50 to54

55 to59

60 to64

65 to69

70 to74

75 to79

80 to84

85 to89

90+

Age at diagnosis

Rate

per

100

,000

Male rates Female rates ■ Male cases ■ Female cases

patients were still alive one year after diagnosis, 47%at five years and 33% at ten years (Table 3).12,13,18 Theone-year survival rate ranges from 77% to 85% formost routes of diagnosis, but is only 53% for thosewho present through emergency routes, emphasis-ing the importance of early diagnosis.19 As details ofrace are not collected with prevalence data, the out-look, outcomes and treatment responses specific forblack patients are uncertain.

Although survival from myeloma has improvedin the past decade, it is still the sixteenth most com-mon cause of death from cancer in the UK, with ap-proximately 1,500 men and 1,300 women dyingevery year, equivalent to more than seven peopleeach day.12 Indeed, mortality in the UK is the sev-enth highest in Europe for men and the tenth high-est for women.12

How is myeloma diagnosed?Diagnosis is based on a combination of clinical fea-tures at presentation, laboratory tests and imaging7

– the latter two are also useful to distinguish be-tween symptomatic myeloma requiring treatment,SMM and MGUS.7

Some patients are diagnosed when they presentwith symptoms; others, however, particularly thosewith early disease, may be diagnosed incidentallyafter abnormal laboratory results identified duringroutine tests.6 The vast majority of patients in Eng-land are diagnosed after a routine or urgent GP re-ferral (35%) or emergency presentation (34%)(Figure 2).19,20 The proportion of patients presentingas an emergency is higher than the average for many other cancers (for example, 22% for all malig-nant neoplasms, excluding non-melanoma skin cancer), which may indicate later diagnosis ofmyeloma20 or the fact that myeloma causes bonepain, fractures and renal failure warranting hospitaladmission, whereas other cancers do not tend to unless metastatic.

What treatments are available?Myeloma remains incurable other than in a verysmall proportion of patients who are cured by allograft. However, a combination of specific disease-directed treatments and supportive care canbe used to:6,21

n Provide disease controln Relieve symptoms and complicationsn Extend and improve the quality of patients’ lives.

Patients with asymptomatic myeloma do notusually require active treatment other than support-ive measures and close monitoring by a consultant

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About myeloma





Table 3: Survival rates in adults aged 15–99 years in England and Wales, 2010–2011, and prevalence of myeloma in the UK at 31 December 2006 by years since diagnosis.12,13,18

Population Survival (%) Prevalence (n)

1 year 5 years 10 years 1 year 5 years 10 years

Men 77.9 49.8 36.6 1,595 5,247 6,921

Women 75.1 43.8 28.1 1,294 4,175 5,544

Total 76.6 47.0 32.5 2,889 9,422 12,465

Figure 2: Routes of diagnosis for patients with myeloma in England, 2006—2013.19

40

35

30

25

20

15

10

5

0

3

Routine orurgent GP

referral

Emergencypresentation

Two-weekwait referral

Anotheroutpatient

route

Inpatientelectiveroute

Route ofdiagnosisunknown

Referral route

35 34

1412

2

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nts

(%)

Figure 3: Treatment pathway for transplant-eligible patients. Adapted from Ludwig et al (2014)and from Durie et al (2003).10,24

Diagnosis and staging

Induction therapy Sub-optimal response

Consider alternativetherapy

Anti-myeloma therapy

Stem cell collection

Stem cell transplantation(with high dose therapy)

Further therapy

haematologist;6 although emerging evidence indi-cates that earlier treatment of myeloma may be ben-eficial.22,23 Treatment should be initiated in allpatients with end-organ damage, which may includebone lesions, anaemia, myeloma-induced renal im-pairment and hypercalcaemia.10 Patients on treat-ment should be carefully monitored for response totherapy, symptoms and toxic sequelae.10

The broad treatment pathway, which includeshigh-dose therapy and autologous stem cell trans-plantation (HDT-ASCT), for younger, fitter patients,preceded by induction therapy,10 is summarised inFigure 3. However, because the incidence ofmyeloma is highest in the older population, ASCTwill be deemed unsuitable for most of these pa-tients; therefore, they will receive inductionchemotherapy alone without consolidation withASCT. Induction regimens almost always involve acombination of complementary drugs given in cycles of several weeks to months,21 which may in-clude chemotherapy such as cyclophosphamide andmelphalan, steroids such as dexamethasone andprednisolone, and other drugs such as thalidomide,

bortezomib and lenalidomide.21 Table 4 summarisesthe current treatment options for newly diagnosedmyeloma patients who do not want to enter a clini-cal trial (Jackson G, personal communication,2016).

For those patients who present with a relapsethat requires further treatment, the addition of a second HDT-ASCT may be beneficial.33 In those patients who are ineligible for transplant, a new lineof treatment may be initiated or the first treatment may be repeated as long as it led to an initial response, was well tolerated and lasted more than six months.10

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Table 4: Examples of treatment options in the UK for newly diagnosed myeloma patients who do not want toenter a clinical trial (Jackson G, personal communication, 2016).25–32

Line of therapy Eligible for ASCT Not eligible for ASCT

1 VTD/VCD followed by ASCT without maintenance VMP or CTDa

2 PAD/VCD and ASCT without maintenance Bortezomib–dexamethasone ± cyclophosphamide

3 Lenalidomide and dexamethasone until progression Lenalidomide and dexamethasone until progression

4 Panobinostat–bortezomib plus dexamethasone orbendamustine or pomalidomide or trial or palliation

Panobinostat–bortezomib plus dexamethasone or bendamustineor pomalidomide or trial or palliation

5 Trial or palliation Trial or palliation

ASCT=autologous stem cell transplantation; CTDa=attenuated regimen of cyclophosphamide–thalidomide–dexamethasone; PAd=bortezomib–doxorubicin–dexamethasone; VMP=bortezomib–melphalan–prednisolone; VCD=bortezomib–cyclophosphamide–dexamethasone; VTD=bortezomib–thalidomide–dexamethasone.

Table 5: Supportive care interventions for key complications of myeloma.7,34,35

Complication Intervention

Anaemia • Erythropoietin analogues, as per NICE guideline NG35• Red blood cell transfusions for patients with severe

symptoms and those not responding to or eligible forerythropoietin

Bone disease • Bisphosphonates• Calcium and vitamin D• Local radiotherapy• Surgery in case of fractures or fracture risk• Kyphoplasty and vertebroplasty for complications

of spinal fracture/collapse

Infection • Vaccination for influenza A and B, pneumococci,Haemophilus influenza

• Prophylactic antibiotics for patient at high risk• Antiviral prophylaxis for patients receiving bortezomib• Prompt action in case of documented infection

Pain • Local radiotherapy or surgical intervention• Analgesics• Kyphoplasty and vertebroplasty

Polyneuropathy • Close monitoring and gentle massage with emollients• Dose and/or schedule adjustments• Pregabalin/gabapentin/amitriptyline

Venousthromboembolicevents

• LMWH or warfarin for patients startingimmunomodulatory drugs

• Aspirin if LMWH or vitamin K antagonists are unsuitable

Key: LMWH=low molecular weight heparin; NICE=National Institute for Health and Care Excellence.

Box 2: Symptoms and side effectsof myeloma treatments addressedby supportive care.6,34

• Anaemia• Anorexia• Bisphosphonate-induced

osteonecrosis of the jaw• Bone complications• Constipation• Diarrhoea• Fatigue• Haemostasis and thrombosis• Infection• Mucositis• Nausea• Pain• Peripheral neuropathy• Sedation• Vomiting

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Although chemotherapy has significantly pro-longed survival, many patients live with the burdenof the complications of the disease itself, and the cumulative side effects of treatment; therefore, sup-portive care is crucial (Box 2).34 Supportive strategies

are summarised in Table 5. Supportive managementmay also include complementary therapy, holisticneeds assessment and palliation/end-of-life care34 –this is particularly important given the relativelyhigh mortality still associated with the disease n

S Myeloma is almost always preceded by MGUS,6 but not all cases of MGUS progress to myeloma7

S About 5,500 people are diagnosed with myeloma in the UK each year, equivalent to 15 people a day;12,13 in 2013,

it was the 17th most common cancer in the UK, accounting for 2% of all new cases12,13

S Myeloma is more common with increasing age, in men versus women and in black people versus white people5,12–14

S Survival from myeloma has improved, with about one-third surviving their disease by ≥10 years and about half by ≥5

years in England and Wales12,13,18

S Myeloma is still the 16th most common cause of death from cancer in the UK, with about 1,500 men and 1,300

women dying every year from myeloma, equivalent to more than seven people every day12

S Myeloma remains incurable, but treatments can provide disease control, relieve symptoms and complications,

and extend and improve the quality of patients’ lives6,21

S Asymptomatic myeloma usually requires no treatment other than supportive care and close monitoring6

S Supportive care is a major component of the management of patients with myeloma, helping patients to deal

with the symptoms and complications of the disease

2. The changing face of myeloma over the past 40 years

As the epidemiological data illustrate, the overalloutlook has significantly changed for patients diagnosed with myeloma over the past 40 years.These changes are the result of the availability ofnovel therapeutics, advances in science and an in-creased understanding of the disease, and are re-flected in changing patterns in the patient journeyand clinical care pathway, as well as changes interms of health policy.

The past few decades have seen massivegrowth in our understanding of thescience underlying blood cancers ingeneral, but particularly myeloma… We now know that myeloma is a heterogeneous dis-ease, underpinned by several genetic abnormalitiesdetectable at various stages – for example, sympto-matic multiple myeloma, SMM, MGUS and solitaryplasmacytoma of the bone.6 The natural diseasecourse varies between individuals, with survivalranging from a few weeks to more than 20 years.6

After many years with little progress, increasedunderstanding, along with a certain amount ofserendipity, led to a raft of new treatments. The pa-tient journey really began to change in the late

1990s and early 2000s, when the myeloma treat-ment space saw the start of research into a numberof new active agents. The licensing of thalidomidein the USA in 2006, and in the UK in 2008, repre-sented a step change in the management ofmyeloma.31,36 Thalidomide affects cells signalling,influencing cellular processes such as growth anddivision.37 Subsequent modifications to this mole-cule have resulted in two drugs with similar modesof action: lenalidomide, used in combination withdexamethasone as a second-line treatment, and po-malidomide (also used in combination with dexam-ethasone), used for patients who have had at leasttwo prior treatments.37 Bortezomib, a proteasomeinhibitor, also interferes with signals that controlcell growth, inhibiting the breakdown of cellularproteins, which build up and cause the cells – par-ticularly cancer cells – to die.37 Bortezomib is par-ticularly useful for patients who require rapidreversal of renal dysfunction.38–41 Myeloma cells areparticularly sensitive to proteasome inhibition be-cause their primary function is to produce largeamounts of protein in the form of immunoglobulin.Combination therapy with these agents has alsobeen a major step forward.

About myeloma





Over the past ten years alone, ten new drugshave been approved in the USA for the treatment ofmyeloma (Cook G, personal communication, 2016).Translational research, combined with remarkableengagement in clinical research by patients, clini-cians and the pharmaceutical industry, will as-suredly open the door for more drugs to be added tothe armamentarium in the near future.

Our understanding of the genetics of myeloma isalso now much more comprehensive, with the recog-nition of mutations linked to less favourable out-comes. We also know that some patients respondwell to the thalidomide-based drugs, whereas othersdo not, but the reasons for this remain elusive. Fu-ture research into the recognised genetic differencesshould provide clues to underlying pathophysiolog-ical differences that result in such interpatient vari-ability in disease process and treatment response.This will be an important area to explore moving for-ward, as it is increasingly necessary to use new drugsin those patients who will benefit most. However,none of this has fully translated into clinical practiceyet and truly personalised medicine is still manyyears away.

‘We are now prolonging the lives of somany patients with multiple myeloma thatthey die of other causes’Graham Jackson,Consultant Haematologist, Newcastle uponTyne HospitalsAs patients with myeloma live longer and benefitfrom a better quality of life, healthcare professionalshave more opportunity to develop relationships withtheir patients. This has led to a change in clinicians’mind-sets – from a previously pessimistic attitudeabout myeloma, which was often seen as an unre-

warding therapy area, to a much more optimisticoutlook. This has a knock-on effect, with enthusiasticand interested clinical leads contributing to all aspectsof care, fostering enthusiasm and interest in the restof the team, which in turn raises levels of care.

Patients’ increased longevity, coupled with ouraging population, brings higher prevalence and thuslarger clinics, which has allowed larger hospitalsand specialist centres to run separate specialistmyeloma clinics staffed by clinicians with an inter-est in myeloma. In line with many other therapyareas in the modern NHS, multidisciplinary teamworking is essential. The inclusion of, for example,specialist nurses, radiologists, orthopaedic surgeonsand clinical oncologists brings different perspectivesto the management of patients, broadening theoverall care package.

Specialist nurses are playing an increasingly vitalrole in the management of patients with myelomaand taking the pressure off haematologists, withsome running nurse-led clinics, where they offer pa-tients a more holistic approach. In addition to pre-scribing, nurses direct patients to support groupsand other healthcare professionals, such as psychol-ogists, complementary therapists and social work-ers. Patients with myeloma generally require longerappointments than patients with other blood can-cers, owing to the numerous serious complicationsthey are often dealing with, including bone pain, andthe side effects of therapy, including neuropathy andinfection. Nurse-led clinics can often offer longertimeslots. Some clinics are also offering telephone-based follow-up, outreach clinics and homechemotherapy, taking further pressure off clinics.

In addition to new therapies that delay the onsetof complications, supportive care to manage symp-

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In the past ten years, ten new drugshave beenapproved bythe US FDA,which has tobe seen as a positiveCGordon Cook,

Consultant

Haematologist, University

of Leeds and Leeds

Teaching Hospitals

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toms when complications do develop is much im-proved, with the use of bisphosphonates to managebone disease a particularly notable milestone thathas made a big difference for myeloma patients.

The outlook for patients now is almostunrecognisable from 40 years ago… In the 1970s and 1980s, a diagnosis of myeloma was,in essence, an almost immediate death sentence,with the prospect of pain and a severely impairedquality of life until the patient’s death, which couldbe within weeks of diagnosis. The outlook for mostpatients is now almost unrecognisable, with longerlife expectancy, improved supportive care to managesymptoms and complications, treatment to delay de-velopment of complications (particularly in those di-agnosed earlier in the disease process), and theprospect of functional remission, with good qualityof life, albeit temporary, for many patients.

Forty years ago, patients with a diagnosis ofmyeloma would probably have never heard of thedisease, and would certainly have no access to infor-mation or support. Even now, most patients will nothave heard of myeloma when they are diagnosed;7

however, active patient organisations, charities, keyworkers (nurse specialists) and widespread internetaccess have transformed the landscape in terms ofsupport and information. Because of the amount ofinformation now available for myeloma patients, in-cluding ‘silver surfers’, most patients become very

knowledgeable about their disease and the availabletreatments after diagnosis, often acting as their ownadvocates, contributing to and questioning manage-ment plans and decisions. Patients can also get ad-ditional informal support from peers as they sharetheir experiences while waiting for appointments atmyeloma-specific clinics. This has particularlyhelped when clinicians are faced with treatmentchoices, recruitment to clinical trials and managingexpectations of patients during treatment of re-lapse/refractory stages of the disease. However,many of the much older patients do not have accessto information via the internet, so miss out on someof the benefits gained by those with access to a widersupport network. Older people are often also stilldeferential to healthcare professionals, followingtheir guidance unquestioningly, which may putthem at a disadvantage in clinics with healthcareprofessionals with a generalist background and nospecial interest in myeloma.

With the population affected by myeloma beingmarkedly older, there may have been a degree ofageism in the past, with treatment considered un-necessary or inappropriate for patients of advancedage. This is now a historic issue, with recognitionthat the decision to treat and the approach to use ac-tive treatments should be based on a patient’s levelof fitness and frailty, as much as numerical age. Themost important factor is to ensure a suitable balancebetween effective treatment and tolerability. The

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About myeloma





B

One size does not fitall, as multiplemyelomaaffectspatients ofdifferent agesand differentracial groups,with differentgenetics anddifferent drugresponsesCKarthik Ramasamy,

Consultant

Haematologist, Oxford

University Hospitals

availability of an elderly-care team has increased theopportunity for guidance on managing patients withco-morbidities and associated polypharmacy. The

importance of patient choice is also taken into ac-count, as patients of all ages, but most frequentlythose of advanced age, may choose to opt out ofmore aggressive treatment.

Work and research into the patient experienceby patient charities and professional groups has en-sured that many gaps in the patient journey and carepathway have been identified, and that the patientvoice is heard. However, there is still room for im-provement in terms of the black and minority ethnic(BME) community, whose voices are still missingfrom the agenda.

The advent of health policy has brought beneficial changes butcomplicated prescribing…42–44There was no real or perceived need for a health pol-icy in the 1970s and 1980s. Once a drug was licensed,physicians would prescribe it as they best saw fit forthe benefit of their patients. The introduction ofhealth policies in recent years has undoubtedly ledto beneficial changes, including minimum stan-dards, care pathways and measures to assure cost-effective use of limited NHS funds. However, this,combined with the high cost of newer treatments,has led to the need for payer approval to prescribedrugs based on health technology assessments(HTAs) undertaken by organisations such as NICE,the Scottish Medicines Commission (SMC) and AllWales Medicines Strategy Group (AWMSG), as wellas approved local formularies n

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Patientsalso needequitableaccess tosupportivecare andservices,includingorthopaedicsurgeons,palliative careand socialworkersCSarah Henshaw,

Myeloma Specialist

Nurse, Nottingham

University Hospitals

About myeloma





S Much has changed over the past 40 years owing to advances

in science and our increased understanding of myeloma, which

is reflected in changing patterns in the patient journey, clinical

care pathway and health policy

S Availability of a raft of new treatments over the past 20 years,

including thalidomide, lenalidomide, pomalidomide and

bortezomib, has transformed the patient journey

S Individual differences in genetics, disease course and treatment

response are recognised but the reasons remain elusive; this

has not yet translated into clinical practice

S Patients’ increased longevity, coupled with our ageing

population, brings higher prevalence and larger clinics,

facilitating specialist myeloma clinics

S Specialist nurses are playing an increasingly vital role in the

management of patients with myeloma, taking pressure off

haematologists and offering a more holistic approach

S Active patient organisations and charities and widespread

internet access have transformed the landscape in terms of

support and information, with most patients acting as their

own advocates

S Health policy has brought beneficial changes, aiming to level the

playing field for all patients, but licensed drugs now need to be

approved following health technology assessment

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Much still needs to be done to transfer our increasedknowledge about myeloma into changes in clinicalpractice. For example, our understanding of genet-ics and its effect on prognosis and treatment hastaken great leaps forward, but we are still some wayfrom aligning treatment with a patient’s personalgenetic archetype.

The welcome increase in survival combined withan ageing population means that more patients areliving well with myeloma than ever before and, al-though obviously remarkable and very positive, it hasresulted in an unrelenting increase in the size of clin-ics, which are struggling to offer the required capacity.Despite major improvements in survival, many pa-tients still die early in the disease course, probably dueto issues around early and timely recognition and di-agnosis of the disorder, and the side effects of therapy.Furthermore, there has been no plateau in survival,as illustrated by data from the USA (Figure 4).

The fact that most myeloma patients are >65years brings specific challenges. Many of these pa-tients, particularly those in the much older agegroups, are unsuitable for transplant or the currentcomplex and aggressive treatments, but still requireactive management that takes into account theirfrailty, co-morbidities and existing treatments. Fur-thermore, some newer therapies require infusionstaking as long as six hours which must be repeatedover many weeks. This is a daunting prospect forpatients of any age and puts further pressure on ca-pacity in day wards. More trials of new drugs androutes of administration are badly needed, but it canbe difficult to get trials off the ground owing to pro-hibitive costs, red tape and administrative issues.Important trials are often limited to a small numberof centres in limited geographical locations, whichmeans that patients may be denied the opportunityto participate.

Increasing constraints on the drugs that clini-cians can prescribe, to whom and at which point inthe disease course in the context of the rising costs ofdrugs and the lack of a value-based pricing ethosmean that access to treatment is another major issue.Many licensed drugs, which are available in countriessuch as the USA are denied to patients in the UK –based on HTAs and cost-effectiveness decisions thatare often made without input from patients who aredealing with the devastating effects of this disease orfrom those directly involved in their management.Advances have already been made in this respect, asCancer 52’s recent report on its assessment of patientinvolvement in the different HTA processes acknowl-edges that all HTA agencies are taking involvementof patient organisations seriously.47

Organisations such as NICE, SMC and AWMSGaim to provide a level playing field in terms of accessto drugs and technologies in the UK. NICE, particu-larly, is well-respected worldwide. However, recom-mendations based on HTAs, by their very nature,offer a broad brush stroke, with decisions made toachieve the best results for the typical patient acrossthe whole patient population and at an acceptablecost. The HTA process gives little or no considerationto the nuances of a disease as heterogeneous asmyeloma, for which varying epidemiological patternsand treatment responses require a more personalisedapproach, although increased patient organisation in-volvement should help in this regard.47 Furthermore,the HTA process is rigorous but also unwieldy, oftenresulting in delays of two or more years between adrug being legally licensed and being approved for usein the NHS. During this time, many myeloma patientsmay have missed out on a treatment that could haveprevented complications or even prolonged their life.The Cancer Drugs Fund (CDF) (Box 3), has been agreat resource, providing funding for drugs thatwould not otherwise have been routinely availablefrom NHS England. However, future treatment withthese drugs is now uncertain after the delisting ofmany cancer drugs, which means that new patientsmay not be able to start on drugs that can provide dis-ease and symptom control. Announcements made byNICE in February 2016 confirmed that they will over-see the CDF moving forward. The CDF will re-openfor new applications in July 2016, where all new can-cer drugs will be referred for appraisal. A recommen-dation for interim inclusion within the CDF for a drugwill only be made should a draft recommendation forroutine commissioning be issued or where there isuncertainty. Once marketing authorisation is ap-

| 11


About myeloma





3.Key ongoing issues in myeloma

Figure 4: Changes in survival from 1971–2010. Adapted from Kumar et al (2008)and Kumar et al (2012).45,46

1.0

0.8

0.6

0.4

0.2

0

0 20 40 60 10080 140120

Time (months)

Prop

ortio

n su

rviv

ing

1971–1976 1977–1982 1983–1988 1989–1994

1995–2000 2001–2006 2006–2010

$For further information

see the following report:

Speaking up for patients –

Patient organisation

involvement in Health

Technology Assessment

(HTA) with a focus on

Patient and Clinical

Engagement (PACE) at

the Scottish Medicines

Consortium (SMC) report

proved, NICE generally look to issue final guidancewithin 90 days. From this point, if the drug is recom-mended it will enter into the current commissioningpathway; however, any drug recommended for ongo-ing entry into the CDF will be discussed by a jointNHS England and NICE CDF Investment Group toagree commercial access and timeframes for reviewof its inclusion in the CDF, where the drug will be re-appraised by NICE for routine commissioning.48

The new NICE guideline NG35, Myeloma: diag-nosis and management, aims to raise standardsacross the country.35 They predominantly encompassdiagnosis, monitoring and supportive management.Unlike technology appraisals, recommendations donot oblige providers to implement the guidance andfunding does not automatically follow. Recommen-dations may also be difficult to immediately achievein practice, as imaging services do not have the ca-pacity to offer MRI for every patient with suspectedmyeloma,11 particularly when scanners are needed todiagnose other urgent conditions, such as emboli,risking breach of waiting and referral times. Clinicalreference groups were intended to develop spe-cialised service contracts and were tasked with ensuring service specifications and clinical commis-sioning policies were delivered on time and to a highstandard,50 but it can take years to develop treatmentalgorithms – which are already out of date oncelaunched – and there is no mandatory requirementto follow them. Access to drugs is not the only equityissue, as patients also need equitable access to sup-portive care and services, including orthopaedic sur-geons, palliative care and social workers.

Education and awareness are critical to the suc-cessful diagnosis and management of myeloma. GPsand other generalist healthcare professionals dealwith the whole spectrum of diseases. With myelomabeing so rare, many physicians will only see one ortwo cases – if any – throughout their career, so it isnot high on the list of priorities for initial or contin-

uing education. Therefore, it is not entirely surpris-ing that diagnosis remains late in the course of thedisease. Although the amount of information avail-able for patients has increased dramatically in recentyears, with positive impacts on the patient journey,much does not target those most at risk. Given theproportion of black people affected by myeloma, in-formation is often not culturally appropriate anddoes not reflect the current diversity of the UK pop-ulation (Box 4) n

12 |






B

We are still some way awayfrom trulyadjustingtreatmentbased ongeneticfactorsCMatthew Jenner,

Consultant

Haematologist,

University Hospital

Southampton

Box 4: Issues around minorities in myeloma.• Black African and Caribbean people have a higher risk of developing

myeloma, are often diagnosed at a younger age, and have twice themortality.14 There are further inequalities along the social class gradient, with disadvantaged groups having poorer outcomes.51

• The Basil Skyers Myeloma Foundation is a voluntary organisation established in 2010 to provide practical support and resources for patients,their families and carers.

• Important priorities for the foundation are to campaign for diversity to bewoven into the fabric of clinical research, and to raise awareness amongpolicy makers, clinicians, the wider research community and those who planand deliver public services about the importance of understanding thediversity of patients with myeloma. This understanding is absolutelyfundamental to informing a broader and more accurate picture of patients asindividuals; subsequently tailoring services and support in a way thatenhances health outcomes for all.

• In 2015, the campaigning efforts of the foundation and its research wererecognised nationally by Duncan Selbie, Chief Executive of Public HealthEngland and the National Cancer Intelligence Network, and Sean Duffy,National Clinical Director for Cancer. Both have pledged their ongoingsupport for the foundation and for integration of equality into the myelomapolicy discourse and practice. Lord Morris of Handsworth has also pledged tochampion this agenda and to continue to raise awareness of the broadspectrum of equality issues as they relate to myeloma.

Sophia Skyers, Chair, Basil Skyers Myeloma Foundation

S The advanced age of patients with

myeloma brings challenges in terms of

treatment options for differing frailties,

co-morbidities and polypharmacy

S Despite major improvements in

survival, many patients still die early

in the disease course, and there has

been no plateau in survival

S Much of the available educational

information does not reflect the diversity

of the UK population, and does not

target those at highest risk, particularly

black people

S Modern health policy means that

access to newer expensive licensed

drugs may be limited, with delisting of

agents from the Cancer Drug Fund

creating uncertainty for many patients

Box 3: What is the Cancer DrugsFund (CDF)?48,49

• Established in 2010 by the NHS England Clinical Reference Group for Chemotherapy inconjunction with local clinical leads

• Allows eligible cancer patients to access drugsthrough the NHS that otherwise would not beavailable to them

• Patients must fall within the specific requirementsset out within the CDF to be considered forreceiving the medication

• As of July 2016, NICE will oversee the drugs that will enter onto the CDF. Each new drug will be appraised by NICE and will only feature in the CDF if a draft recommendation for routine commissioning is issued or where there is uncertainty

The lives of many patients with myeloma are alreadybeing prolonged so that they die of other causes, butwe can still build on the advances achieved to dateby tackling the ongoing issues outlined earlier. Withan aspirational eye, further innovations that fallunder three key themes might be achieved:ğDiagnose myeloma early, before it has caused

damage to the bone, bone marrow function andkidneys

ğ Improve available treatment options and developa cure for myeloma

ğ Ensure equity of access to treatments for patientswith myeloma.

‘The key is to diagnose multiple myelomabefore it has damaged the bone andkidneys’ Graham Jackson, ConsultantHaematologist, Newcastle upon Tyne HospitalsBecause myeloma is more likely than other cancers,on average, to present first as an emergency (34%for myeloma versus 22% for all malignant neo-plasms, excluding non-melanoma skin cancer19,20),approaches to diagnosing myeloma earlier, espe-cially before bone and renal complications have de-veloped, are crucial.

The current diagnostic tests are simple and ade-quate, but they are of no use if the disease is not sus-pected and those tests are not ordered. Therefore,increased education is needed to raise awarenessand suspicion of myeloma among healthcare profes-sionals, including general haematologists and GPs.This education might take the form of booklets andelectronic training, but with clinicians already over-whelmed by the amount of information that appearson their desks and in their inboxes, including edu-cation and awareness campaigns, any training needsto be part of a formal continuing professional devel-opment programme to encourage participation.Some units have found it useful for haematologiststo provide face-to-face educational sessions for GPs,and consultants may also provide advice by tele-phone or email.

Screening is another potential approach to in-crease earlier diagnosis; however, it is a controver-sial subject. Identification of MGUS would allowclose monitoring of patients before they becomesymptomatic, but because few cases of MGUSprogress to myeloma, many patients might have todeal unnecessarily with the psychological aspects ofthis potentially devastating diagnosis. However, re-search into screening is certainly warranted to de-termine the balance between early identification andtreatment, and the psychological impact for patientswho’s MGUS may never progress.

A cure for myeloma is the Holy Grail and, with the accomplishments of recentdecades, it seems entirely achievable,albeit still some way off…Although the search for a cure continues, further ad-vances in disease control and symptomatic manage-ment are perhaps more realistic aspirations for thenext decade.

It is increasingly apparent that every patient’smultiple myeloma is different and one size does notfit all. Moving forward, research is needed to eluci-date not just the biology of the disease, which is stillinsufficiently understood (for example, we know thatsome cases of MGUS transform to myeloma,whereas others do not, but not why this is the case).Research into the biology of the host is also neededto understand why treatments are only effective insome patients and why not everyone develops sideeffects. Therefore, further scientific work is neededto fully elucidate the genetics of the disease and todetermine how to translate that into clinical practiceso we can optimise the use of the currently availabletreatment options. The ultimate goal is personalisedmedicine, where the treatment is truly tailored toevery individual patient based on genetics, biomark-ers of the host immune system, and to take accountof co-morbidities and frailty, especially in elderly pa-tients. To achieve this, we need to build on thehealthy UK clinical trials environment (which is al-ready impacting on clinical practice in the UK andbeyond as research findings are incorporated intonational guidelines) by actively recruiting patientsinto clinical trials with sufficient participants toallow stratification into subgroups.

Research must seek to not only find new treat-ments to improve disease control but also managethe complications and side effects of disease and op-timise delivery methods. For example, although thebisphosphonates have been a game-changer when itcomes to halting progression of bone disease inmyeloma patients, the next step is reversal of bonedisease, and this should be the focus of some re-search efforts. Furthermore, research needs to in-vestigate new administration routes, which willimprove patient convenience and comfort, and helpreduce the additional pressure these infusions puton capacity in clinics.

With the range of symptoms and complications,and the disease’s impact on life expectancy and qual-ity of life, myeloma patients benefit from a holisticapproach to management. Every patient should haveaccess to the full range of specialist support, includ-ing psychologists, complementary therapists, pallia-tive care and social workers (Box 5). Ideally, every

| 13


About myeloma





4. Visions for myeloma 2025

$Leukaemia care have

designed an e-learning

course specifically for

GPs to improve their

awareness and knowledge

of blood cancers in

conjunction with the

Royal College of General

Practitioners (RCGP)

for further information

see the RCGP website

$For further information see

the following guidelines:

British Committee for

Standards in Haematology

and UK Myeloma Forum

• ESMO clinical practice

guidelines for diagnosis,

treatment and follow-up

of myeloma

• International Myeloma

Foundation

• Nice myeloma

guidelines NG35

hospital would have a Maggie’s Centre or similar onsite. At Nottingham University Hospital, the highestrate of psychological referrals are for patients with arelapse of symptomatic myeloma, with the first re-lapse often hardest to deal with (Henshaw S, per-sonal communication, 2016). Therefore, patientsneed support with the psychological impact of theirdiagnosis and to navigate other unexpected obsta-cles. For example, many patients with myeloma arerefused travel insurance because they are on ‘cancerchemotherapy’, which is assumed to mean they areunfit to travel or likely to encounter expensive med-ical costs should they fall ill abroad, even thoughtheir myeloma is likely to be stable for several years.

‘We need to see new strategies that willreduce the time between licensing andeconomic approval to use drugs’ GordonCook, Consultant Haematologist, University ofLeeds and Leeds Teaching HospitalsEquity of access covers a whole gamut of issues, in-cluding age, race, and health policy and economics.

Elderly patients have complex needs and requirea broader range of treatment options – not as com-plex or aggressive as triplet or quadruplet therapy –and with doses adjusted to consider their frailty, co-morbidities and existing medications. However, com-plex elderly patients are often excluded from trials asthey fail to meet the inclusion criteria. Also, relativelyfew centres participate in the limited trials that areunder way so it can be difficult for patients to enrolbecause of issues concerning logistics and travel.Therefore, future clinical trials need broader inclusioncriteria to ensure enrolment of more of the complexelderly patients who are predominantly affected bymyeloma. More trial sites will also be required – ormore flexible arrangements for monitoring in clinicaltrial protocols – to make it easier and more attractivefor older patients to participate.

Future research needs to reflect that black peopleare at least twice as likely to be diagnosed withmyeloma as white people. Future trials need to en-courage greater participation by black people, whichmay require changes in recruitment strategies andcommunication tools so that they are culturally ap-propriate. Stratification of the results by race willalso be needed, which will be beneficial for disentan-gling some of the questions around the impact of ge-netics and race on epidemiology and treatmentresponse. Results of datasets such as hospitalepisode statistics should also be stratified by race.

No matter how many new treatments the re-search community develop, those treatments areworthless if clinicians cannot prescribe them to pa-tients. To tackle this problem requires both changesin health policy and more affordable pricing strategiesfrom the pharmaceutical industry. We need to see

new strategies that will reduce the time between li-censing and economic approval to use drugs. The pro-posed changes to the CDF may impact upon this.Further strategies might also involve including HTAbodies in the development of clinical trial protocols,so that we are certain that the data we are creatingtally with the data needed to make health-economicdecisions, much as the European Medicines Agencyinforms the development of clinical trials from a reg-ulatory perspective. HTA bodies might also begin re-viewing the evidence ahead of licence approval, sothat the work and time required post-licence is min-imised. Furthermore, experts in myeloma, includingpatients themselves, need to be fully involved in theHTA process, so that decisions are informed by directexperience with patients dealing with this devastatingdisease. Regional variation in access to treatments isanother issue. Formerly, drugs were often availablein England but not Scotland or Wales; however, thissituation has reversed for some drugs as they havebeen delisted by the CDF in England.49 Wider aware-

14 |






Box 6: What is the PharmaceuticalPrice Regulation Scheme (PPRS)?• Voluntary agreement between the Department of

Health (DH) and the pharmaceutical industry52

• Aims to provide effective medicines to the NHS ata reasonable cost53

• Encourages a strong, efficient and profitablepharmaceutical industry53

• Began in 1957 and renews on average every five years53

• If the NHS overspend on branded medicines inexcess of the growth rate set out by the scheme,the pharmaceutical company is required to makepayments to the DH52

Box 5: Provision of supportive services to myeloma patients.• At Nottingham University Hospital (NUH), we have managed to secure

funding for a clinical psychologist, a complementary therapist and anoutreach service to enable all patients to have treatment in the home. Theoverall impact for patients has been vast and helps both them and theirfamilies to cope with the disease.

• Initially recruited through funding from the Kay Kendall Charity, the clinical psychologist has proven so successful that the post is now funded by the trust. The psychologist has been extremely beneficial for patients and their families.

• Some of the overall cost of the complementary therapist has been supportedby The Basil Skyers Myeloma Foundation; however, the role is predominantlyfunded by the NUH Charities. The complementary therapy has not onlyhelped with pain and symptom management but also aids relaxation, whichmeans that patients can learn how to cope living with a long-term illness.

• Another important service, starting in March 2016, is the HaematologyOutreach Service, also funded by the Kay Kendall Charity. This will impact onthe patient experience, as patients will be able to have chemotherapy in theirown homes. We envisage that this will be more convenient for patients andreduce transport problems.

Sarah Henshaw, Myeloma Specialist Nurse, Nottingham University Hospitals

B

Myeloma robs people of theirfuture –asthey can’tplanCJohn Ashcroft,

Consultant

Haematologist,

Mid-Yorkshire Hospitals

$For further information

see the following reports:

• Listen up! Multiple

myeloma in black

communities: an

unequal risk burden.

• Multiple myeloma in

black communities:

addressing inequalities

ness of the Pharmaceutical Price Regulation Scheme(Box 6),52 which provides assurance on the bill for al-most all branded medicines for the NHS through avoluntary agreement between the pharmaceutical in-dustry, is also needed, so that more clinicians canmake the case to prescribe the newer, more expensivetreatments with their regional funding bodies nReferences

1. National Cancer Intelligence Network. Trends in incidence and outcome forhaematological cancers in England: 2001–2010. London: 2014. 2. Cancer Research UK. About myeloma. http://www.cancerresearchuk.org/about-cancer/type/myeloma/about/ (last accessed 11 January 2016)3. NHS Choices. Multiple myeloma. 2015. 4. Landgren O, Kyle RA, Pfeiffer RM et al. Monoclonal gammopathy of unde-termined significance (MGUS) consistently precedes multiple myeloma: aprospective study. Blood 2009; 113: 5412–5417.5. Landgren O, Weiss BM. Patterns of monoclonal gammopathy of undeter-mined significance and multiple myeloma in various ethnic/racial groups: sup-port for genetic factors in pathogenesis. Leukemia 2009; 23: 1691–1697.6. Bird JM, Owen RG, D’Sa S et al. Guidelines for the diagnosis and manage-ment of multiple myeloma 2014. London: 2014. 7. National Collaborating Centre for Cancer. Myeloma in adults: diagnosis andmanagement – draft guideline. London: 2015. 8. Kyle RA, Rajkumar SV. Criteria for diagnosis, staging, risk stratification andresponse assessment of multiple myeloma. Leukemia 2009; 23: 3–9.9. Rajkumar SV, Landgren O, Mateos M-V. Smoldering multiple myeloma.Blood 2015; 125: 3069–3075.10. Ludwig H, Miguel JS, Dimopoulos MA et al. International Myeloma WorkingGroup recommendations for global myeloma care. Leukemia 2014; 28:981–992.11. National Institute for Health and Care Excellence. Metastatic spinal cordcompression in adults: diagnosis and management. NICE clinical guideline 75.London: 2008. 12. Cancer Research UK. Myeloma statistics. http://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma#heading-Zero (last accessed 11 January 2016)13. Cancer Research UK. Myeloma incidence statistics. http://www.cancerre-searchuk.org/health-professional/myeloma-incidence-statistics#heading-One(last accessed 10 March 2016)14. Basil Skyers Myeloma Foundation. Listen up! Multiple myeloma in blackcommunities: an unequal risk burden. 2015. 15. King AJ, Gooding S, Ramasamy K. Managing multiple myeloma in the over70s: A review. Maturitas 80: 148–154.16. Ludwig H, Durie BGM, Bolejack V et al. Myeloma in patients younger thanage 50 years presents with more favorable features and shows better survival:an analysis of 10 549 patients from the International Myeloma Working Group.Blood 2008; 111: 4039–4047.17. Cancer Research UK. Myeloma risk factors. http://www.cancerre-searchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma#heading-Zero (last accessed 11 January 2016)18. Cancer Research UK. Myeloma survival statistics. http://www.cancerre-searchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/myeloma#heading-Zero (last accessed 18 January 2016)19. Public Health England. Routes to diagnosis 2006-2013 workbook. London:2015. 20. Cancer Research UK. Myeloma diagnosis and treatment statistics.http://www.cancerresearchuk.org/health-professional/cancer-statistics/statis-tics-by-cancer-type/myeloma/diagnosis-and-treatment#heading-Three (lastaccessed 11 January 2016)21. Myeloma UK. How is myeloma treated?22. Inhye E. Ahn SM, Neha Korde, and Ola Landgren. Dilemmas in treatingsmoldering multiple myeloma. J Clin Oncol 2015; 33: 115–123.23. Ludwig H, Sonneveld P, Davies F et al. European perspective on multiplemyeloma treatment strategies in 2014. Oncologist 2014; 19: 829–844.24. Durie BG, Kyle RA, Belch A et al. Myeloma management guidelines: a con-sensus report from the Scientific Advisors of the International Myeloma Foun-dation. Hematol J 2003; 4: 379–398.25. Janssen-Cilag Ltd. Velcade 3.5mg powder for solution for injection: sum-mary of product characteristics. High Wycombe: 2016. 26. Sandoz Limited. Cyclophosphamide 1000 mg powder for solution for in-jection or infusion: summary of product characteristics. Camberley: 2014. 27. Focus Pharmaceuticals Ltd. Dexamethasone 10mg/5ml oral solution: sum-mary of product characteristics. London: 2015. 28. Janssen-Cilag Ltd. Caelyx 2mg/ml concentrate for solution for infusion:summary of product characteristics. High Wycombe: 2015. 29. Aspen Pharma Trading Limited. Melphalan 2 mg tablets: summary of prod-uct characteristics. Dublin: 2014. 30. Alliance Pharmaceuticals Limited. Deltacortril 5mg gastro-resistant tablets:summary of product characteristics. Chippenham: 2014. 31. Celgene Europe. Thalidomide Celgene 50 mg hard capsules: summary ofproduct characteristics. Uxbridge: 2015. https://www.medicines.org.uk/emc/medicine/21005 (last accessed 21 January 2016)32. Celgene Ltd. Imnovid 1 mg: summary of product characteristics. Uxbridge:2015. 33. Myeloma UK. NCRI Myeloma X trial shows benefit of second-high dosetherapy and autologist stem cell transplantation in relapsed myeloma, 2014.34. Snowden JA, Ahmedzai SH, Ashcroft J et al. Guidelines for supportive carein multiple myeloma 2011. Br J Haematol 2011; 154: 76–103.35. National Institute for Health and Care Excellence. Myeloma: diagnosis andmanagement. London: 2016. 36. US Department of Health and Human Services. Drug details: Thalomid.Washington, DC, USA: 2006. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm?fuseaction=Search.Overview&DrugName=THALOMID(last accessed 21 January 2016)37. Cancer Research UK. Biological therapy for myeloma. http://www.cancer-researchuk.org/about-cancer/type/myeloma/treatment/biological-therapy-for-myeloma (last accessed 21 January 2016)38. Chanan-Khan AA, Kaufman JL, Mehta J et al. Activity and safety of borte-zomib in multiple myeloma patients with advanced renal failure: a multicenter

retrospective study. Blood 2007; 109: 2604–2606.39. Dimopoulos MA, Terpos E, Chanan-Khan A et al. Renal impairment in pa-tients with multiple myeloma: A consensus statement on behalf of the Inter-national Myeloma Working Group. Journal of Clinical Oncology 2010; 28:4976–4984.40. Chanan-Khan AA, San Miguel JF, Jagannath S, Ludwig H, DimopoulosMA. Novel Therapeutic Agents for the Management of Patients with MultipleMyeloma and Renal Impairment. Clinical Cancer Research 2012; 18:2145–2163.41. Qayum A, Aleem A, Al Diab A, Niaz F, Al Momen AK. Rapid improvementin renal function in patients with multiple myeloma and renal failure treated withbortezomib. Saudi J Kidney Dis Transpl 2010; 21: 63–68.42. Independent Cancer Taskforce. Achieving world-class cancer outcomes:a strategy for England 2015–2020. London: 2015. 43. Department of Health. Improving outcomes: a strategy for cancer: fourthannual report. London: 2014. 44. Department of Health. Cancer reform strategy. London: 2007. 45. Kumar SK, Dispenzieri A, Lacy MQ et al. Continued improvement in survivalin multiple myeloma: changes in early mortality and outcomes in older patients.Leukemia 2014; 28: 1122–1128.46. Kumar S, Dispenzieri A, Gertz M et al. Continued improvement in survivalin multiple myeloma and the impact of novel agents. 54th Annual Meeting ofthe American Society of Hematology, Atlanta, USA, 2012 (Poster)http://myeloma.org/pdfs/ASH2012_Kumar_3865.pdf (last accessed 31 March2016)47. Cancer 52. Speaking up for patients: patient organisation involvement inhealth technology assessment, with a focus on patient and clinical engagementat the Scottish Medicines Consortium. London: 2015. 48. Selina M. NHS England approves Cancer Drugs Fund plans.http://www.pharmatimes.com/Article/16-02-25/NHS_England_approves_Can-cer_Drugs_Fund_plans.aspx (last accessed 9 March 2016)49. NHS England. The Cancer Drugs Fund. London: https://www.england.nhs.uk/ourwork/cancer/cdf/ (last accessed 5 February 2016)50. NHS Commissioning Board. Clinical reference groups for specialised serv-ices: a guide for clinicians. 2013. 51. Gómez LE, López N. Mapping “race”: critical approaches to health dispar-ities research. New Brunswick, NJ: Rutgers University Press, 52. Department of Health. The pharmaceutical price regulation scheme 2014.London: 2013. https://www.gov.uk/government/publications/pharmaceutical-price-regulation-scheme-2014 (last accessed 5 February 2016)53. Association of the British Pharmaceutical Industry. Understanding the Phar-maceutical Price Regulation Scheme (PPRS). 2014. http://www.abpi.org.uk/our-work/commercial/pprs/Pages/default.aspx (last accessed 5 February2016)

| 15


About myeloma





S With myeloma more likely to first present as an emergency

compared to other cancers; approaches to diagnose myeloma

earlier, particularly before bone and renal complications have

developed, are crucial

S Increased education is needed to raise awareness and

suspicion of multiple myeloma among healthcare professionals,

including general haematologists and GPs

S Research into screening is certainly warranted to determine the

balance between earlier identification and treatment, and

worrying patients who are otherwise well

S Research is needed to elucidate the biology of not just the

disease but also the host, to understand why treatments are

effective in only some patients and why only some develop

side effects

S Research must seek to not only find new treatments to improve

disease control but also to manage the complications and side

effects of disease and optimise delivery methods

S Patients with multiple myeloma benefit from a holistic approach

to management; every patient should have access to the full

range of specialist support, including psychologists,

complementary therapists, palliative care and social workers

S Future clinical trials need to have broader inclusion criteria that

allow enrolment of more complex elderly patients, who are

predominantly affected by myeloma, and more trial sites to

make participation easier

S Future research needs to reflect the fact that black people

are at least twice as likely to be diagnosed with myeloma as

white people

Diagnose myeloma early, before it has caused damage to the bone, bone marrow function and kidneys

Ensure equity of access to treatments for patients with myeloma

Improve available treatment options and develop a cure for myeloma

Further advances in disease controland symptomatic

management

Inclusion of morecomplex elderly

patients within trial

Increased education for healthcare professionals

across primary andsecondary care

Access to bloodtests and imaging,which can facilitate

early diagnosis. This remains a challenge

due to lack of capacityand failure torecognise the

disease

Research intounderstanding

the balance betweenearly screening forMGUS in patients

and the psychologicalimpact of this

diagnosis

Research isneeded to fullyunderstand thebiology of the

disease

Stratification of bothtrial results and hospital

episode statistics byrace will be required tounderstand the role of

genetics and racetreatment response

More trial sites, ormore flexible arrangements

for monitoring in protocols, are needed to make it easier forolder patients to participate

Research intothe biology of thehost is required in

order to understandwhy some treatmentsare only effective in

specific patients,and why onlysome developside effects

Future trials needto include greater

proportions ofblack people

Build on the healthyclinical trials environmentin the UK to recruit morepatients and categorise

them into relevantsubgroups

The reversalof bone disease

should be afocus of ongoing

research

Every patient shouldhave access to the

full range of specialistsupport, including

psychologists,complementary

therapists, palliativecare and social

workers

We need to fullyunderstand thegenetics of the

disease anddetermine how to

translate this knowledge intoclinical practice

Research mustfind new treatmentsto improve disease

control, and manage thecomplications and side effects of the

disease

We need to see newstrategies that will reduce thetime between licensing and

economic approvalto use drugs

Determinenew administration

routes for current agentswith long infusion times, to

improve patient convenienceand help reduce

additional pressure onclinic capacity

Changes in healthpolicy are urgently needed

to ensure treatmentsdeveloped by the researchcommunity can actually

be prescribedto patients

HTA bodies couldbe involved with the

development of clinicaltrial protocols or beginreviewing the evidence

ahead of licenceauthorisation

Experts in and patientswith myeloma need to

be fully involved inthe HTA process

Regional variationsin access to

treatment needsto addressed

Wider awareness of thePharmaceutical Price Regulation

Scheme, which provides assurance on the bill for almost all branded

medicines for the NHS is required

Visions formyeloma

2025

Salvage kidneyfunction to ensure all

treatment options whenthey relapse can

be accessed

Call to action points

Date of preparation: March 2016, Job code: UKIE-CC-NPS-0216-124622 COVER IMAGES: EYERETINA/VECTOR ICONS/SHUTTERSTOCK

Diagnose myeloma early, before it has caused damage to the bone, bone marrow function and kidneys

Documents

State of the nation in multiple myeloma – a UK perspective