The challenges of managing myeloma
in the elderly
Stella Bowcock November 2013
The UK population is aging
• 80+ are currently 3 million
• Predicted to be nearly 6 million by 2030
Definition of Elderly?
1. Age ≤ 65
•
Eligible for asct (autologous stem cell transplant)
2. Age 65-75
•
May or may not be eligible for asct
3. Age ≥ 75
•
Not eligible for asct
Talk today mostly about category 3
Epidemiology of Myeloma
Myeloma is a disease of the elderly
Incidence according to age
• In UK median age at diagnosis 73 (1990s)
• Latest USA SEER registry data: 55% are ≥ age 75 (19752010)
• Incidence and prevalence of myeloma expected to rise
– Aging population
• predicted increased incidence of 57% between 2010-2030
– Improved survival with novel therapies
• therefore increased prevalence
Age-specific incidence rates by age group for myeloma in males
and females
between 2006-2008 in England
NCIN. Haematological malignancies in England 2001-2008
Myeloma survival in England according to age
NCIN. Courtesy
Hamish Ross
Why such a high early death rate?
Early deaths age >75: (Rodon et al, 2001 and Bang et
al, 2013)
• Infection rate high
• Not treated -(comorbidity, poor PS, very old
age, patient refusal)
• Drop out from treatment (mostly toxicity)
• Delayed diagnosis?
Rodon et al. Multiple myeloma in elderly patients: presenting features and outcome. Eur J Haematol. 2001:66:11-17
Bang et al. Treatment patterns and outcomes in elderly patient with multiple myeloma. Luekemia. 2013:27:971-974
Is the disease more aggressive in older patients?
No
Disease presentation at a later stage?
Yes
Can we improve early mortality?
• Infection
– TEAMM trial (Tackling EArly Mortality and
Morbidity in Myeloma)
– Important question in elderly
TEAMM
Eligibility
• Newly diagnosed symptomatic myeloma
• Intention to give anti-myeloma therapy
• Want to include the elderly and frail
Levofloxacin for 12 weeks
(n=400)
Placebo for 12 weeks
(n=400)
Benefits
Risks
Assess number of febrile episodes plus
• Deaths <12 wks
• Days in hospital <12 wks
• Myeloma response
• Survival and QOL
Healthcare associated infections
• 4 weekly nasal swabs & stools
• Invasive infections
Do elderly patients want treatment?
• Majority do
• Emphasis on quality of life (QoL) vs increased
survival
• Dependent upon the attitude of the physician
How does treatment affect QoL?
• Haematologists slow to include QoL in trials
• 1990s solid tumour trials included QoL
– Less chemoresponsive than Haematological
malignancies
• Results consistently showed that, provided the
tumour is responding, QoL is better on
chemotherapy than no treatment
QoL studies in myeloma
• QoL is worse when disease activity is high
• QoL improves as the disease comes under control
– Physical aspects of QoL especially pain and fatigue
• If the aim is QoL, trial of treatment is likely to be
beneficial
Summary so far
• Dreadful early mortality in the elderly
– Need to try to improve on it
• Majority of elderly patients do want treatment
• Responses to treatment are associated with improved QoL
• Myeloma is a highly treatable cancer
We need very good reasons NOT to offer treatment to
elderly patients
Questions when faced with a newly
diagnosed elderly patient
– Are they likely to benefit from treatment?
– How can I assess the patient?
– How much is reversible due to myeloma and how much
pre existing?
– How can I predict toxicity?
– How can I modify treatment and supportive care to gain
maximum efficacy without toxicity?
Normal aging
• Progressive decline in all
physiological systems with
age
• After ~age 75 our systems are
less able to compensate for
insult
• Frailty –minor insult may lead
to disproportionate
deterioration in health
Figure 1 Vulnerability of frail elderly people to a sudden change in health status after a minor illness
Andrew Clegg , John Young , Steve Iliffe , Marcel Olde Rikkert , Kenneth Rockwood
Frailty in elderly people
The Lancet Volume 381, Issue 9868 2013 752 - 762
http://dx.doi.org/10.1016/S0140-6736(12)62167-9
Measures of Frailty
• Phenotype model (Fried et al)
– ≥3 of
• weakness, poor endurance, weight loss, low physical
activity, slow gait speed
• Cumulative deficit model (frailty index Rockwood et al)
– 92 variables
• symptoms, signs, lab values, disease states, disability
Fried et al, Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001;56:M146-156
Rockwood et al, A global clinical measure of fitness and frailty in elderly people. CMAJ 2005;173:489-495
Assessment
Comorbidity
Functional assessment
Tools
Charlson comorbidity index
(CCI)
Tools
Multiple different
assessment tools
Cumulative index rating scalegeriatric(CIRS-G)
Comprehensive geriatric
assessment -gold
standard
Which patients do not benefit from
treatment?
Comorbidity
• Unlikely to benefit if severe life threatening
comorbidity eg CIRS-G score 4
– Extremely severe/ end organ failure
• Patients with score 1, 2 and probably 3 should
be offered treatment
– Exceptions eg dementia
– Need to tailor treatment according to comorbidity
Which patients do not benefit from treatment?
(2)
Frailty
Overall QOL improves as disease comes under control
BUT some severely frail patients may not benefit
Pragmatic patient assessment
Frailty grade
Description
Fit/ moderately fit
Active
Limited activity but
independent
Need help for household
Mildly frail
tasks eg shopping, finances
(IADL)
Partial help for personal care
Moderately frail
eg dressing, bathing,
toileting (ADL)
Severely frail (NOT poor Completely dependent for
personal care (ADL)
PS due to myeloma)
Vulnerable
Is the poor performance status
reversible?
• Very dependent on the patient and carer
history
• In QoL studies physical and fatigue aspects
may be reversible
• Psychosocial issues may be more important
than physical ones for prognosis
How can I predict toxicity?
• Older age
• Full dose chemotherapy
• Abnormal laboratory values eg Hb, albumin,
creatinine
– Mostly due to high disease activity/burden
• Geriatric assessment
–
–
–
–
Inability to walk one block
Falls
Requires support with taking medication
Decreased social activity
Hurria et al, J Clin Oncol.2011;29(25):3457-6. Predicting chemotherapy toxicity in older adults with cancer: a prospective
multicenter study
Extermann M et al, Predicting the risk of chemotherapy toxicity in older patients: the Chemotherapy Risk Assessment
Scale for High-Age Patients (CRASH) score. Cancer.2012;118(13):3377-86
How can I modify treatment to
avoid toxicity?
• Dose reduce, especially in first 1-2 cycles
– Complication and toxicity rate highest when
disease burden/activity is highest
– Retrospective analyses shows some patients drop
out early due to toxicity
– Treatment interruptions associated with poorer
outcome
How much to dose reduce?
Risk factors
1. Age >75
2. Mild, moderate or severe frailty
3. Comorbidities; cardiac, pulmonary, hepatic, renal
none
Standard
dose
one
Dose level -1
~75%
≥2*
Dose level -2
~50% dose*
Modified from Palumbo et al, Personalised therapy in multiple myeloma according to patient age and vulnerability. Blood 2011;118:4519-1529
*Peyrade et al, Attenuated immunochemotherapy regimen (R-miniCHOP) in elderly patients older than 80 years with diffuse large B cell lymphoma.
Lancet Oncol 2011;12:460-468
Avoiding toxicity
•
•
•
•
Dose reduction
Patients want QoL rather than survival
Increase the dose if well tolerated
Toxicity assessment after each cycle
Supportive care
• Most important in elderly
– Medical aspects eg.
• High infection rate, higher rate herpes zoster,
thromboembolism
• Psychosocial support
• Need the help of the geriatricians
Future Research
• Improve on early mortality
• Improve on QoL data
• Which patients are unlikely to benefit from
treatment
• Appropriate dose reductions
• Supportive care
Summary
• Myeloma in the frail elderly is becoming commoner
• High early mortality in the elderly
• Most elderly patients want treatment provided they
have good QoL
• Functional assessment in oncology is still evolving
• Toxicity can be reduced with dose reduction
• Meticulous supportive care is probably important
Conclusion
Elderly patients live on the borderline of a
precariously balanced physiological state.
Attention to detail in ALL aspects of the patient’s
care is likely to produce the best outcome