IV EAFO Hematology Forum, 2016, St. Petersburg

1. QUALITY OF LIFE ISSUES IMPORTANT TO
PATIENTS WITH HEMATOLOGICAL
MALIGNANCIES
Hematology Unit - Azienda Ospedaliera B-M-M
Reggio Calabria, Italy
Esther N Oliva

2. Contents
Treatment and Adherence
Quality of life issues important to patients with
hematological malignancies
EHA SWG project
Burden of Hematological Malignancy
Conclusions

3. PROs: Indicators for assessing impact of disease
and treatment.
PROs include quality of life (QoL) + symptoms obtained
directly from patients
 QoL is a complex multidomain and variable construct that represents
the patient’s overall perception of the impact of an illness and its
treatment1,2
A symptom is any subjective evidence of a disease, health condition,
or treatment-related effect that can be noticed and recognized only by
the patient3,4
1Bowling A, 1996; 2Gorodokin G and Novik A, 2005, 3Trotti A, 2007; 4Spivak JL,2009 ;
5Passik SD, 1998; 6Fallowfield L, 2001;
Physicians vary in their ability to elicit PROs5,6

4. Velikova G, 2002; Acquadro C, 2003
PROs in daily practice: facilitation of communication
1. Indicator for assessing impact of disease.
PROS and other data gathered
 During history taking
 During follow-up
 accurate medical diagnosis, and choice of treatment.
2. Indicator for assessing treatment efficacy.
 Symptoms/Side effects only through PROS
 Impact of treatment on functioning and well-being.
3. Useful for interpreting clinical outcomes (prognosis).
 Efficacy
 Survival.
4. A key element in treatment decision making.

5. What do patients with hematological malignancies have in
common in terms of disease burden?
Quality of life
•Physical
•Role
•Emotional
•Social
•Cognitive
Symptoms
•Pain
•Fatigue
•Shortness of breath
•Anorexia
•Lower limb weakness
•Palpitations
•Night sweats
Ideally, QoL scores and symptoms should distinguish tumour type
and correlate with “burden of disease”, i.e. severity and stage

6. Chronic Myeloproliferative Neoplasms:
Fatigue and Symptoms
Mesa, et al. Cancer ,2007
Essential Thrombocytemia (N = 304)
Fatigue Itching Night
swears
Bone
pain
Fever Weight loss

7. Chronic Myeloproliferative Neoplasms: Fatigue
and Symptoms

8. AML in elderly patients: prevalent issues
AML - median age of incidence >65 years
• Dismal remission, disease-free survival and overall
survival rates compared with those in younger
patients
• Many elderly AML patients are unfit for intensive
chemotherapy - generally managed with palliative
approaches (Burnett AK et al, 2007).

9. AML in elderly patients:
QoL at diagnosis - a prognostic factor for survival
Oliva E, et al, 2011
Daily clinical practice:
Evaluation of QoL at baseline
as a potential variable that
may be integrated in the
process of decision-making
for treatment allocation

10. Lymphomas: issues
• Hodgkin’s Lymphoma (HL)
> 90% of patients with early stage HL are typically cured
most of the patients in advanced stage HL a chance of cure
treatment is accompanied by acute and long-term complications
modifications of treatment schedules have resulted in better survival and
reduced toxicity.
• Non Hodgkin’s Lymphoma (NHL)
Heterogeneous
In indolent NHL (“incurable”), PROs invaluable, especially in the absence of
clear survival differences among the various treatment strategies.
In aggressive NHL, PROs as endpoints in clinical trials to provide further
insights into the important tradeoffs of alternative regimens.

11. Multiple myeloma (MM): prevalent issues
Cure (permanent eradication of the myeloma clone), is rarely achieved.
• Treatments, such as thalidomide, lenalidomide, and bortezomib, have
increased the average survival from 2-3 years to 5-7 years (Morgan GP,
et al, 2006; Blade J, Rosinol L, 2009).
• Long-term follow-up: a pattern of ongoing relapse, even from long-
standing complete response or partial complete response.
• MM is characterized by a considerable worsening of QoL
reduced physical and role functioning, fatigue, and pain, as the
major problems (Wisloff F, 1996a; Wisloff F, 1996b; Gulbrandsen N,
et al, 2001).
• Treatment of MM is toxic in itself and has a negative impact on patient
QoL. It may be accompanied by multiple side effects
• Durable remission and QoL are considered as primary goals of MM
treatment (Durie BG, 2005).

12. Results of the Myeloma Euronet International Survey in 2009
“Myeloma Treatment Side Effects and Unmet Patient Needs”
• HCP: neuropathy has the most negative impact on a myeloma patient’s overall
well-being
• Patients and patient relatives/caregivers: fatigue, malaise, weakness, dizziness,
somnolence, sedation, and insomnia were the treatment side effects with the
most negative impact on a patient’s overall well-being.
• Patients and HCP: “not too satisfied” or “not satisfied at all” with the psycho-social
support offered.

13. Chronic myeloid leukemia (CML) vs General Population
Efficace F. Blood, 2011
448 CML patients, SF-36
• Most important results:
Younger patients (age 18 -39 years) had marked
impairments in role limitations because of physical and
emotional problems, respectively: -22.6 (P < .001), -22.3 (P
< .001).
Older patients (≥60 years) had a HRQOL profile very similar to
that reported by the general population.
Fatigue was the most frequently reported symptom.
Daily clinical practice:
special attention for PROs in younger patients

14. Chronic myeloid leukemia (CML): prevalent issues
Efficace F., Annal Hematol, 2012
236 patients on imatinib therapy vs health-care professionals
(HCP)
• Most important issues:
PROs: Fatigue, muscle cramps, swelling, worries, and
uncertainty about future health condition
Patients valued some issues related to symptoms much
higher
Importance of social support in coping with the disease.
Daily clinical practice:
Better symptom assessment and management could be the
crucial aspects to improve HRQOL of CML patients.

15. Myelodysplastic syndromes (MDS): Prevalent issues
Primarily elderly patients. Cure is rarely achieved.
• Heterogeneous; variable risk to evolve into AML.
• Cytopenias; 90% of patients experience anaemia, which adversely
affects the quality of life (QoL) and clinical outcomes
• Comorbidities are a major determinant of QoL in MDS (Oliva, Am J
Blood Res, 2012).
• Treatment and PROs:
supportive care, mainly transfusions, remains the main treatment
option and has a negative impact on QoL (Oliva, 2002 and 2012).
Erythroid responses to treatments (ESAs, lenalidomide,
azacytidine, decitibine) associated with improvements in survival
and HRQoL

16. Themes from Focus Group Discussions in patients
with myelodysplastic syndromes (MDS)?
Thomas M, J of Supp Oncol, 2012

17. The Effects of Neutropenia
Problem Domain Patients' Own Words
Physical Complaints
Tired, fatigued, exhausted, weak, feeling
"drained" If I walk from one room to the next, I'm worn out.
Reduced sexual activity
It has definitely slowed down. I don't have a great deal of
interest.
Daily Routine Disruptions
Loss of daily routine I have stopped going to church and taking my son to school.
Difficulties with household activities
I have stopped most everything. I am not doing my
housework.
Negative Thought and Self Evaluation
Worrying about paying for extra care needed If I don't work, I don't get paid. It's getting very scary.
Feeling useless/helpless, letting people down
I feel guilty when I see other people doing work I should be
doing.
Negative Emotions
Feeling down I feel like giving up. I just wish it would all end.
Feeling anxious
I am scared. I hope I don't have to go through this
(neutropenia) the next three times I come here.
Social Relationships
Decreased social contacts and activity I can't spend time with other people because I am sick.
Avoiding crowds
I don't go out because someone might hug me or sneeze
near me. Fortner et al. BMC Nursing 2005

18. Contents
Treatment and Adherence
Quality of life issues important to patients with
hematological malignancies
EHA SWG Project
Burden of Hematological Malignancy
Conclusions

19. Transfusion-dependence and QoL
 Dependence on hospital and staff
 Inability to travel
 Anxiety to receive transfusion
 Adverse events
 Fluctuations in Hb
 Symptoms (dyspnea, difficulty in climbing stairs)

20. 0
20
40
60
80
100
p=0.006
Physical
p=0.06
Functional
p=0.08
Social Fatigue
p=0.15 p=0.0008
MDS-specific
QOL-Escores(median)
Non transfused
Transfused
Low-intermediate IPSS risk MDS patients stratified by RBC-transfusion-
dependence, N= 147
QoL was assessed using the MDS-specific instrument, QOL-E
QoL at diagnosis in myelodysplastic syndromes (MDS)
is influenced by transfusion-dependence
Oliva EN, et al. Am J Blood Res, 2012
IPSS = International Prognostic Scoring System
RBC = Red blood cell

21. Session topic: Quality of life and health economics Caocci et al. Abstract: S147 oral presentation, EHA 2015
Patient-physician relationship in MDS
LOW-RISK MDS

22. Changes in quality of life in anemic MDS patients
with del5q treated with lenalidomide
QOL-EscoresQOL-Escores
Fatigue QoL MDS QoL TOI QoL
0 12 24 52 wks
20
40
60
80
0
±9
±14
±18
±17
P=0.03
P for trend=0.059
0 12 24 52 wks 0 12 24 52 wks
±15
±34
±35 ±39
P for trend=0.17
±14
±25
±15 ±8
P for trend=0.039
Physical QoL Functional QoL Social QoL
0 12 24 52 wks
20
40
60
80
0
±17
±26
±22 ±16
P for trend=0.01
0 12 24 52 wks 0 12 24 52 wks
±7
±34
±35
±39
P for trend=0.02
±19
±35
±22
±31
P for trend=0.01
±8
±24
±29
Oliva EN, et al. Leuk Lymph 2013

23. Effects of first-line treatment and progression
on QoL in multiple myeloma
Delforge, et al. Jun 13, 2014; 53809 E poster, EHA 2015

24. Hélène Gilet (Jun 14, 2014; abstract 54294) , E poster EHA 2015
MULTIPLE MYELOMA
Patient-physician relationship in multiple
myeloma

25. Oliva et al. ASH 2015 poster presentation
Changes in QoL in elderly AML patients undergoing
intensive chemotherapy

26. Main Reasons for Non Adherence
– AARP 2004
USA , AGE ≥ 50 years
 Cost of the drug 40%
 Side effects of drug 11%
 Thought drug wouldn’t help much 11%
 Didn’t think I needed it 8%
 Drug did not help 6%
 Don’t like taking prescription drugs 5%
 Condition improved 4%
 Already taking too many prescriptions 3%

27. Contents
Treatment and Adherence
Quality of life issues important to patients with
hematological malignancies
EHA SWG project
Burden of Hematological Malignancy
Conclusions

28. Project to Develop a Patient-Reported Outcome Measure
in Haematological Malignancies for Use in Clinical
Practice

29. Aims and Objectives
Aims
 Investigate the impact of a wide range of haematological malignancies and their
treatment on patients’ QoL and symptoms.
 Develop and validate an instrument designed to measure the impact of
haematological disease and treatment on individual patients QoL and
symptoms in daily clinical practice
 Compare and contrast the impact of disease and treatment on patients’ QoL
and symptoms across different haemotological conditions.

Primary endpoints:
 1. The generation of items to construct a PRO instrument for patients with
haematological malignancies for use in routine clinical practice.
 2. Psychometric evaluation of the instrument including validity, reliability
and sensitivity in patients with haematological malignancies in clinical practice
setting.

30. Conclusions
Treatment and progression are associated with significant QoL changes,
with variability according to baseline QoL status
Quality of life issues important to patients with
hematological malignancies
A “daily practice calculator” of PROs may be useful to evaluate disease
status and impact of treatment
Hematological malignancies vary in their impact on QoL and symptoms