Transcript Document

Accessing Care for Myeloma and
Outcomes in British Columbia
Vancouver October 2010
Kevin Song MD FRCPC
Leukemia/BMT Program of B.C.
Clinical Case
•
•
•
•
•
60 y.o. previously healthy male.
Progressive back pain over 2 months
Repeated urinary tract infections.
Blood work revealed anemia
Other blood test:
– mild kidney function changes
– increased proteins
– IgG monoclonal gammopathy
Clinical Case
• Bone Marrow Biopsy: 50% plasma cells
• Skeletal survey: diffuse lytic lesions
• November 1999: Myeloma diagnosed
Questions running through one’s
mind
•
•
•
•
•
•
•
•
What is myeloma?
How long do I have to live?
What will my quality of life be?
Am I getting the right treatment?
Do I have the right Doctor?
Am I in the right country/province?
What can I do to improve my chances?
Why can’t I get these drugs/treatments?
Outline of Talk
1. Increasing options and improving
outcomes
2. Basics of Clinical trials
3. Getting Drugs funded by government
4. Status of medications in BC
5. Improving access to drugs for all
patient
6. Local outcomes
Natural history of MM
Asymptomatic
Symptomatic
M Protein (g/L)
100
ACTIVE
MYELOMA
RELAPSE
50
20
REFRACTORY
RELAPSE
RELAPSE
MGUS* or
smoldering
myeloma
Plateau
remission
Transplant
Therapy
Therapy
Historical Perspective of
Multiple Myeloma
High-dose therapy
with autologous
stem cell support
HDAC inhibitors, HSP
inhibitors, +++
bortezomib
Bisphosphonates
lenalidomide
Thalidomide
Oral melphalan
and prednisone
1962
1996
1999
2004
2006
2008+
Impact of Novel Agents on the Outcome in Post
ASCT Relapsed/refractory Disease (n=387)
1.0
Relapsed before 1998
Relapsed 1998–1999
Relapsed 2000–2001
Relapsed 2002–2003
Relapsed 2004–2005
Survival
0.8
0.6
0.4
P<0.001
0.2
0.0
0
20
40
60
Time (months)
80
100
Kumar et al Blood 2008
Investigational Agents in MM
New Drug Development
Phase I
Phase II
Phase III
In Use
How are Subjects Protected
during a Clinical Trial?
• Ethics Board approves the research
protocol
• Health Canada: GCP guidelines
• Your Study Team: Doctors, Nurses,
Pharmacists
• Confidentiality
Phase I
• Small trials: 15- 50 subjects
• find optimal dose
– safe dose range
– side effects
– pharmocologic behaviour (and how the
body copes with the drug)
– To determine how well the drug works
Phase II
• To evaluate the effectiveness in a larger
population
• Focus is often for which no effective
treatment exists
• All subjects receive the same dose
• To assess effectiveness of drug or therapy
– To assess for additional safety information
Phase III
• Large multi-centre trials with 100+ subjects
• Survival time and quality of life measured
• Subjects are randomized to a:
– Study Group (receiving study drug) or
– Control Group (receiving standard of care)
• To determine whether a new therapy or
drug is more effective or has fewer side
effects than the standard of care
From Trials to General Use
1. Health Canada Reviews data and gives
approval for use
2. The Provincial agencies examines the
ability to fund the drugs
•
•
Review by “experts” national and local
In BC, the Priorities and Evaluations Committee
3. Drug is approved for funding or rejected
•
•
Costs
Efficacy
Provincial Oncology Drug Budget
(in million Cdn $ with annual growth)
160
15%
140
14%
14%
120
10%
100
22%
20%
80
60
48%
16%
8%
44%
40
25%
13%
20
0
98/99 99/00 00/01 01/02 02/03 03/04 04/05 05/06 06/07 07/08 08/09 09/10
Monthly and Median Costs of Cancer
Drugs at the Time of Approval by the
FDA from 1965 through 2008
Bach NEJM 2009; 360:626-633
Funding for New Treatments
● Provincial Oncology Drug Budget
~ $150 million for 2009/10
● Challenge: new drugs
~ $50,000 per patient per year
● BCCA Priorities & Evaluation Committee (PEC)
est. 1997
● BCCA Compassionate Access Program (CAP)
est. 2006
Myeloma Drugs
Drug
Melphalan
Year of
Approval
(USA)
1992
Monthly Medicare
Price at time of
Approval
$35
Bortezomib
2003
$3,392
Lenalidomide
2005
$8,535
Thalidomide
2006
$5,998
Bach NEJM 2009; 360:626-633
Increasing number of referrals
and transplants at the VGH
Myeloma Referrals and Transplants
Year
Referrals
Transplants
140
2001
71
44
120
2002
55
45
2003
43
32
2004
84
55
2005
80
52
2006
97
62
2007
107
81
2008
117
83
number
100
80
Series1
Series2
60
40
20
0
1
2
3
4
5
Year 200x
6
7
8
Hematology Research & Clinical
Trials Unit (HRCTU) est. 2005
 Produce and evaluate new treatments for
blood diseases
 more effective
 less toxic
 Provide BC residents with access to new
treatments earlier than otherwise possible
 Improve quality of life for patients with blood
diseases
 Minimal support by government
Status of Lenalidomide
(Revlimid®) in BC
• Initially available for myeloma through
expanded access protocol at the VGH
2005
• Approved by Health Canada in Autumn
2008
• BC Cancer Agency funds lenalidomide
as of 2009
ec
Ja 05
n
Fe -06
b
M -06
ar
A p 06
r-0
M 6
ay
Ju 06
n0
Ju 6
l
A u - 06
g
S e - 06
pO 06
ct
N -06
ov
D - 06
ec
Ja 06
n
Fe -07
b
M -07
ar
A p 07
r
M -07
ay
Ju 07
n0
Ju 7
l-0
Au 7
g
S e - 07
pO 07
ct
N -07
ov
D - 07
ec
Ja 07
nF e 08
b
M -08
ar
A p 08
r
M -08
ay
-0
8
D
# of Patients
Patients on Revlimid
150
145
140
135
130
125
120
115
110
105
100
95
90
85
80
75
70
65
60
55
50
45
40
35
30
25
20
15
10
5
0
Month
Patients off Study
Patients on Study
Status of Bortezomib (Velcade®)
in BC
• Initially available for myeloma through
expanded access protocol at the VGH
2004
• BC Cancer Agency funds for relapsed
myeloma in 2005
• BC Cancer Agency funds for newly
diagnosed transplant ineligible myeloma
in 2010
HRCTU – Examples of Impact
■ Multiple myeloma
● Lenalidomide and Bortezomib
● 169 patients treated
● $5.0 million drug savings
● Patients got drug early
Vancouver: OS from time of Dx
Similar Results as Other Centers
Median not yet reached
P = 0.001
73.9 mo
Venner et al. ASH 2009 (abstract 2872)
EFS post transplant:
Improved survival benefit is not from improved
Transplants
P = 0.051
15mo
20mo
Venner et al. ASH 2009 (abstract 2872)
Post-Relapse Survival
Pre and post 2004:
Survival benefit is from post-relapse treatment
P < 0.001
43mo
16mo
Venner et al. ASH 2009 (abstract 2872)
Impact of New Drugs on
Survival in BC
Date of Diagnosis
% alive at 5 years
Before 2003
50%
2003 and beyond
70%
Why do Studies?
• Treatment of Myeloma is rapidly changing
– Novel therapies are being developed
• New drugs may be approved in BC/Canada
later than other parts of the world
– Novel therapies are expensive
– Improve the ability of getting drug to the
population of BC
• Attract more trials
Experimental Drugs tested or
being tested in Vancouver
1.
2.
3.
4.
5.
6.
7.
Bortezomib
Lenalidomide
Liposomal doxorubicin
CNTO 328
Carfilzomib
Pomalidomide
LBH (HDAC inhibitor)
Guiding Principles
Research
Drug Access
Patients
Quality of Life
Which Trials To Do?
• Sponsors offer trials based upon:
– Size of center and possible number of participant
– Prior experience with the center
• We approach sponsors
• Most promising drugs trials selected
– Most likely of benefit
– Convenience ( so people far away may be able to participate)
• Avoid competing trials
– Need to enroll an appropriate number of patients to make it
worthwhile for the sponsor and trials unit
• Ability to sustain the trials unit
– If the unit becomes bankrupt we cannot do any trials
Are Trials done outside of the
Vancouver General Hospital in BC?
• Smaller hospitals do not have as strong
an infrastructure or referral base
– Trials are center specific
– Ethics Boards are center specific
– Infrastructure
• Attempts to have trials at other BCCA
sites
What about trials being done
outside of BC ?
• Other Referral Centers do similar and
different trials. May sites will give
information regarding this.
• Cost to subject (patient) can be higher
• Travel
• Not considered standard treatment
Case Continued
• February 2000: Successful transplant but Minimal
Response
• July 2001: Melphalan and prednisone – MR
• January 2002: Thalidomide dexamethasone –
some response but problems with blood clot and
nerve damage
• December 2002: Cyclophosphamide and
prednisone – MR
• September 2004:Bortezomib (Velcade) on trial –
best response lasting 2 year
Case Continued
• December 2006: Lenalidomide (Revlimid)
on trial – response for 1 year
• September 2007: Bortezomib
• Spring 2008: Bortezomib
• Fall 2008: Lenalidomide
• Spring 2009: Carfilzomib
• Summer 2009: Death from myeloma
Conclusions
•
•
•
•
Improved Survival with newer agents
Even newer agents are being investigated
Cost of drugs remain a concern (access?)
Clinical trials help improve access
– Earlier availability of drugs
– Experience of physicians and nurse with new drugs
– Local experience strengthen applications for drug funding
• Myeloma still remains incurable and patients require
a lot of care.
We Don’t Want to be Left Behind