Transcript Issues in Haematological Malignancy 2010 Prof. A H

Issues in Haematological Malignancy
2010
Prof. A H Goldstone CBE
AML
• ALL
• CML
• CLL
• Myeloma
• Lymphoma
•
There is more that can be achieved
almost everywhere and the PCTs
and Insurance Companies
are running scared
The patient over 70 years starts
to get proper treatment!
AML – Acute Myeloid Leukaemia
•
The elderly still do badly
•
Targeted therapy
anti CD33 (Mylotarg)
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RIC transplant for the older patient - (50-65)
ALL – Acute Lymphoblastic Leukaemia
•
Adults still do badly
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•
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Antibody treatment arrives
•
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Kids 90% survival
Adults 35% survival
Rituximab may also be useful in ALL
More transplant!•
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Unrelated donors transplant increasing
RIC (reduced intensity conditioning)
CML – Chronic Myeloid Leukaemia
•
Arrival of tyrosine kinase inhibitors (TKIs)
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Imatinib (Glivec) “wonder drug” now produces 90%
10 year survival
•
Probably needs to be continued indefinitely £25K/yr
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Very few patients now need transplanting
CLL – Chronic Lymphocyte Leukaemia
Strategy moves from “suppression” to induction
of remission
• FCR (Fludarabine, Cyclophosphamide,
Rituximab)
• More complex treatment, more
immunosuppression, more commitment of
patient
• Younger patients should be considered for
transplant – this disease is sometime CURABLE!
•
Myeloma
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Drugs begin to be effective
Thalidomide
Bortezomib (Velcade)
Lenalidomide (Revlimid)
Side effects are considerable and need close
monitoring
Outlook now increased from 2-3 yrs to 6-8 yrs
Every patient of whatever age worthy of
consideration of first line therapy
So you thought Lymphoma
was a rare disease –
not any more
Lymphoma is:•
The most common blood cancer, more
common than leukaemia and myeloma
•
Most common cause of blood cancer death
•
5th leading cause of cancer death in men, 4th
in women
•
Causes 11% of childhood cancers
•
Increasing 4%/year
Non-Hodgkin’s Lymphoma
Incidence and Mortality Rates
Age-specific incidence rate (case numbers per
100,000 per year) for cases of NHL collected
from geographically defined areas of the UK
1984-1993
Lymphoma – A growing problem
Increasing incidence of NHL
Non-Hodgkin's
Lymphoma
Hodgkin's
Lymphoma
Australian Institute
of Health and
Welfare 2000
The following table gives the estimated numbers
of new cases and deaths for each
common cancer type:
Cancer Type
Estimated New Cases
Estimated Deaths
Bladder
68,810
14,100
Breast (Female-Male)
182,460-1,990
40,480-450
Colon and Rectal
(Combined)
148,810
49,960
Endometrial
40,100
7,470
Kidney (Renal Cell) Cancer
46,232
11,059
Leukaemia (ALL)
44,270
21,710
Lung (Including Bronchus)
215,020
161,840
Melanoma
62,480
8,420
Non-Hodgkin’s
Lymphoma
66,120
19,160
Pancreatic
37,680
34,290
Prostate
186,320
28,660
Skin (Nonmelanoma)
>1,000,000
<1,000
Thyroid
37,340
1,590
•
Approximately 1.5 million people
worldwide are living with non-Hodgkin’s
lymphoma (NHL)
•
It is estimated that 300,000 people die
each year from the disease
Facts and Figures
1 new case of lymphoma is diagnosed every 9
minutes*
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1 in 50 people will develop lymphoma*
81% increase in incidence of NHL between 19731990
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Overall survival at 5 years is 50%-60% for all nonHodgkin’s lymphomas
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*US statistics
Ries LAG, et al. SEER Cancer Statistics Review, 1975-2000, National Cancer Institute. Bethesda, MD
Cancer Facts & Figures 2004, www.cancer.org
Lymphoma: Current Challenges
•
Continued increase in incidence 3-4% increase in
annual incidence of NHL over last 2-3 decades
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Diverse disease made up of numerous subtypes.
Careful patient selection necessary to maximize
treatment benefit
•
Despite improvements in outcomes over the past
decade, some subgroups of NHL, in particular,
remain difficult to treat
•
Development of newer treatment strategies critical
to improving outcomes
Müller A et al. Ann Hematol. 2005;84:1-12; Hagemeister FB.
New agents in the treatment of lymphomas: which ones will succeed. Available at:
www.cmeinteractive.cancerconsultants.com/ShowArticle.aspx?ArticleID=2.
Non-Hodgkin Lymphoma: Incidence
Other subtypes with a frequency ≤ 2% (9%)
Peripheral T-cell (6%)
Follicular lymphoma (22%)
Mantle cell (6%)
Composite
lymphomas
(13%)
Small lymphocytic
lymphoma (6%)
Marginal zone B-cell
lymphoma MALT type
(5%)
Marginal zone B-cell
lymphoma nodal type (1%)
Diffuse B-cell lymphoma
(31%)
Lymphoplasmacytic
lymphoma (1%)
Armitage et al. J Clin Oncol. 1998;16:2780-2795.
Low Public Awareness of Lymphoma
According to a study of lymphoma patients carried out
in 2003:
•
Prior to diagnosis almost all respondents (97.5%) had been
unaware of non-Hodgkin’s lymphoma
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Many patients with non-Hodgkin’s lymphoma do not have an
accurate understanding of the disease
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Up to 35% of respondents were vague about the body parts
affected by non-Hodgkin’s lymphoma
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Half of respondents were unaware of their specific diagnosis
Cause-specific Survival of NHL Study
Patients
(1974–1995)
Cumulative survival (%)
100
80
60
Aggressive NHL
40
Indolent NHL
20
0
0
5
10
15
Time (years)
20
25
30
Other reasons for incidence of
NHL
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Many are age-related
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Auto-immune disease
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Environmental chemicals
Lymphomas associated with host
susceptibility factors
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Enteropathy – associated T-cell Lymphoma
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Extranodal and systemic EBV + T/Non-Hodgkin’s
Lymphoma
- Genetics
- Gliadin allergy
- Genetics
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Hepatosplenic T-cell Lymphoma
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Burkitt
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Post transplant Lymphoma
- Immunosuppression + chronic autogenic
stimulation
- Malaria + HIV
- Iatrogenic immunosuppression
HIV – associated Lymphomas
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DLBC
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Primary CNS Lymphoma
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Burkitt
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Primary Effusion Lymphoma
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600 fold increase for immunoblastic Lymphoma
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14 fold xs for low grade Non-Hodgkin’s Lymphoma
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Hodgkin’s Lymphoma
Lymphoma associated with
Infectious Agents
• Nasal, cutaneous NK/T
EBV
• Adult T-cell leukaemia Lymphoma
HTLV1
• Marginal zone
H.pylori, campylobacter, Hepatitis C
• Primary effusion Lymphoma
HHV-8/KSHV
A Cancer in Disguise
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Symptoms are commonly seen in other, less
serious illnesses, such as influenza or other viral
infections and are often overlooked
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Symptoms can appear anywhere in the body
Diagnosis of NHL
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Physical examination
Chest X-ray
Ultrasound
CT scan & PET Scan
Bone marrow biopsy
Blood test, incl. cell surface marker phenotype
Sometimes:
• Cytogenetics
• Gene rearrangement
• Liver biopsy
• MRI
The greatest increase is in skin
Lymphoma
NHL and occupation
CAUTION
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Is the rise apparent and not real?
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Are we just better at finding and
diagnosing?
New diagnostic and therapeutic
areas in Lymphoma
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PET scanning
- diagnosis
- activity
- prognosis
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Immunohistochemistry
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Targeted therapies
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Stem cell transplantation
- eg Rituximab
The Rationale for Transplant in
Lymphoma
Auto
• Dose
Conventional Allo
• DOSE
• ALLO EFFECT
Mini-Allo
• DOSE
• ALLO EFFECT
PET+ve after 2# ABVD predictive of
treatment failure in HL

PET-2-ve: 2yr FFS 96%
(n=161)
PET-2+ve: 2yr FFS 14%
(n=41)
Gallamini et al, ASH 2006 (n=202)
Hodgkin Lymphoma
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Normally 5 x less frequent than NHL
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More frequent also in HIV patients
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Now 2 subtypes
- Classical
- NLPH (nodular lymphocytic predominant)
Radiotherapy in Hodgkin’s
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Much less frequently used today
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Major problem with Breast Cancer after “Mantle”
field
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Chemo more toxic short term but less toxic long
term
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Fertility issues with new escalated chemo
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Issues of “Survivorship”
Why Targeted Therapies?
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Need to improve outcomes for all types of lymphoma
-Improve cure rate for aggressive lymphomas
-Maintain remission for indolent disease
-Eradicate minimal residual disease
-Decrease relapse rate for all lymphoma
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Lymphoma frequently associated with deregulated cellular
pathways of differentiation, proliferation or survival
-Molecules involved in these aberrations provide rational
targets for selective therapies
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Agents generally well tolerated and easily combined with
other therapies (eg, chemotherapy, radiotherapy)
Coiffier B. Semin Oncol. 2004;31(1 suppl 2):7-11.
Targeting the Cell Surface
slg
CD19
CD20
CD22
DR
B Lymphocyte
Major Themes
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Effectiveness without toxicity.
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Dose escalation
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Exploitation of passive & active
immunotherapy
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The ongoing management of the
patient with active disease is vital
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Lymphoma, Myeloma + CLL are of
major importance in this regard
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“Living with Cancer” has truly arrived
in many haematological malignancies