NATIONAL INSTITUTE FOR HEALTH AND CARE EXCELLENCE
Proposed Health Technology Appraisal
ATIR101 with haematopoietic stem cell transplantation for
haematological cancers
Draft scope (pre-referral)
Draft remit/appraisal objective
To appraise the clinical and cost effectiveness of ATIR101 as an adjunct to
haematopoietic stem cell transplantation within its marketing authorisation for
haematological cancers.
Background
Haematological cancers are a diverse group of cancers that affect the blood,
bone marrow, and lymphatic systems. Among the categories of
haematological cancer, there are acute lymphoblastic leukaemia (ALL), acute
myeloid leukaemia (AML) or myelodysplastic syndrome (MDS). Treatment for
haematological cancers may involve a combination of chemotherapy and
radiotherapy. Between 10-40% of people with acute leukaemia do not achieve
complete remission despite 1 or 2 cycles of intensive combination induction
chemotherapy. Haematopoietic stem cell transplant (HSCT) may be an option
at this stage if the person is suitable and a donor is available.
Allogeneic haematopoietic stem cell transplantation offers the best chance for
a cure for acute leukaemia. Allogeneic transplants (from someone else’s cells)
come from a matched sibling or unrelated donor who has all 6 human
leukocyte antigens (HLA) at the HLA-A, B, and DR loci matching the recipient.
Approximately 70% of people needing HSCT do not have a matched sibling
donor. Donor registries can provide a source for HLA-matched unrelated
donors, but haematological cancers can advance rapidly which can limit the
time available for finding unrelated donors. Additionally, HLA-matched
unrelated donors are rarely found across ethnic groups and can therefore limit
the number of possible donors for people from minority ethnic groups.
Another type of donor is a haploidentical related donor, or a donor whose HLA
loci are a 50% match to the recipient. By definition, the parent of a child will
always be a haploidentical donor since half of the recipient’s genetic material
comes from each parent. There is a 50% chance that a sibling will be a
haploidentical donor. More than 90% of people needing a haematopoietic
stem cell transplant have a haploidentical family member. Other advantages
of haploidentical haematopoietic stem cell transplant include: immediate
donor availability; access for all regardless of ethnicity; the ability to select the
best donor on the basis of age, sex, and infectious disease status; and access
to repeated donation in case of transplant failure.
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of ATIR101 with haematopoietic stem cell
transplantation for haematological cancers
Issue Date: January 2017
Page 1 of 6
After HSCT treatment it can take six to twelve months blood cell levels and
immune cell functions to become near-normal. During this time there is a high
rate of transplant rejection, graft versus host disease (GVHD) (when donated
white T-cells attack the body’s own cells), and also to disease relapse and
transplant-related mortality.
It is estimated that there are around 900 stem cell transplants using unrelated
donor stem cells in England each year. Of these, around 800 are estimated to
be for haematological malignancy (90%). Of these around 280 people will
need an urgent stem cell transplant but not be able to find a matched donor in
time (35%). Of these people around 265 people will have a partially matched
family donor available (95%). It is estimated that between 20% and 80% of
patients undergoing an allogeneic HSCT will develop some form of GvHD.
The development of acute GvHD is directly related to the level of HLA
mismatch and varies between 10-80% depending on risk factors such as
mismatched donors and older age. Approximately 30-70% of allogeneic
HSCT recipients surviving longer than 100 days post-transplant will develop
chronic GvHD within 4-6 months post HSCT4.
The current UK approach to approach to haploidentical HSCT, is to provide
patients with a T-lymphocyte replete transplant, followed by treatment with
prophylactic cyclophosphamide to destroy any activated T-lymphocytes that
may cause GvHD. Standard treatment of GVHD is with ciclosporin,
methotrexate and corticosteroids.
The technology
ATIR101 (Brand name unknown, Kiadis Pharma) is a T-lymphocyte enriched
leukocyte preparation depleted of host alloreactive T cells ex vivo from
hapoidentical donor samples using light exposure technology. It is
administered to patients who have received a haploidentical HSCT from the
same donor as the donor of the cells in ATIR101. It is administered by
intravenous infusion.
ATIR101 does not currently have a marketing authorisation in the UK for
haematological cancers. It has been studied in non-randomised, uncontrolled
phase II clinical trials in adults with a hematologic malignancy including ALL or
AML (in first remission with high-risk features or in second or higher
remission) or MDS (transfusion-dependent, or intermediate or higher IPSS-R
risk group), who received a CD34-selected HSCT from a haploidentical donor.
Intervention(s)
ATIR101 as an adjunct to haematopoietic stem cell
transplantation
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of ATIR101 with haematopoietic stem cell
transplantation for haematological cancers
Issue Date: January 2017
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Population(s)
Adults with a haematological malignancy (acute
lymphoblastic leukaemia, acute myeloid leukaemia or
myelodysplastic syndrome) who are suitable for a
hematopoietic stem cell transplant from a haploidentical
donor
Comparators
Established clinical management without ATIR101
Outcomes
The outcome measures to be considered include:
Economic
analysis

incidence and severity of graft versus host
disease

mortality

overall survival

progression free survival

GvHD-free, relapse-free survival

adverse effects of treatment

health-related quality of life.
The reference case stipulates that the cost effectiveness
of treatments should be expressed in terms of
incremental cost per quality-adjusted life year.
The reference case stipulates that the time horizon for
estimating clinical and cost effectiveness should be
sufficiently long to reflect any differences in costs or
outcomes between the technologies being compared.
Costs will be considered from an NHS and Personal
Social Services perspective.
Other
considerations
If the evidence allows the following subgroups will be
considered. These include:

patients with acute myeloid leukemia

patients with acute lymphoblastic leukemia

patients with myelodysplasic syndrome
Guidance will only be issued in accordance with the
marketing authorisation. Where the wording of the
therapeutic indication does not include specific
treatment combinations, guidance will be issued only in
the context of the evidence that has underpinned the
marketing authorisation granted by the regulator.
Related NICE
recommendations
Related Guidelines:
‘Haematological cancers: improving outcomes’ (2016),
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of ATIR101 with haematopoietic stem cell
transplantation for haematological cancers
Issue Date: January 2017
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and NICE
Pathways
NICE guideline 47
Related Quality Standards in development:
‘Haematological cancers’. NICE quality standard.
Publication expected 2017
Related NICE Pathways:
‘Blood and bone marrow cancers’ (2016) NICE Pathway
‘Blood conditions’ (2016) NICE pathway
Related National
Policy
NHS England Manual for Prescribed Specialised
Services (Chapter 29: Blood and marrow transplantation
services, adults and children):
NHS England (2013) NHS Standard Contract for
haematopoietic stem cell transplantation (adult) Ref:
NHS England: B04/S/a
NHS England (2013) Clinical Commissioning Policy:
Haematopoietic Stem Cell Transplantation Ref: NHS
England: B04/P/a
Department of Health, NHS Outcomes Framework
2016-2017 (published 2016):
https://www.gov.uk/government/publications/nhsoutcomes-framework-2016-to-2017
Questions for consultation
How many patients are likely to be eligible for ATIR101 as an adjunct to
HSCT in England?
How is a ‘partial match’ defined in clinical practice in England?
What is the current protocol for haploidentical haematopoietic stem cell
transplantation in the NHS? For example, does it involve providing a Tlymphocyte replete transplant, followed by treatment with prophylactic
cyclophosphamide? What treatments are considered established clinical
practice in the NHS for prevention or treatment of graft versus host disease?
Have all relevant comparators for ATIR101 been included in the scope?
Are the outcomes listed appropriate? Have the outcomes of most relevance to
patients been included?
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of ATIR101 with haematopoietic stem cell
transplantation for haematological cancers
Issue Date: January 2017
Page 4 of 6
Are the subgroups suggested in ‘other considerations appropriate? Are there
any other subgroups of people in whom ATIR101 is expected to be more
clinically effective and cost effective or other groups that should be examined
separately?
Where do you consider ATIR101 will fit into the existing ‘Blood and bone
marrow cancers’ NICE pathway?
NICE is committed to promoting equality of opportunity, eliminating unlawful
discrimination and fostering good relations between people with particular
protected characteristics and others. Please let us know if you think that the
proposed remit and scope may need changing in order to meet these aims.
In particular, please tell us if the proposed remit and scope:

could exclude from full consideration any people protected by the equality
legislation who fall within the patient population for which ATIR101 is
licensed;

could lead to recommendations that have a different impact on people
protected by the equality legislation than on the wider population, e.g. by
making it more difficult in practice for a specific group to access the
technology;

could have any adverse impact on people with a particular disability or
disabilities.
Please tell us what evidence should be obtained to enable the Committee to
identify and consider such impacts.
Do you consider ATIR101 to be innovative in its potential to make a significant
and substantial impact on health-related benefits and how it might improve the
way that current need is met (is this a ‘step-change’ in the management of the
condition)?
Do you consider that the use of ATIR101 can result in any potential significant
and substantial health-related benefits that are unlikely to be included in the
QALY calculation?
Please identify the nature of the data which you understand to be available to
enable the Appraisal Committee to take account of these benefits.
NICE intends to appraise this technology through its Single Technology
Appraisal (STA) Process. We welcome comments on the appropriateness of
appraising this topic through this process. (Information on the Institute’s
Technology Appraisal processes is available at
http://www.nice.org.uk/article/pmg19/chapter/1-Introduction)
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of ATIR101 with haematopoietic stem cell
transplantation for haematological cancers
Issue Date: January 2017
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References
1. Cancer Research UK. About graft versus host disease (GVHD). November
2014. http://www.cancerresearchuk.org/about-cancer/coping-withcancer/coping-physically/gvhd/about-graft-versus-host-disease#acute
(accessed November 2016)
2. Health and Social Care Information Centre, Hospital Episode Statistics for
England. Inpatient statistics, 2014-15. www.hscic.gov.uk
3. NHS Blood and Transplant. Unrelated donor stem cell transplantation in the
UK. UK stem cell strategy oversight committee November 2014.
http://www.nhsbt.nhs.uk/ (accessed 13 June 2016)
4. National Institute for Health Research Horizon Scanning Research and
Intelligence Centre briefing ‘ATIR101 for patients with haematological
malignancy who are candidates for haematopoietic stem cell
transplantation – adjunctive therapy’ ID: 4684
National Institute for Health and Care Excellence
Draft scope for the proposed appraisal of ATIR101 with haematopoietic stem cell
transplantation for haematological cancers
Issue Date: January 2017
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