Chimeric antigen receptor T-cells in New Zealand: challenges and opportunities
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Chimeric antigen
receptor T-cells in
New Zealand: challenges
and opportunities
Robert Weinkove, Philip George, Myra Ruka, Tia Huia Haira, Giulia Giunti
ABSTRACT
Chimeric antigen receptor (CAR) T-cells are a personalised cell and gene therapy for cancer that are becoming
an international standard of care for some refractory B-cell leukaemias, non-Hodgkin lymphomas and
myeloma. A single CAR T-cell administration can result in durable complete response for some recipients.
Domestic CAR T-cell manufacturing capability was established for Aotearoa New Zealand’s first CAR T-cell
trial (ENABLE, ClinicalTrials.gov NCT04049513). This article outlines CAR T-cell manufacturing and logistical
considerations, with a focus on New Zealand’s environment for this personalised cell and gene therapy.
We discuss Māori engagement in CAR T-cell trial and clinical service design, and propose enhancing Māori
guardianship (kaitiakitanga) over cells and genetic material through on-shore manufacture. Strategies
to safely deliver CAR T-cells within New Zealand’s healthcare system are outlined. Finally, we discuss
challenges to, and opportunities for, widening CAR T-cell availability and assuring equity of access. Based on
our experience, we consider Aotearoa New Zealand to be in an excellent position to develop and implement
investigational and commercial CAR T-cell therapies in the future.
C
himeric antigen receptor (CAR) T-cells As a personalised cell and gene therapy,
are an emerging modality of can- CAR T-cells present unique regulatory
cer therapy. CAR T-cells are patient requirements. The logistics of CAR T-cell
lymphocytes that have been engineered to production and delivery, and the potential
express a synthetic receptor, which enables for specific adverse events, demand prepa-
them to target tumour cells.1 Internation- ration by treatment sites. The nature of CAR
ally, CAR T-cell therapies are becoming a T-cell therapies may raise ethical and equity
standard of care. They are a potentially issues that need to be addressed to ensure
curative treatment for certain relapsed equity of access and outcomes.
and refractory (r/r) B-cell malignancies. In We recently established local Good Manu-
adult patients with r/r B-cell lymphomas facturing Practice (GMP) manufacture
and leukaemias, overall response rates of of lentiviral vectors and CAR T-cells and
73–83 % and complete response rates of commenced enrolment to New Zealand’s
51–83 % have been reported following CAR first CAR T-cell trial, ENABLE (Clinical-
T-cell therapy.2–4 These responses can be Trials.gov reference NCT04049513).6 This
durable, with 75% of patients with agres- involved close liaison with regulators and
sive B-cell lymphoma who respond at three stakeholders and multidisciplinary input
months reporting being progression free for safe clinical delivery of CAR T-cell ther-
at 24 months following CAR T-cell therapy.3 apies. Here we build on this experience
Promising results have also been reported by outlining the regulatory landscape
for other malignancies, notably myeloma.5 for CAR T-cell therapies in New Zealand,
CAR T-cell therapies involve a single cell summarising the preparation of sites and
administration, offer curative potential and discussing the opportunities to broaden
can often be delivered in a near-hospital access to this new cancer treatment
outpatient setting. modality in New Zealand.
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CAR T-cell or natural disaster. Māori regard tissue
and genetic material as a taonga (precious
manufacturing item), and international manufacture limits
and logistics opportunities for Māori engagement and
kaitiakitanga (guardianship) over the cells
Leukocyte harvest and and the genetic material they contain11—
leukapheresis the destination(s) and use of the cells must
Figure 1 illustrates a typical CAR T-cell be made clear during consent processes.
manufacturing process. In brief, white In our view, future CAR T-cell manu-
blood cells are collected using an automated facture within Aotearoa, either of locally
apheresis machine or by venesection of developed products or through distributed
whole blood. Following initial processing manufacture of commercial products,12
and purification of T-cells, a new gene (the would improve opportunities for Māori
“transgene”) encoding the CAR is introduced, engagement in the governance of tissue use
typically using a lentiviral or retroviral and disposal.11
vector.7 CAR T-cells are expanded and then Manufacture and release of
either administered fresh or cryopreserved
CAR T-cells
following quality control testing.8
Although not viable except under
Commercially licensed autologous CAR specialised laboratory culture conditions or
T-cell products, such as tisagenlecleucel within the intended recipient (ie, the patient
(tisa-cel) and axicabtagene ciloleucel (axi- who underwent white blood cell collection
cel), require a leukapheresis procedure.7 used for the manufacture of that specific
The New Zealand Blood Service (NZBS) is CAR T-cell product), CAR T-cells are defined
a national service that routinely performs as genetically-modified organisms (GMOs)
leukapheresis for haematopoietic stem cell by New Zealand legislation. Therefore,
harvest across New Zealand. The NZBS is CAR T-cell manufacture is regulated by the
licensed by Medsafe to collect and manu- Environmental Protection Authority (EPA)
facture therapeutic cells by apheresis and under the Hazardous Substances and New
has conducted leukapheresis procedures for Organisms (HSNO) Act 1996 (Table 1).
cellular therapy trials, including our own
Before granting approval to manufacture
ENABLE CAR T-cell trial.9,6,10 Leukapheresis
CAR T-cells for the ENABLE trial, the EPA
product testing for blood-borne viruses is
sought assurance that the cells could not
routinely performed at the Medsafe-licensed
escape into the environment. To meet these
NZBS Donation Accreditation Laboratory.
containment requirements, we modified our
For the ENABLE trial, the leukapheresis
GMP manufacturing facility and its oper-
procedure and leukapheresis product testing
ating procedures. The facility is inspected
is funded from the trial research budget.
and audited by the Ministry for Primary
Manufacturers of commercial and inves-
Industries (MPI) and Medsafe.
tigational CAR T-cell products are likely
to have specific requirements for patient CAR T-cells are manufactured according
identification, infectious agent testing, to validated protocols and must meet
leukapheresis performance and product the requirements of the Pharmaceutical
labelling and shipping—and in our opinion, Inspection Convention/Pharmaceutical
the NZBS network is likely to be well placed Inspection Co-operation Scheme (PICS)
to conduct leukapheresis or venesection Guide to Good Manufacturing Practice
procedures for CAR T-cell manufacture in (Table 1). Once a CAR T-cell product has
New Zealand in the future. been manufactured and met pre-spec-
ified “release criteria,” the CAR T-cells are
Current commercial CAR T-cell therapies
retrieved from storage and prepared for
are manufactured in a limited number of
delivery to the hospital.
centres globally, none of which are in New
Zealand. This offers advantages of scale, Shipping, product traceability,
standardisation and cost, but the need for cell storage and disposal
bidirectional international shipping of cells Release of CAR T-cell products to the
can present a logistical challenge, espe- hospital site for administration to patients
cially if travel is disrupted by pandemic also required EPA approval. Measures to
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Figure 1: Outline of CAR T-cell manufacture. Manufacture of CAR T-cells involves white blood cell harvest, typically by leukapheresis (1), followed by purification of T-cells,
and transduction of the T-cells (2), typically using a lentiviral or retroviral vector. Transduced cells express a CAR directed against a tumour antigen (3), and are expanded in
vitro in the presence of cytokines (4). Once CAR T-cell product release testing is complete, the patient received lymphodepleting (conditioning) chemotherapy (5), followed by
intravenous administration of CAR T-cells (6). The recipient is then monitored for toxicities.
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Table 1: Regulatory requirements for manufacture, release and delivery of CAR T-cell therapy in New Zealand.
Regulatory body Application to CAR T-cell therapy New Zealand legislation or guidance Standards to be met
Health and Approval required before conduct- Medicines Act 1981, the Guideline on the Regulation of Conduct according to CHMP† guidance document EMA/CHMP/
Disability Ethics ing CAR T-cell clinical trials. Therapeutic Products in New Zealand* IHC/135/95 Guideline for Good Clinical Practice E6(R2) to meet Interna-
Committee Standard Operating Procedures for Health and Disabil- tional Conference on Harmonisation Good Clinical Practice (IHC GCP)
(HDEC) ity Ethics Committees, v 2.0, August 2014 criteria.
Gene Technology As a cell therapy comprising Section 30 of the Medicines Act 1981 Demonstration of:
Advisory gene-modified cells, CAR T-cells • clinical benefit (or scientific rationale for potential benefit, if
Committee require GTAC approval. investigational)
(GTAC) ‡ • acceptable safety and toxicity data
• risk assessments and risk mitigation procedures in place
• if investigational, qualifications and experience of investigators
suitable.
Māori Consent and equity of access. Te Ara Tika Guidelines for Māori research ethics, Health Equity of access to therapy, including for those living distant from treat-
consultation Research Council New Zealand ment centres.
Māori consultation is an ethical
and legislative requirement for Ministry of Health document- Equity of Healthcare for Consent to treatment, including consent to cell shipment and storage,
research carried out within New Māori: A framework and future use of tissue.
Zealand’s district health boards .
The Treaty of Waitangi Māori consultation processes for research vary regionally.
Guidance about consent with respect to the Human
Tissue Act
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Table 1: Regulatory requirements for manufacture, release and delivery of CAR T-cell therapy in New Zealand (continued).
Regulatory body Application to CAR T-cell therapy New Zealand legislation or guidance Standards to be met
Environmental Approval required to: Hazardous Substances and New Organisms (HZNO) • Demonstrate satisfactory containment level in place to prevent
Protection • manufacture CAR T-cells, Act 1996, Section 40 escape of the GMOs into the environment.
Authority (EPA) classified as GMOs (geneti- • Demonstrate negligible risk of GMO forming a self-sustaining popu-
cally modified organisms) in lation outside of containment when released.
containment • Ensure necessary controls to mitigate potential risk are in place to
• release CAR T-cells from release GMO from containment.
containment to treatment
delivery site and to clinical
laboratory for safety testing.
Medsafe License to manufacture cell thera- PIC/S§ Ensuring the manufacturing facility and manufacturing procedures (in-
py product (pack, label and sell by cluding batch manufacturing records and product release criteria) meet
Guide for Good Manufacturing Practice for Medicinal
wholesale). Good Manufacturing Practice (GMP) standards.
Products, annexes 13 and 14
Licenses the New Zealand Blood Leukapheresis service audited against the code of GMP.
Service to collect and manufacture
therapeutic cells by apheresis.
*Under this legislation all clinical trials in New Zealand must receive HDEC approval.
†CHMP (The Committee for Medicinal Products for Human Use) is the European Medicines Agency’s (EMA)
committee responsible for human medicines.
‡ A committee maintained by the Health Research Council (HRC) of New Zealand to consider applications
for trials involving gene or other biotechnology therapies.
§ PIC/S Pharmaceutical Inspection Convention Pharmaceutical Inspection Co-operation Scheme.
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assure safe release within the ENABLE health outcomes, and Māori consultation is
trial included rigorous product labelling, an ethical and legislative requirement16,17 for
shipping and traceability measures. The research carried out within district health
International Society of Blood Transfusion boards. Yet significant health inequities
(ISBT) standards recommend standardised exist. Māori are approximately 20% more
bar codes to allow blood products to be likely to develop cancer than non-Māori
shipped internationally with clear, unam- and are twice as likely to die from cancer,14
biguous labelling and help to overcome including from non-Hodgkin lymphoma.15
language barriers.13 Furthermore, there These inequities are driven by delays in
are stringent procedures for packaging, diagnosis and treatment, worse access to the
transport, administration and disposal. wider determinants of health and inequities
Rigorous identity checks using inde- embedded in health system design.
pendent patient and product identifiers Cancer research has the opportunity to
are performed and recorded on designated contribute to Māori health advancement.
forms, to ensure the “chain of custody” The Health Research Council (HRC) of
is maintained and that the right patient New Zealand has implemented the Māori
receives the right product. Unused CAR Health Advancement Guidelines, which
T-cell vial(s) are returned to the manufac- require meaningful collaboration, consul-
turing facility for safe disposal. tation and partnership with Māori at the
The number and expansion of T-cells research design stage.16 Māori expertise
varies widely between patients, so the within the research team is recommended to
manufacturing facility often has an excess ensure the research results in Māori health
of lymphocytes and/or CAR T-cells following advancement and that tikanga Māori (Māori
product manufacture. Some cells must be processes and protocol) is valued in the
retained for quality control purposes, and research design and the sharing of results.
unless made available for future research This framework provides an excellent
(which requires proper consent), the resource for all health research conducted
remaining cells are typically destroyed. in Aotearoa New Zealand.
For our own CAR T-cell trial (ENABLE), we If access were equitable, investigational
seek consent to store unused cells within an CAR-T cell therapies within Aotearoa New
Immune Tissue Bank. This tissue bank was Zealand would provide an opportunity
formed with input from Māori researchers, for Māori to benefit from treatments that
and its governance group includes Māori are not publicly funded and that would
representation. At present, unused CAR otherwise be cost prohibitive. Māori, who
T-cells cannot be returned to their recipient regard genetic material as tapu (sacred/
or to the recipient’s whānau due to the restricted), may be concerned with
cell’s legal status as a GMO, although it is the application of genetic engineering.
our opinion that this might be possible in a However, where there are direct health
domestic CAR T-cell manufacturing facility benefits for Māori, and provided that these
in future, with appropriate risk assessment benefits are well communicated, many
and controls. will be supportive of this application.11,17 A
Table 1 summarises the agencies involved Māori consultation process is essential for
in regulating CAR T-cell manufature, release CAR T-cell research and standard of care
and delivery in New Zealand. delivery, and this should include devel-
opment of educational materials for Māori,
CAR-T cell therapies and equity their whānau and their clinicians.
for Māori For our own trial (ENABLE), Māori consul-
In Aotearoa New Zealand, Māori are tation was sought at an early stage during
afforded the right to equitable health protocol development. In order to address
outcomes under Te Tiriti o Waitangi and issues relating to Māori involvement and
ethical obligations under the United Nations recruitment and contribute to Māori health
Declaration on the Rights of Indigenous development, our CAR T-cell researchers
Peoples. Clinicians in New Zealand have an met with Research Advisory Group Māori
obligation to consider the degree to which (RAG-M) at Capital and Coast District Health
they can contribute to improving Māori Board (CCDHB) and Te Urungi Māori, the
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Māori steering group at the Malaghan The CARTOX group was also consulted
Institute. Following consultation, a brief regarding CAR T-cell toxicity education and
patient-focussed summary, in both English training material for clinical staff. Since
and te reo Māori, and a visual represen- commencing the ENABLE trial, the CARTOX
tation of the CAR T-cell treatment process group have met at least every six months in
(Figure 1) were incorporated into the order to review CAR T-cell-related toxicities
participant information and consent form. reported in the ENABLE trial and to evaluate
ENABLE participants are able to donate up-to-date published guidance on CAR T-cell
tissue to an Immune Tissue Bank, and we toxicity management. This has led to modifi-
have consulted with our (Māori) Tissue cations of both CRS and ICANS management
Bank Manager at the Malaghan Institute pathways as well the production of a
regarding tissue retention and karakia working document reviewing the evidence
arrangements. We collaborated with a for second-line management of severe CAR
Māori clinician and researcher familiar T-cell-related toxicities. Given our early
with managing patients with haemato- experience and feedback from interna-
logical malignancies. To reduce the risk that tional CAR T-cell treating clinicians and , we
distance from the treatment centre impedes recommend implementation of a CARTOX
study access, an agreement was reached group (or similar) for other centres adminis-
with a national cancer charity to support tering CAR T-cell therapies.
the travel costs for study participants and a
CAR T-cell toxicity education
family member, if they were not eligible for
To safely deliver CAR T-cell therapy,
the National Travel Assistance Scheme.
clinical teams must be trained in the
recognition and management of CAR
Clinical delivery of T-cell-related toxicities. For commercial
CAR T-cell therapy products, specific risk evaluation and miti-
gation strategies (REMS) may be required
CAR T-cell toxicity working group by the manufacturer, which are likely
CAR T-cell therapies can cause specific to involve product-specific training and
toxicities, particularly cytokine release knowledge assessments for specific clinical
syndrome (CRS) and immune effector staff.21 Training typically encompasses
cell-associated neurotoxicity syndrome areas such as prescribing, dispensing and
(ICANS; neurotoxicity).18 The consensus administering CAR T-cells and monitoring
guidelines for the diagnosis and grading of for, recognising and treating CAR T-cell
CRS and ICANS published by the American related toxicities.21 For the ENABLE Trial,
Society for Transplantation and Cellular we developed an educational tool and
Therapy (ASTCT) can be readily applied in competency assessment for clinical staff in
New Zealand hospitals.19 Consensus recom- our inpatient and day-ward areas and for
mendations for the management of CRS and members of the Patient at Risk and intensive
ICANS are also available.18,20 care teams. Regular educational updates are
For the ENABLE trial, we convened a CAR held. One-page CRS and ICANS “quicksheets”
T-cell toxicity (CARTOX) working group, were produced, and are displayed promi-
which included representatives from nently in the clinical area in which a CAR
haematology, neurology, intensive care, T-cell recipient is being treated.
immunology and nursing. The CARTOX
Availability of anti-cytokine therapy
group developed and reviewed CRS and
The hallmark of CRS is fever caused by
ICANS recognition and management
high levels of interleukin-6 (IL-6) during
pathways, based on consensus recommen-
CAR T-cell recognition of, and activation by,
dations18 and advice from experts in the
tumour cells. Tocilizumab, a monoclonal
field (Neelapu and Turtle, personal commu-
antibody against the IL-6 receptor, is highly
nications). These management pathways
effective for management of CRS and can be
have been posted on the hospital intranet
useful for ICANS.20 Although tocilizumab is
at the CAR T-cell treating site, with clear
not licensed by Medsafe in New Zealand for
paper-based management algorithms being
the treatment CAR T-cell therapy toxicities,
available for easy reference on the haema-
it is registered by the US Food and Drugs
tology ward where patients are treated.
Administration (FDA) for this indication22
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and is universally recommended in interna- T-cell treatment centre. After 3–4 weeks,
tional guidelines for CRS and ICANS.18,20 The most CAR T-cell recipients will be able to
REMS strategy for axicabtagene ciloleucel return to a home further afield. Recipient
requires that at least two doses of tocili- education is key. Because their primary and
zumab are available on site for each patient secondary care clinicians may lack CAR
when they are treated.21 Tocilizumab was T-cell experience, recipients should also
alraedy approved for treating paediatric receive clear and accurate information to
Acute Lymphoblastic Leukaemia (ALL) trial pass on to other healthcare professionals
participants, so a clinician-led application to they may meet.28 For the ENABLE Trial, CAR
PHARMAC was made in order to extend this T-cell recipients are given a wallet emer-
existing approval to include ENABLE trial gency card and a discharge summary sheet
participants. This application was successful, (Supplementary Materials).
and PHARMAC will now fund up to three
Cellular therapy registries
doses of tocilizumab to treat CRS and/or
As CAR T-cells are a relatively new
ICANS in ENABLE trial participants.23 In our
treatment modality, there is a possibility
opinion, emergency availability of anti-IL-6
that low incidence or late onset toxicities
therapies will need to be assured for future
will emerge, such as second malignancies
investigational or commercial CAR T-cell
or adverse pregnancy outcomes. Cellular
therapies in New Zealand. High-dose cortico-
therapy registries provide an important
steroids are used for severe CRS and ICANS;
framework for long-term follow-up and
there are no restrictions on the use of these
detection of such risks.29 The Center for
in New Zealand.
International Blood and Marrow Transplant
Expert opinion, preclinical data and Research (CIBMTR), to which New Zealand
case reports have recommended anakinra, stem cell transplant centres already report
siltuximab and dasatanib as second-line safety and efficacy data following stem cell
treatments for severe CRS or ICANS.24–26 transplantation, opened its Cellular Ther-
Although there are no definitive recom- apies Registry in June 2016, which aims to
mendations on which second-line agent to standardise CAR T-cell toxicity reporting
use first, many sites use anakinra (a human and data collection.29 Participation in the
intereukin-1 receptor antagonist) in this CIBMTR Cellular Therapies Registry is open
setting because pre-clinical studies have to CAR T-cell treatment centres worldwide,
suggested that IL-1 plays a crucial role in provided ethical approval for data collection
the pathogenesis of CRS and neurotoxicity, and sharing is in place. Within Australasia,
and because of anakinra’s clinical efficacy the Australian Bone Marrow Transplant
in similar settings, such as for macrophage Recipient Registry (ABMTRR) has recorded
activation syndrome (MAS), which can have outcomes of haematopoietic stem cell trans-
features that overlap with severe CRS.26,27 plantation since 1992 and has expanded
In conjunction with the CARTOX group, we its remit to collect data from CAR T-cell
developed contingency plans for second-line recipients.30
treatment of severe CRS or ICANS, which
included the study sponsor purchasing
a supply of anakinra to be stored at the
Challenges and
treatment site. opportunities
Patient education In many respects, New Zealand’s
Patients and their whānau need to receive healthcare system is well-suited to the
education about the potential adverse delivery of CAR T-cell therapies for haema-
effects of CAR T-cell therapy. As CRS and tological malignancies. Although our
ICANS are typically early toxicities, it is often regulatory processes are unique, they
recommended that patients remain close have been successfully tested for CAR
to the CAR T-cell treating centre, alongside T-cells through the ENABLE trial. The
a support person, for at least 21 days after New Zealand Blood Service (NZBS) runs a
CAR T-cell therapy.28 We provide in-person national network of blood collection and
and written education on CAR T-cell toxic- leukapheresis centres, and NZBS electronic
ities for recipients and their support person, systems and National Health Index (NHI)
as well as 24/7 contact details for the CAR numbers facilitate vein-to-vein traceability
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of transfused products, follow-up and the needed to address this are in place, and
recording of national healthcare alerts. some require strengthening. A network of
Clinical haematology services benefit from sites offering CAR T-cell therapies across
a national network of bone marrow trans- Aotearoa New Zealand will reduce travel
plantation centres, with established referral requirements for patients, but the nature of
pathways, and with comprehensive on-site CAR T-cell therapy means that most recip-
services, including intensive care, neurology, ients will have to spend time away from
immunology, infectious diseases, oncology home; travel and accommodation support
pharmacy and specialist laboratory services. will be essential. The need to travel is offset
Although commercial CAR T-cells are manu- by the one-off nature of CAR T-cell delivery
factured in large global hubs at present, and the fact that its principal toxicities occur
the capability to manufacture CAR T-cells early after administration.
within New Zealand will facilitate Māori Cost is a barrier to commercial CAR T-cell
engagement and guardianship and could therapies at present, and list prices for the
offer logistical advantages for CAR T-cell licensed autologous CAR T-cell products
delivery.31 Furthermore, future develop- axicabtagene ciloleucel and tisagenlecleucel
ments, such as outpatient management are high, at US$373,000 and US$475,000,
following CAR T-cell treatment and the use respectively.33 However, increasing compe-
of automated CAR T-cell product manufac- tition between manufacturers, negotiations
turing systems, may be means of lowering including schemes that link payment to
the cost of delivering treatment in New clinical response and the likely future
Zealand.32 availability of tocilizumab and anakinra
Equity of access is a key consideration biosimilars are expected to lower total
for all new therapies. Some mechanisms treatment costs in future. Pending funding
Table 2: Opportunities and challenges for CAR T-cell therapies in New Zealand.
Challenges Opportunities
Unique regulatory envi- Medsafe regulations are harmonised with EMA*; ENABLE trial provides
ronment regulatory experience
Logistics of cell harvest National leukapheresis & blood collection network (NZBS†); national pa-
and manufacturing tient identifiers (NHI‡); domestic CAR T-cell and lentiviral vector manufac-
turing capability (MIMR§; small-scale)
Equity of access Involve Māori in service planning; leverage national stem cell transplant
network; one-off CAR T-cell therapy possibly preferable to ongoing treat-
ments; inter-district funding and national travel assistance schemes
High cost of commercial CAR T-cells are a “one-off” rather than ongoing cost; declining costs due to
CAR T-cell therapies competition; clinical trial access pending commercial delivery; outpatient
administration can lower costs
Limited clinician ex- National network of stem cell transplant centres; clinical trial experience
perience of CAR T-cell of CAR T-cell delivery (ENABLE)
delivery
Restrictions on medicines Tocilizumab and anakinra biosimilars are in development; PHARMAC
used to treat CAR T-cell provides a national funding mechanism (“Special Authority”)
toxicities
* European Medicines Agency (EMA).
†New Zealand Blood Service (NZBS).
‡ National Health Index (NHI).
§ Malaghan Institute of Medical Research (MIMR
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of CAR T-cell therapies, clinical trials can programme in New Zealand, with particular
help bridge the gap in availability, at least consideration to Māori engagement and
for some patients, and prepare our regu- access to treatment. Having reviewed the
latory and clinical systems for routine CAR challenges and opportunities, we believe
T-cell delivery. Table 2 summarises key Aotearoa New Zealand is in an excellent
challenges and opportunities for CAR T-cell position to develop and implement both
therapies in New Zealand. investigational and commercial CAR T-cell
therapies in the future.
Conclusions
CAR T-cell therapy is shifting the treatment Supplementary
paradigm of relapsed and/or refractory
B-cell malignancies internationally. In this
material
• Supplementary Materia 1: CAR T-cell
viewpoint, we have outlined the regulatory
Wallet Emergency Card
processes and clinical preparations involved
in establishing the first CAR T-cell therapy • Supplementary Material 2: ENABLE
Trial Discharge Summary Sheet
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Competing interests:
RW, PG, TH and GG are employees of the Malaghan Institute of Medical Research,
which sponsors the ENABLE trial. The authors do not have proprietary or financial
interests in the WZTL-002 CAR T-cell product.
Acknowledgements:
The authors acknowledge funding support from the Health Research
Council of New Zealand (19/139 and 19/816), the Ministry of Business
Innovations and Employment, the LifeBlood Trust and Freemasons New Zealand.
This manuscript is dedicated to the memory of Dr John Carter.
Author information:
Robert Weinkove: Cancer Immunotherapy Programme, Malaghan Institute of
Medical Research, Wellington, New Zealand; Wellington Blood & Cancer Centre, Capital &
Coast District Health Board, Wellington, New Zealand; Department of Pathology & Molecular
Medicine, University of Otago Wellington, Wellington, New Zealand.
Philip George: Cancer Immunotherapy Programme, Malaghan Institute of Medical
Research, Wellington, New Zealand; Wellington Blood & Cancer Centre, Capital &
Coast District Health Board, Wellington, New Zealand.
Myra Ruka: Haematology Department, Waikato District Health Board, Hamilton,
New Zealand; Hei Āhuru Mōwai – Māori Cancer Leadership Aotearoa, Wellington,
New Zealand; Te Aho o Te Kahu – Cancer Control Agency, Wellington, New Zealand.
Tia Huia Haira: Cancer Immunotherapy Programme, Malaghan Institute of
Medical Research, Wellington, New Zealand; Clinical Human Immunology Laboratory,
Malaghan Institute of Medical Research, Wellington, New Zealand.
Giulia Giunti: Cancer Immunotherapy Programme, Malaghan Institute of Medical
Research, Wellington, New Zealand; Clinical Human Immunology Laboratory,
Malaghan Institute of Medical Research, Wellington, New Zealand.
Corresponding author:
Dr Robert Weinkove, Malaghan Institute of Medical Research, PO Box 7060, Wellington,
New Zealand, +64 4 499 6914 (phone), +64 4 499 6915 (fax)
Email: rweinkove@malaghan.org.nz
URL:
www.nzma.org.nz/journal-articles/chimeric-antigen-receptor-t-cells-in-new-zealand-chal-
lenges-and-opportunities
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