| Status: Supported for use via the One Wales Medicines process | |
Using the agreed starting and stopping criteria, azacitidine can be made available within NHS Wales for the treatment of progressive angioimmunoblastic T-cell lymphoma. The risks and benefits of the off-label use of azacitidine for this indication should be clearly stated and discussed with the patient to allow informed consent. Providers should consult the relevant guidelines on prescribing unlicensed medicines before any off-label medicines are prescribed. This recommendation has been endorsed by the All Wales Medicines Strategy Group (AWMSG) and ratified by Welsh Government. This advice has been reviewed three times by OWMAG since its issue in 2020 with no new evidence identified to affect the current recommendation. Therefore, this advice will no longer undergo review by OWMAG unless new evidence becomes available. |
Darllen yn Gymraeg / Read in English
Beth benderfynodd Grŵp Asesu Meddyginiaethau Cymru’n Un?
Gellir rhoi azacitidine i drin math prin o ganser y gwaed a elwir yn lymffoma celloedd T angioimmunoblastic (AITL). Mae AITL yn fath o lymffoma nad yw’n lymffoma Hodgkin sy'n tyfu’n gyflym ac sy’n digwydd pan fydd celloedd T yn y gwaed yn mynd yn annormal.
Bydd azacitdine ar gael i gleifion cymwys sydd wedi cofrestru gyda phractis meddyg teulu yng Nghymru, hyd yn oed os oes angen iddynt dderbyn eu triniaeth y tu allan i Gymru.
Nid yw azacitidine wedi'i drwyddedu i drin AITL, felly os caiff ei ddefnyddio i drin AITL fe’i gelwir yn ddefnydd “all-drwydded”. Pan gaiff meddyginiaeth ei defnyddio yn “all-drwydded”, rhaid i'ch meddyg esbonio'n glir i chi y risgiau a'r manteision o gymryd y feddyginiaeth. Dylai eich meddyg roi gwybodaeth glir i chi, siarad â chi am eich opsiynau a gwrando'n ofalus ar eich barn a'ch pryderon. Darllenwch ein taflen wybodaeth i gleifion am ddefnydd di-drwydded ac all-drwydded o feddyginiaethau.
Mae Grŵp Asesu Meddyginiaethau Cymru'n Un ac AWTTC yn adolygu'r penderfyniad hwn yn rheolaidd i weld a oes unrhyw dystiolaeth newydd a allai effeithio ar y penderfyniad hwn.
I gael rhagor o wybodaeth am AITL ewch i wefan Macmillan: Angioimmunoblastic T-cell lymphoma (Saesneg yn unig)
What did the One Wales Medicines Assessment Group decide?
Azacitidine can be given to treat a rare type of blood cancer called angioimmunoblastic T-cell lymphoma (AITL). AITL is a fast-growing type of non‑Hodgkin lymphoma that happens when T-cells in the blood become abnormal.
Azacitidine will be available to eligible patients who are registered with a GP practice in Wales, even if they need to receive their treatment outside Wales.
Azacitidine is not licensed to treat AITL, so using it to treat AITL is called “off-label” use. When a medicine is used “off-label”, your doctor must clearly explain to you the risks and benefits of taking the medicine. Your doctor should give you clear information, talk with you about your options and listen carefully to your views and concerns. Read our patient information leaflet about unlicensed and off-label use of medicines
The One Wales Medicines Assessment Group and AWTTC review this decision regularly to see if there is any new evidence that may affect this decision.
For more information about AITL visit the MacMillan website: Angioimmunoblastic T-cell lymphoma
Starting criteria: Second and subsequent line therapy of patients with relapsed/refractory angioimmunoblastic T-cell lymphoma (AITL) that are not fit or suitable for intensification of therapy with a BEAM (carmustine [BCNU], etoposide, cytosine arabinoside [Ara-C] and melphalan) conditioned autograft. Azacitidine should only be considered if the patient is ineligible to enrol in a clinical trial.
Patients who satisfy the eligibility criteria will be prescribed azacitidine following consultation with the patient and/or carer taking into account potential adverse effects, cautions and contraindications. This consultation should be recorded in the patient’s notes.
Azacitidine is prescribed at a dose of 75 mg/m2, injected subcutaneously, daily for 7 days followed by a 21 day rest period. It may be appropriate to administer this treatment as 5 days on, weekend off, 2 days on, to avoid higher administration costs over the weekend.
The Cheson criteria is used to classify AITL response to treatment, the treatment goal is remission1. In summary, a complete response (CR) is defined as the disappearance of all evidence of disease, a partial response (PR) is a regression of measurable disease and no new sites. Stable disease (SD) is a failure to attain CR/PR or progressive disease (PD). PD or relapsed disease is an increase by ≥ 50% of measurable signs of the disease from nadir. Overall response rate represents both CR and PR1.
Prescribers will be expected to provide outcome data on all patients who receive azacitidine treatment under the One Wales Medicines process.
Stopping criteria: Treatment should be reviewed after three cycles and azacitidine stopped if any of the following criteria are met:
At 12 months treatment should be reviewed to consider whether there is continued clinical benefit for the patient and no evidence of disease progression.
Reference:
Health boards will take responsibility for implementing One Wales Medicines Assessment Group decisions and ensuring that a process is in place for monitoring clinical outcomes.
Background: Angioimmunoblastic T-cell lymphoma (AITL) is a rare and often aggressive form of peripheral T-cell lymphoma. Signs and symptoms include generalised lymphadenopathy, skin rash, arthritis, polyclonal hypergammaglobulinemia and autoimmune conditions such immune thrombocytopenia. Typical frontline therapy is CHOP-like (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy, followed by BEAM (carmustine [BCNU], etoposide, cytosine arabinoside [Ara-C] and melphalan) conditioned autograft. AITL patients commonly relapse, and not all patients are eligible for BEAM conditioned autograft. Clinicians in Wales therefore considered there was an unmet need for the subset of relapsed or refractory patients not suitable or unfit for BEAM. This medicine was therefore considered suitable for assessment via the One Wales Medicines process.
Current One Wales decision: The subcutaneous formulation of azacitidine is supported for use for this indication.
Licence status: Azacitidine is not licensed to treat progressive (relapsed or refractory) AITL; its use in this indication is off-label. AWTTC is not aware of any plans to pursue marketing authorisation of subcutaneous azacitidine for this indication at this time. The manufacturers of oral azacitidine are not pursuing a licence for this indication in the UK.
Guidelines: Updated European guidelines for systemic T-cell lymphomas (d’Amore et al. 2025) include angioimmunoblastic T-cell lymphoma (AITL) under the T follicular helper phenotype (TFHL) subgroup. For relapsed/refractory disease, the guideline notes that cyclosporin A, lenalidomide, and azacitidine have demonstrated efficacy. The guideline cites the phase III ORACLE trial as supportive of azacitidine’s potential role in selected patients with TFHL.
Licensed alternative medicines or Health Technology Assessment advice for alternative medicines: No new medicines or Health Technology Assessment advice reported.
Effectiveness: AWTTC conducted a literature search in October 2025 to find new evidence for the use of azacitidine for the treatment of progressive AITL. The search excluded articles published before 2024, articles that reviewed evidence previously presented in AWTTC’s first Evidence Summary Report (2020), and conference abstracts.
The search identified one open-label, randomised, phase 3 study (ORACLE) which evaluated oral azacitidine compared with standard therapy in adults with relapsed or refractory TFHL. The study’s results were previously reported in the last review from a conference abstract and have now been verified in a peer-reviewed publication. Oral azacitidine was associated with prolonged overall survival and a favourable safety profile compared with standard care. However, it did not meet the primary outcome of the study, progression-free survival, this may be due to the study being underpowered. No papers for subcutaneous azacitidine were identified in the literature search.
Safety: Safety analyses from the ORACLE trial indicated a more favourable profile for azacitidine. Grade 3–4 adverse events occurred in 76% of patients receiving azacitidine versus 98% in the standard therapy group (gemcitabine, bendamustine or romidepsin), serious adverse events occurred in 26% versus 44% of patients respectively. The most common grade 3 or worse events were haematologic toxicities, infection and gastrointestinal toxicities. Haematologic toxicity was reported in 67% of azacitidine-treated patients compared with 93% in the standard therapy arm. Infection rates were lower with azacitidine (19% versus 33%), while gastrointestinal events were slightly higher (12% versus 2%). Treatment-related deaths occurred in two patients (one endocarditis and one candidiasis) in the azacitidine group and three in the standard therapy group (one heart failure, one COVID-19 and one cause unknown).
Cost-effectiveness: No relevant cost-effectiveness analyses were identified in the repeat literature search.
Budget impact: The original Evidence Status Report estimated an eligible population of approximately five patients per year in Wales. Since the last review in 2023, real-world outcome data provided by clinicians working in Wales indicate that five patients have received treatment in south Wales. The current price of generic azacitidine has significantly decreased under the All Wales Drug Contract. Specifically, azacitidine 100 mg subcutaneous 1 ml vial injection is now priced at [confidential text removed], whereas the original budget impact calculations were based on a price of [confidential text removed]. This change will result in a significant reduction in the budget impact for this treatment.
Impact on health and social care services: No new impact data have been provided, though we consider the impact of this medicine to be minimal.
Patient outcome data: Five patients from South Wales have received azacitidine for relapsed or refractory AITL spanning a data period of two to five years. [confidential text removed]. Clinicians note the limited usage of this treatment in Wales but would value its continued availability through One Wales when treatment is required.
Evaluation of evidence: Since the last review in 2023 no new clinical data regarding the use of azacitidine for the treatment of progressive angioimmunoblastic T-cell lymphoma have been identified. The contract price for generic azacitidine is significantly lower than previous estimates, delivering a notable reduction in the budget impact.
Clinicians have reported outcomes for five patients that have been treated in South Wales spanning a period of 5 years; [confidential text removed]. The response rate is in line with the limited cases reported for this patient group in the literature. Patient numbers are lower than the original estimates of five patients across Wales per annum. Clinicians indicate that azacitidine remains a useful treatment modality for a small cohort of patients.
AWTTC recommends continuing to allow access in Wales to azacitidine as treatment for progressive angioimmunoblastic T-cell lymphoma.
Next review date: This advice has been reviewed three times by OWMAG since its issue in 2020 with no new evidence identified to affect the current recommendation. Therefore, this advice will no longer undergo review by OWMAG unless new evidence becomes available.
References: a full reference list is available on request.
Disclaimer: This document includes evidence published since the last review or full assessment of this medicine for the indication under consideration. It does not replace the original full evidence status report. Any previous reviews and the original full evidence status report are available from this webpage in the document history section.
Care has been taken to ensure the information is accurate and complete at the time of publication. However, the All Wales Therapeutics and Toxicology Centre (AWTTC) do not make any guarantees to that effect. The information in this document is subject to review and may be updated or withdrawn at any time. AWTTC accept no liability in association with the use of its content. An Equality and Health Impact Assessment (EHIA) has been completed in relation to the One Wales policy and this found there to be a positive impact. Key actions have been identified and these can be found in the One Wales Policy EHIA document.
Information presented in this document can be reproduced using the following citation: All Wales Therapeutics & Toxicology Centre. Evidence Review. Azacitidine for the treatment of progressive angioimmunoblastic T-cell lymphoma (OW16). 2026
Copyright AWTTC 2026. All rights reserved.
Medicine details |
|
| Medicine name | azacitidine |
| One Wales decision status | Supported for use via the One Wales Medicines process |
| Reference number | OW16 |
| Decision issue date | July 2020 |
| Date of last review | February 2026 |
| Review schedule | No longer under review by OWMAG unless new evidence becomes available |