| Status: Supported for use via the One Wales Medicines process | |
Bendamustine in combination with rituximab can be made available within NHS Wales for the treatment of previously untreated and relapsed follicular lymphoma, marginal zone lymphoma and Waldenstrom’s macroglobulinaemia under the following circumstances:
The risks and benefits of the off-label use of bendamustine plus rituximab for this indication should be clearly stated and discussed with the patient to allow informed consent. At the latest review of this recommendation in March 2026, the decision by the One Wales Medicines Assessment group was to retain the current advice with no changes required. This advice has been reviewed seven times by OWMAG since its issue in 2017 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 bendamustine ar y cyd â rituximab i drin rhai mathau o ganser y gwaed: lymffoma ffoliglaidd, lymffoma parth ymylol a macroglobwlinemia Waldenstrom. Dim ond os nad yw triniaethau trwyddedig yn addas y gellir rhoi bendamustine a rituximab, p'un a ydynt yn cael eu rhoi fel triniaeth gyntaf neu'n cael eu rhoi pan nad yw triniaethau eraill wedi gweithio.
Bydd bendamustine a rituximab 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 bendamustine a rituximab wedi'u trwyddedu i drin y mathau hyn o ganser y gwaed, felly os cânt eu defnyddio yn y modd hwn 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.
Am ragor o wybodaeth, ewch i: Lymphoma Action
What did the One Wales Medicines Assessment Group decide?
Bendamustine can be given in combination with rituximab to treat certain types of blood cancer: follicular lymphoma, marginal zone lymphoma and Waldenstrom’s macroglobulinaemia. Bendamustine and rituximab can only be given if licensed treatments are not suitable, whether they are given as a first treatment or given when other treatments have not worked.
Bendamustine and rituximab 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.
Bendamustine and rituximab are not licensed to treat these types of blood cancer so using them in this way 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 visit on these types of blood cancer visit: Lymphoma Action
Background: Bendamustine with rituximab is available in NHS England through clinical commissioning for the first line treatment of advanced, indolent non-Hodgkin’s lymphoma. Bendamustine is available through NHS England’s Cancer Drugs Fund for use in relapsed low-grade lymphoma, in people for whom standard treatment is unsuitable. According to the NHS England Cancer Drugs Fund criteria, bendamustine may be used in combination with rituximab, which is commissioned by NHS England for this indication.
A cohort of patients identified through data from individual patient funding request panels, and clinicians in Wales, confirmed there to be an unmet need within the service. This cohort included: young and fit people with aggressive, untreated and relapsed follicular lymphoma and marginal zone lymphoma, and Waldenström’s macroglobulinaemia for whom standard therapy is unsuitable. Based on this unmet need, this medicine combination was considered suitable for assessment via the One Wales process. Clinical experts consulted for this review supported the ongoing need for the option for use in NHS Wales for this cohort of patients.
Current One Wales decision: Supported with restrictions.
Licence status: Off-label use for this licensed medicine combination.
Guidelines: Two new guidelines have been published since the past review.
Lymphoma Study Association (LYSA) guidelines (2025) have been published for Waldenström’s macroglobulinemia (WM) recommending bendamustine and rituximab (BR) in combination for the management of newly diagnosed WM in fit patients with no TP53abn mutation. BR is also recommended for relapsed or refractory WM after first-line therapy for patients with contraindications to covalent Bruton’s tyrosine kinase inhibitors (cBTKi). Although no prospective studies directly compare the efficacy of different chemoimmunotherapy regimens, evidence supports BR regimen as producing the most profound responses, with the longest progression-free survival (PFS) and time-to-next-treatment. The guidelines also note that this regimen has been found to facilitate rapid disease control in highly symptomatic patients or those with large tumour masses.
British Society of Haematology guidelines (2023) have been published for the diagnosis and management of marginal zone lymphomas. These guidelines state that BR is effective for advanced stages of marginal zone lymphoma subtypes including extranodal marginal zone lymphoma or mucosa-associated lymphoid tissue, nodal marginal zone lymphoma and splenic marginal zone lymphoma. The guidelines also state that BR may be more toxic than other chemoimmunotherapy regimens.
Licensed alternative medicines or Health Technology Assessment advice for alternative medicines:
NICE TA892: mosunetuzumab (Lunsumio®) is not recommended for the treatment of adults with relapsed or refractory follicular lymphoma who have had two or more systemic therapies, May 2023
NICE TA1001: zanubrutinib (Brukinsa®) is recommended for the treatment of adults with marginal zone lymphoma after anti-CD20-based treatment, September 2024.
NICE TA1139: epcoritamab (Epkinly®) is recommended for treating relapsed or refractory follicular lymphoma after 2 or more lines of systemic treatment, March 2026.
NICE ID3726: the appraisal of odronextamab (Ordspono®) for the treatment of relapsed or refractory follicular lymphoma (FL) in adults is awaiting development.
Effectiveness: A literature search conducted by AWTTC identified one systematic review and eight studies published after this review that are relevant to the indicated recommendation. The studies are summarised in Appendix 1, results are in line with those reported in previous studies. As in previous reports, the three comparative studies demonstrate similar or improved outcomes for BR compared to rituxiumab with chemotherapy (including R-CHOP).
Ou et al (2023) published a systemic review and meta-analysis of BR versus R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone) for patients with indolent lymphoma. The six studies included in the final analysis have already been described in previous AWTTC external reviews (Rummel et al [2013], Flinn et al [2019], Cheah et al [2016], Olszewski et al (2020), Pouyiourou et al [2020] and Mondello et al [2016]). The overall conclusion of the meta-analysis was that the BR regimen had a better potential of prolonging PFS compared to R-CHOP (HR 0.67, 95% CI 0.46 to 0.97). Comparison of adverse event rates showed infection rates to be comparable between BR and R-CHOP (relative risk [RR] 0.75, 95% CI 0.52 to 1.08, p = 0.12). The risk of grade 3 and 4 hematologic toxicities seemed to be significantly lower with BR than with R-CHOP (RR range 0.38 to 0.62).
Quality of life data was reported for one of the studies included in the analysis (Flinn et al [2019)]). Patients treated with BR reported improvements in cognitive, physical, social, and emotional functioning, and global health status as well as a reduction in dyspnoea, constipation, and fatigue at least one-timepoint. Patients treated with R-CHOP reported less nausea or vomiting after 3 treatment cycles. Six cost effectiveness studies were reported in the analysis, all of which concluded that BR was a cost-effective alternative to R-CHOP, none of the studies were from a UK perspective and have therefore limited relevance to this review (Coyle, et al [2016], Dewilde et al [2014], Sabater et al [2016], Shoji et al [2019], Zhou et al [2017], Wehler et al [2015]).
Safety: No safety evidence was identified that was not in concordance with the well-known safety profiles of bendamustine and rituximab for this indication.
Cost-effectiveness: No relevant cost-effectiveness analyses were identified in the repeat literature search.
Budget impact: In the two years since the last review eight patients have received treatment with BR for indolent lymphomas in South East Wales. Extrapolating these figures to the population for all of Wales provides an estimate of approximately eight patients treated annually. This is considerably lower than the original estimate of 77 patients, however, this is consistent with patient numbers reported since the first review in 2018 which suggests an overestimate in the original report. In addition, there are more health technology-assessed treatment options available for indolent lymphoma since the original assessment in 2017. No further information on patient numbers has been provided on which to assess the budget impact.
Impact on health and social care services: Minimal.
Patient outcome data: Eight patients in South East Wales have received treatment with BR in the 2 years since the last review [confidential information 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: The clinical evidence presented supports the current use of bendamustine with rituximab as a treatment option in line with the current One Wales decision. Bendamustine in combination with rituximab for the treatment of indolent lymphomas should only be used in circumstances where other licensed and health technology appraisal-approved regimens are unsuitable.
Next review date: This advice has been reviewed annually by OWMAG since its issue in 2017 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. Bendamustine in combination with rituximab for the treatment of previously untreated and relapsed indolent lymphomas (OW08) March 2026.
Copyright AWTTC 2026. All rights reserved.
Medicine details |
|
| Medicine name | bendamustine and rituximab |
| One Wales decision status | Supported for use via the One Wales Medicines process |
| Reference number | OW08 |
| Decision issue date | March 2017 |
| Date of last review | March 2026 |
| Review schedule | No longer under review by OWMAG unless new evidence becomes available |