| 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 February 2024, the decision by the One Wales Medicines Assessment group was to retain the current advice with no changes required. This advice will be reviewed after two years or earlier if 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
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: 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: No updates to guidelines since last review.
Licensed alternative medicines or Health Technology Assessment advice for alternative medicines: NICE TA842: the appraisal of tisagenlecleucel (Kymriah®) for the treatment of adults with relapsed or refractory follicular lymphoma after two or more lines of systemic therapy was terminated due to absence of submission from the manufacturer, November 2022.
NICE TA894: axicabtagene ciloleucel (Yescarta®) is not recommended, within its marketing authorisation, for treating adults with relapsed or refractory follicular lymphoma after three or more lines of systemic therapy, June 2023.
Effectiveness: A repeat literature search conducted by AWTTC identified three studies relevant to the recommendation, one focussed on indolent lymphoma and two on Waldenström’s macroglobulinaemia (WM).
Suleman et al 2023 carried out a retrospective study using linked databases comparing a real-world cohort of bendamustine/rituximab (BR; n = 2032) with a historical cohort of a combined group (n = 2032) of rituximab with either cyclophosphamide, vincristine and prednisolone (R-CVP), or cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) for the first line treatment of indolent lymphoma. The results remain the same as those reported in the 2021 One Wales review as a conference abstract. The full study also reports on 5-year overall survival (OS; 80% BR versus 75% R-CVP/R-CHOP), where BR was associated with improved OS rates (hazard ratio [HR] 0.79; 95% CI: 0.69–0.91; p < 0.01). This trend was not consistent with elderly patients (> 75 years old; n = 824), for whom OS rates were comparable between treatments: 55.5% for BR (n = 401) and 55.4% for R-CVP/R-CHOP (n = 423; HR 0.97 95% CI: 0.78–1.21).
A systematic review and meta-analysis analysed the efficacy of first line treatment regimens for WM by evaluating pooled data from 11 phase II or phase III clinical trials (Chan et al. 2023). Sample size of the included studies ranged from 23 to 261. BR was associated with a higher or comparable response rate, OS and progression free survival (PFS) rate than comparators (Table 1).
Table 1. Pooled figures from 11 phase II or phase III clinical trials analysing bendamustine/rituximab in the treatment of Waldenström’s macroglobulinaemia
| Treatment | Response rate* | Overall survival (2 years) | Progression free survival (2 years) | Major response rate† |
| BR | 46% | 97% | 89% | 83% |
| BDRC | 33% | 94% | 81% | 85% |
| BBR | 47% | NR | 89% | 89% |
| IR | NR | 90% | 82% | 73% |
| BDR | 30% | 80% | 69% | 82% |
| R-CHOP | 25% | NR | NR | 91% |
| DRC | 15% | 91% | 69% | 81% |
| Bortezomib rituximab | 8% | NR | 66% | 66% |
|
BBR: bortezomib, bendamustine, rituximab; BDR: bortezomib, dexamethasone, rituximab; BDRC: bortezomib, dexamethasone, rituximab, cyclophosphamide; BR: bendamustine, rituximab; DRC: dexamethasone, rituximab, cyclophosphamide; IR: ibrutinib, rituximab; NR: not reported; R-CHOP: cyclophosphamide, doxorubicin, vincristine and prednisone *combining complete, near complete and very good partial response rates †combining complete, very good partial and partial response rates |
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The use of BR for WM was also analysed in a multicentre, retrospective study which focused on the effect of bendamustine dose on outcomes (Arulogan et al 2023). The results remain the same as those reported in the 2021 review as a conference abstract. As a first line treatment, those patients who received a higher bendamustine dose (≥ 1000 mg/m2 [n = 81] compared with those receiving 800-999 mg/m2 [n = 33]) were associated with superior major response rate (combining complete, very good partial and partial response) and PFS rate. Additionally, this trend was replicated among relapsed WM patients.
Safety: Suleman et al 2023 analysed the toxicity of BR (n = 2032) in comparison with R-CVP/R-CHOP treatment (n = 2032). BR was associated with higher incidences of hospital admissions for infection during an initial nine-month induction period (21.9% for BR versus 17.3% for R-CVP/R-CHOP; p < 0.01) and during the first three years (41.2% for BR versus 33.6% for R-CVP/R-CHOP; p < 0.01). BR was also associated with a higher mean number of emergency department visits during the initial nine months (1.01 ± 1.68 visits for BR versus 0.85 ± 1.51 visits for R-CVP/R-CHOP; p < 0.01). Over a three-year period, BR patients on maintenance therapy were more likely to be admitted for infection (37.9% for BR versus 31.5% for R-CVP/R-CHOP; p < 0.01). For both first line and maintenance therapy BR was associated with fewer admissions for neutropenia and febrile neutropenia than R-CVP/R-CHOP.
Cost-effectiveness: No relevant cost-effectiveness analyses were identified in the repeat literature search.
Budget impact: [CONFIDENTIAL DATA REMOVED] This is much lower than the original numbers estimated but 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: AWTTC has been provided with data for [CONFIDENTIAL DATA REMOVED].
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. [Confidential text removed]. 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: In 2 years
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) February 2024.
Copyright AWTTC 2024. 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 | February 2024 |
| Review schedule | Every 2 years |