The National Institute for Health and Care Excellence (NICE, one of the bodies that decides whether to make drugs available on the NHS) has opened a consultation on its appraisal of chlormethine gel for the treatment of mycosis fungoides, a type of cutaneous (skin) T-cell lymphoma.
Chlormethine (also known as mechlorethamine or nitrogen mustard) is a type of chemotherapy that is applied directly to the skin (topical chemotherapy). It has been used to treat skin lymphoma for over 50 years. In the past, it was available as a lotion that had to be made up at home each day, or as an ointment that was prepared in specialised pharmacy departments. Chlormethine gel is a new, ready-made gel formulation.
In its draft recommendation, NICE suggests that chlormethine gel should not be made available on the NHS. However, this is not NICE's final guidance and these recommendations may change after consultation.
Lymphoma Action is among organisations and individuals opposing the recommendation and we hope this will result in a change of guidance.
The consultation runs until 26 August 2020 and is open to anybody who has an interest. Please let NICE know your views.
You will need to register with NICE to submit a response to the consultation. You might find some of the questions in the consultation difficult to answer. You are free to use Lymphoma Action’s response below as a basis for your answers if you would like to.
- We are concerned that clinical trial data and real-world experience supporting the use of chlormethine for mycosis fungoides (MF) has been unreasonably dismissed. Formulations of chlormethine have been used to treat skin lymphoma for over 50 years. Chlormethine ointment, the comparator in the main trial of chlormethine gel, was accepted as an effective treatment for MF in the UK from the 1980s and 1990s but its availability was limited nationally due to the need to prepare it for each patient in specialised pharmacy departments, causing an unacceptable health risk due to chemotherapy spillage. It has continued to be used in Manchester, UK, until recently. It is unfair to dismiss the clinical evidence supporting chlormethine gel on the basis that the comparator is no longer available in the UK. Chlormethine gel has been shown to be as effective as a previously accepted treatment but is far more convenient to prescribe and administer. It has been widely used internationally.
- We feel that the recommendation does not adequately address unmet needs for people with MF. It is baffling that the committee specifically acknowledges that there is a clinical need for chlormethine gel as an alternative treatment for people with MF but fails to recommend it for NHS funding. Notably in light of the COVID pandemic, where hospital footprints are being reduced and services such as phototherapy halted, an effective home treatment is highly desirable. As stated in the committee report, patients with early stage MF often have multiple courses of topical treatments, phototherapy or localised radiotherapy. If symptoms fail to respond to these treatments, systemic therapy becomes necessary. Having an additional effective, well tolerated and convenient topical treatment therefore has the potential to delay the need for systemic treatments – an option that would be welcomed by patients and would also reduce the burden on the NHS.
- We feel that too much emphasis has been placed on the fact that chlormethine gel is not curative. No early stage MF treatments are curative and all are given to reduce symptom burden and improve quality of life for symptoms, functions and emotions. The recommendation acknowledges that treatments for MF aim to relieve symptoms rather than cure the disease. Indeed, this is the case for the specified comparator agents. The committee also acknowledges in a statement that chlormethine gel is effective at relieving symptoms but does not seem to give this due consideration. Symptoms have a considerable impact on the day-to-day lives of patients and effective symptom control has the potential to significantly improve the quality of life of people affected by CTCL.
- We do not consider that the indirect benefits of an effective topical therapy have been adequately considered. Chlormethine gel is administered by the patient (or caregiver) in their own home without the need to travel for appointments. Obviously this relieves pressures on outpatient departments and treatment centres but it also reduces travel time and costs for patients and their carers – which can be significant when travelling to specialised centres that provide phototherapy – and reduces the need for people who are employed to take time off work. As well as improving quality of life, this has indirect economic benefits. In addition, unlike systemic therapies, chlormethine gel does not require patients to undergo blood test monitoring during treatment.
- We are concerned that the committee seems to have based cost-effectiveness on the ERG estimate of how much gel a “typical patient” would use per month rather than the lower estimates provided by clinical experts and the submitting company (based on real-world clinical experience and clinical trial data, respectively). There is no recognition that a topical at-home therapy reduces treatment times and sick leave from work that thrice weekly phototherapy visits to hospitals incur. The committee report states, ‘The resulting incremental cost-effectiveness ratio (ICER) was above what NICE considers a cost-effective use of NHS resources’ but there is no justification provided for using the ERG estimate in preference to other estimates. The committee states that there was ‘no direct evidence that the ERG estimate was incorrect’, but it does not provide direct evidence that the ERG estimate is correct. Neither does it provide direct evidence that the company or clinician estimates are incorrect, so it is difficult to comprehend why the committee has chosen ERG estimates above the others.
20 August 2020