First quadruplet treatment for transplant-ineligible patients IsaVRD receives draft ‘no’ from NICE
The National Institute for Health and Care Excellence (NICE) have published draft guidance not recommending the use of isatuximab (Sarclisa®) in combination with bortezomib (Velcade®), lenalidomide (Revlimid®) and dexamethasone (IsaVRD) for newly-diagnosed myeloma patients who are not eligible for a stem cell transplant.
If approved IsaVRD would be the very first quadruplet treatment for people ineligible for a stem cell transplant. Around 3,300 patients could benefit from this treatment.
The MHRA approved the licence to treat newly-diagnosed transplant ineligible myeloma patients with IsaVRD in January 2025.
The licence approval was based on data from the Phase 3 IMROZ trial which compared IsaVRD to the triplet combination of bortezomib, lenalidomide and dexamethasone (VRD).
Although its appraisal committee agreed that IsaVRD was safe and effective, members felt they could not accurately assess whether the treatment would be cost-effective for the NHS.
Key challenges for evaluating the cost-effectiveness of IsaVRD include the lack of trial data comparing IsaVRD to daratumumab, lenalidomide and dexamethasone (DRD) and the immaturity of the trial data, with median progression-free survival having not been reached in the IsaVRD arm and overall survival having not been reached in both trial arms. To help address this the committee asked for further results from a network meta-analysis versus DRD.
The committee also requested further information about the impact on quality of life after the treatment is stopped.
NICE is expected to review its decision in July following consultation on the draft guidance.
Over the coming weeks, Myeloma UK will work with clinicians and patients to gather further evidence to be submitted to NICE and continue to make the case for IsaVRD to be rolled out on the NHS.
Shelagh McKinlay, Director of Research and Advocacy at Myeloma UK, said:
“While this news is very disappointing, it is important to remember that NICE’s decision is not final. The approval process can be lengthy, and it is not unusual for treatments to go through at least two appraisal committees before they’re made available on the NHS.
As the first quadruplet combination for transplant-ineligible patients, IsaVRD could make the difference for thousands of patients. Not only does it use four separate drugs to attack myeloma cells in different ways but it also offers more flexibility to manage side effects.
We firmly believe people with myeloma should have access to IsaVRD and we are doing everything we can to get this treatment across the line.
Until we have a cure, it is absolutely vital that all patients are given as many options to control their disease as possible.”
Q&A
What is a draft recommendation?
A draft recommendation is not a final a decision from NICE. Draft recommendations are published if NICE decides more evidence is needed to recommend the new treatment for use on the NHS.
This can either be because NICE needs more data or because there are concerns about the cost-effectiveness of the new treatment.
Publication of a draft recommendation gives the pharmaceutical company, clinicians and patients the chance to submit further evidence or information about the new treatment to inform the final decision.
What happens next?
Myeloma UK and all other interested parties have until 19 June to submit further evidence. A second committee meeting will then be held on 2 July.
Why did NICE say no?
NICE recognised that IsaVRD is safe and effective for the treatment of newly-diagnosed myeloma patients. However, the committee said it needed further data to confirm how well IsaVRD works compared to available treatment options and, ultimately, whether IsaVRD is a cost-effective use of NHS resources.
The price of drugs is a factor in NICE decisions, but it is important to bear in mind that the committee does not look at whether a drug is expensive. Rather, it looks at whether it is cost-effective compared to the current standard of treatment.
What is IsaVRD?
IsaVRD is a combination of three drugs: isatuximab, bortezomib, lenalidomide and dexamethasone.
Isatuximab belongs to a group of drugs known as monoclonal antibodies. It works by harnessing the body’s immune system.
It is a synthetic antibody designed to target myeloma cells by detecting a protein commonly found on the surface of myeloma cells called CD38. When it finds and attaches to CD38, it makes the myeloma cell more visible to the immune system. It helps the patient’s immune system locate and kill myeloma cells.
Isatuximab is currently used in combination with pomalidomide (Imnovid®) and dexamethasone (IsaPD) to treat myeloma patients who have had three previous lines of treatment, including lenalidomide and a proteasome inhibitor, and whose myeloma has progressed on their last treatment.
What about patients in Scotland, Wales and Northern Ireland?
In Scotland, the Scottish Medicines Consortium makes decisions about which treatments to fund through the NHS. The SMC has not started an appraisal of IsaVRD yet. We hope it will start later this year.
In Wales, decisions about which treatments to fund through the NHS are made by the All Wales Medicines Strategy Group (AWMSG) and NICE.
In Northern Ireland, the Department for Health makes decisions on which treatments to fund through the NHS. It can follow guidance issued by either NICE or the SMC but usually follows the guidance issued by NICE.
Useful resources
- NICE draft guidance: Isatuximab in combination for untreated multiple myeloma when a stem cell transplant is unsuitable
- MHRA: Isatuximab summary of product characteristics (SPC)
- MHRA: Isatuximab patient information leaflet (PIL)
- MHRA: Bortezomib summary of product characteristics (SPC)
- MHRA: Bortezomib patient information leaflet (PIL)
- MHRA: Lenalidomide summary of product characteristics (SPC)
- MHRA: Lenalidomide patient information leaflet (PIL)
- MHRA: Dexamethasone summary of product characteristics (SPC)
- MHRA: Dexamethasone patient information leaflet (PIL)
