Research news // 17th December 2018
This week, results from the Myeloma XI trial evaluating the benefit of lenalidomide maintenance in newly diagnosed myeloma patients were published in the Lancet Oncology. The publication details the impact of lenalidomide maintenance therapy versus observation in newly diagnosed myeloma patients.
- Myeloma XI is the largest myeloma trial conducted and recruited over 4,000 patients
- Lenalidomide maintenance significantly increases remission time in newly diagnosed myeloma patients
- Patients who received lenalidomide maintenance after high-dose therapy and stem cell transplant had a significant increase in overall survival
- Lenalidomide maintenance was well tolerated
- Myeloma UK will work with all the stakeholders to push for the approval for the use of lenalidomide maintenance in the NHS.
“This was a significant trial which has delivered important data on the benefits of maintenance treatment with lenalidomide. Myeloma UK will be working with the company, drug approval bodies and with patients and their families on how access to maintenance treatment can be delivered to myeloma patients in the UK. This will be a challenging process. There are no maintenance treatments currently available for myeloma and proving cost-effectiveness will require flexibility, innovative thinking and commitment from all stakeholders. However, patients in the UK deserve access to the most effective new treatments, in line with best practice internationally and we will do all we can to ensure this is delivered.”
Shelagh McKinlay, Head of Patient Advocacy at Myeloma UK
What is Myeloma XI?
Myeloma XI is the largest trial ever conducted in myeloma and recruited over 4,000 patients across 110 NHS hospitals.
It looked at the benefits of different combinations and types of treatment in newly diagnosed myeloma patients focusing on the impact that this had on progression free and overall survival rates.
There were three variables in the study: induction treatment (cyclophosphamide, thalidomide with dexamethasone [CTD], cyclophosphamide, lenalidomide with dexamethasone [CRD] or carfilzomib with CRD [KCRD]); intensification treatment (cyclophosphamide, bortizomib with dexamethasone [CVD], no CVD or not randomised); and maintenance treatment (lenalidomide, lenalidomide & varinostat or no treatment).
Patients who received KRCD induction or lenalidomide and varinostat maintenance were not part of the data discussed in the Lancet Oncology publication.
This trial was funded Cancer Research UK, Celgene, Amgen, Merck Sharp and Dohme and Myeloma UK.
What is lenalidomide?
Lenalidomide, also known as Revlimid®, is an immunomodulatory drug (IMiD). Lenalidomide is chemically related to two other IMiDs used to treat myeloma called thalidomide and pomalidomide (Imnovid®).
Lenalidomide is licensed for use in combination with dexamethasone for myeloma patients. It is approved by the National Institute for Health and Care Excellence (NICE) for use on the NHS throughout the UK for patients who have had two prior treatments for their myeloma, have relapsed and require treatment. Lenalidomide is also approved in Scotland, Wales and Northern Ireland for certain subgroups of newly diagnosed patients. It is additionally approved for patients in Scotland who have had one prior treatment and have relapsed.
Lenalidomide is not currently available on the NHS as a maintenance treatment. Lenalidomide maintenance therapy following high-dose therapy and autologous stem cell transplantation in newly diagnosed patients is currently approved for use in Europe and USA.
What is maintenance?
Maintenance treatment is treatment administered long-term and intended to sustain control of the myeloma and reduce the risk of disease progression.
Result in Full
A total of 1917 patients, were randomised to receive either lenalidomide maintenance treatment or observation. Of these patients 1248 had received induction therapy followed by high-dose therapy autologous stem cell transplant and 723 had received only induction therapy. Lenalidomide maintenance significantly improved progression free survival (PFS) median PFS 39 months (95% CI 36–42) versus observation median PFS 20 months (18-22) (HR 0·46 [95% CI 0·41–0·53]; p<0·0001) of newly diagnosed myeloma patients irrespective of transplant status but did not improve 3-year overall survival (OS) was 78·6% (95% Cl 75·6–81·6) in the lenalidomide group and 75·8% (72·4–79·2) in the observation group (HR 0·87 [95% CI 0·73–1·05]; p=0·15).
Lenalidomide maintenance was well tolerated. Serious adverse events were observed in 45% of patients receiving lenalidomide maintenance and 17% in patients without lenalidomide. The most common adverse events reported were neutropenia (33%) and thrombocytopenia (17%). 14.7% (167/1097) patients receiving maintenance discontinued treatment due to adverse events and 4% discontinued due to patient preference.
The 3-year cumulative incidence of second primary malignancies was low, but higher in the lenalidomide group than the observation group (5·3% [95% CI 3·6–7·1] vs 3·1% [1·8–4·5]; HR 1·85 [95% CI 1·18–2·90].
A subgroup analysis of overall survival and transplant status showed a significant improvement in overall survival in transplantation-eligible patients treated with lenalidomide compared with those assigned to observation (HR 0·69 [95% CI 0·52–0·93]; p=0·014). However, lenalidomide maintenance therapy did not improve overall survival in transplantation-ineligible patients (HR 1·02 [95% CI 0·80–1·29]; p=0·88).
This further supports the use of lenalidomide maintenance after high-dose therapy and autologous stem cell transplant and is consistent with the previous trials and meta-analysis assessing the benefit of lenalidomide maintenance in transplant eligible patients.
However, it indicates that further work is required to understand why overall survival was not increased in transplant ineligible patients receiving lenalidomide maintenance versus observation. Exploratory analyses indicated that the factors determining transplant eligibility (e.g. age and fitness) could be contributing to the lack of overall survival benefit. This result is consistent with other trials and suggests that alternative approaches to improving overall survival in older patients are warranted.
The highly significant increase in progression free survival is a clear benefit and could improve the quality of life in patients and should be a key consideration when looking at the use of maintenance in all newly diagnosed myeloma patients.