Recommendations for research

The Guideline Committee has made the following recommendations for research. The Committee's full set of research recommendations is detailed in the full guideline.

1 Diagnostic investigations to predict treatment outcomes

What is the prognostic value of the Hevylite assay and ratio compared with other prognostic factors and tests, including the serum‑free light‑chain assay and fluorescence in‑situ hybridisation (FISH), in people with newly diagnosed myeloma who are starting treatment?

Why this is important

Hevylite is a new assay that some studies have indicated is a useful prognostic tool. However, it is not clear how robustly it has been evaluated against other prognostic factors and tests, or whether it is an independent prognostic factor. The Hevylite assay should be evaluated in an accredited centralised laboratory independent of links with the manufacturer. Outcomes of interest are overall response, complete response, minimal residual disease, progression‑free survival, overall survival and resource use.

2 Imaging investigations for newly diagnosed myeloma

What is the comparative effectiveness of whole‑body MRI, fluorodeoxyglucose positron emission tomography CT (FDG PET‑CT) and whole‑body low‑dose CT in detecting lesions that may determine the start of treatment for people with newly diagnosed myeloma?

Why this is important

Newer imaging techniques are replacing skeletal surveys for assessing myeloma‑related bone disease in people with newly diagnosed myeloma. However, the most effective technique is not known. Outcomes of interest are lesion detection, sensitivity and specificity for myeloma‑related bone disease, patient acceptability, incremental upstaging, radiation exposure, risk of second primary cancer, the impact of additional information on predicting progression‑free survival, overall survival and skeletal‑related events.

3 Management of smouldering myeloma

Which combinations of FISH, molecular technologies, bone marrow plasma cell percentage, whole‑body imaging, immunophenotype, serum‑free light‑chain levels or ratio, Hevylite, paraprotein levels, immunoparesis, and International Staging System (ISS) are most effective at risk stratification for people with smouldering myeloma?

What is the comparative effectiveness of fixed duration treatment (with or without bone‑directed therapy), continuous treatment (with or without bone‑directed therapy) and no treatment (with or without bone‑directed therapy) for people with smouldering myeloma?

Why this is important

Changes to the International Myeloma Working Group definitions of smouldering myeloma and myeloma have affected the risk stratification process for smouldering myeloma. It is unclear if the previous risk stratification approach remains valid. It is also unclear if earlier treatment will be of benefit to people with smouldering myeloma. This study should be a randomised multi‑centre prospective trial for patients with newly diagnosed smouldering myeloma (as defined by the International Myeloma Working Group 2014 classification). Outcomes of interest are time to biochemical and/or clinical progression, overall survival, adverse events, quality of life and resource use.

4 Allogeneic stem cell transplantation

What is the effectiveness of combined autologous–allogeneic stem cell transplantation compared with autologous stem cell transplantation, plus consolidation and maintenance treatment in chemosensitive patients at first response or first relapse?

Why this is important

There are conflicting data from a small number of studies on long‑term survival following auto/allo stem cell transplantation compared with autologous stem cell transplantation. These studies were performed before thalidomide, bortezomib and lenalidomide were used as myeloma treatments. These drugs produce better responses and also have the capacity to affect immunological responses after the transplant. Research is needed to see if there is a role for auto/allo stem cell transplant in the ongoing treatment of myeloma. Outcomes of interest are progression‑free survival, overall survival, transplant‑related mortality, quality of life, early and late toxicity including graft‑versus‑host‑disease (GvHD) and resource use. This research should be included as an option in appropriate mainstream clinical trials for myeloma.

5 Bisphosphonates for the prevention of bone disease

What is the effectiveness of monthly zoledronic acid given indefinitely compared with zoledronic acid given for a fixed duration in patients with myeloma?

Why this is important

There is good‑quality evidence to support the use of zoledronic acid to prevent bone disease in people with myeloma. However, the optimal frequency and duration of treatment is not clearly defined and needs further research, particularly given the quality‑of‑life implications for people needing regular, life‑long visits to hospital. This study should be a randomised controlled trial. Outcomes of interest are skeletal‑related events, progression‑free survival, overall survival, utility of bone biomarkers, incidence of osteonecrosis of the jaw, quality of life and resource use.

  • National Institute for Health and Care Excellence (NICE)