MARo
Research type
Research Study
Full title
Bone Marrow Aspirates in Relapsed / Treatment Resistant Multiple Myeloma – Exploiting Metabolic Vulnerabilities to Improve Treatment Response
IRAS ID
304232
Contact name
Philip Weir
Contact email
Sponsor organisation
Queen's University Belfast
Duration of Study in the UK
2 years, 1 months, 31 days
Research summary
SUMMARY OF RESEARCH
Multiple myeloma (plasma cell myeloma) is a haematological malignancy characterised by clonal plasma cell proliferation in the bone marrow. Numerous treatments are now available, but multiple myeloma remains incurable and follows a relapsing remitting pattern with each subsequent line of treatment typically being less effective than the previous as the disease develops resistance. New strategies are required to extend these periods of disease control and reduce resistance to existing effective therapies.
One way that many cancers develop treatment resistance is through alterations to their metabolism. This remains a relatively unexplored area in multiple myeloma research with significant scope for further study.
Patients with multiple myeloma usually get bone marrow aspirate and trephine biopsies taken at the time of initial diagnosis and the local biobank has many of these samples available for research. Multiple myeloma relapse is usually confirmed through testing of blood samples and repeat bone marrow biopsies are rarely performed at relapse. Due to their rarity, the biobank does not contain many relapsed / treatment resistant myeloma bone marrow samples.
To enable in vitro testing of drugs targeting metabolic changes in resistant multiple myeloma, methods of obtaining relapsed / treatment resistant myeloma bone marrow samples are necessary.
This study intends to help address this issue by providing a mechanism for the collection of bone marrow aspirate samples from patients with relapsed / treatment resistant multiple myeloma for use in in vitro testing of drugs targeting metabolic changes with the aim of overcoming or reducing treatment resistance. The bone marrow aspirates will be taken in Belfast City Hospital and in vitro testing will be carried out at Queen’s University Belfast.
SUMMARY OF RESULTS
Multiple myeloma is a blood cancer that can become resistant to important treatments called proteasome inhibitors. We looked at how the cancer cells change their energy use when they become resistant and tested many drugs to find new weaknesses.
What we did
We compared normal myeloma cells with cells that had become resistant to treatment. We measured how much energy they used and tested over 800 drugs to see which ones could kill the resistant cells. We also looked at patient data to see which genes change when the cancer comes back.What we found
Resistant cells were much more active and used more energy. We found 40 drugs that worked better on resistant cells, many of which targeted a protein called HIF 1α. This protein was also more active in patients when their cancer returned.Conclusion
HIF 1α may be an important new target for treating myeloma that no longer responds to current drugs. Further testing will help confirm which drugs are most effective.REC name
HSC REC A
REC reference
21/NI/0178
Date of REC Opinion
4 Jan 2022
REC opinion
Further Information Favourable Opinion