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IMS 2025 | The potential of novel protein degraders to mitigate T-cell exhaustion in multiple myeloma
Karthik Ramasamy, MBBS, MRCP, FRCPath, PhD, Oxford University Hospitals NHS Foundation Trust, Oxford, UK, comments on the potential of novel protein degraders to mitigate T-cell exhaustion in multiple myeloma. Dr Ramasamy highlights that combining cereblon E3 ligase modulatory drugs (CELMoDs) with T-cell redirecting agents may enhance responses. This interview took place at the 22nd International Myeloma Society (IMS) Annual Meeting in Toronto, Canada.
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Transcript
T-cell exhaustion is a critical issue as we are using immune active therapies in multiple myeloma and there are two challenges with T-cell exhaustion. One is the response rates start to fall and resistance to these agents emerge and the second is increased risk of infections during T-cell exhaustion. We have a wealth of experience of using immunomodulatory drugs in the form of lenalidomide and pomalidomide for many years for the treatment of multiple myeloma...
T-cell exhaustion is a critical issue as we are using immune active therapies in multiple myeloma and there are two challenges with T-cell exhaustion. One is the response rates start to fall and resistance to these agents emerge and the second is increased risk of infections during T-cell exhaustion. We have a wealth of experience of using immunomodulatory drugs in the form of lenalidomide and pomalidomide for many years for the treatment of multiple myeloma. They work by modulating T-cell function. So what we’re eagerly looking forward to is the activity of CELMoDs in combination with these agents which use T-cell redirection for the treatment of multiple myeloma. I’m presenting some preclinical data which clearly shows that both iberdomide and mezigdomide enhance the ability of T-cells to attack the tumor and therefore we can start to look at this construct in clinical trials of combinations of CELMoDs with T-cell redirecting agents to induce deep remissions and longer remissions in patients as well as reduce the risk of infection.
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Disclosures
GSK: Consultancy, Research Funding, Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Sanofi: Consultancy, Research Funding, Speakers Bureau; Bristol Myers Squibb: Consultancy, Research Funding, Speakers Bureau; Amgen: Consultancy, Research Funding, Speakers Bureau; Adaptive Biotech: Consultancy, Speakers Bureau; Johnson and Johnson: Consultancy, Speakers Bureau; Menarini Stemline: Consultancy, Speakers Bureau; Pfizer: Consultancy, Speakers Bureau; Recordati rare Disease: Consultancy, Speakers Bureau.
