COMy 2023 | Optimizing immunotherapy in myeloma: tumor profiling, mutations & characterizing T-cell fitness
Paola Neri, MD, PhD, University of Calgary, Calgary, AB, Canada, discusses approaches to improve immunotherapy for patients with multiple myeloma. Dr Neri first explains the importance of tumor profiling to ensure that the targets of a given immunotherapy are present, and further highlights the importance of identifying mutations which may impact the efficacy of an agent. Next, from an immunological perspective, Dr Neri explains the need to characterize T-cell fitness in patients, and notes that this could be enhanced with more extensive use of techniques such as single-cell assays and mass spectrometry. This interview took place at the 9th World Congress on Controversies in Multiple Myeloma (COMy) 2023, held in Paris, France.
These works are owned by Magdalen Medical Publishing (MMP) and are protected by copyright laws and treaties around the world. All rights are reserved.
Transcript (edited for clarity)
That is the million-dollar question, though. I’ll try to give you my input there. So I think to tailor immunotherapy right now, we need to think two components, of course, profiling the tumor because again, at the end of the day, we need to make sure the target is there and whole-genome sequencing, for example, will be a very useful tool, especially because apparently at the end of the year it will become cheaper and cheaper...
That is the million-dollar question, though. I’ll try to give you my input there. So I think to tailor immunotherapy right now, we need to think two components, of course, profiling the tumor because again, at the end of the day, we need to make sure the target is there and whole-genome sequencing, for example, will be a very useful tool, especially because apparently at the end of the year it will become cheaper and cheaper. So we need to profile the tumor and see if the target is there. I will add not only expression, but we need to see if there are mutations in the BCMA. We have data, we have shown already that there are certain mutations in the extracellular domain of BCMA that make patients resistant to T-cell engagers, so I think this is important for us to know. And of course in the immune part, of course the T-cells need to be interrogated. If T-cell exhaustion is present early on in this disease, even more in patients relapsing exposed to other therapy. So I think we are trying to identify a signature that can be helpful from a routine point of view to screen patients because I think the importance is because we have so effective therapy to know if that patient has a healthy T-cell phenotype or cells that are fit enough to be triggered and do the response. And I think with single-cell work, with mass spectrometry, we can probably learn this kind of approach. And in the future, I envision really discussing, interrogating both components: the tumor and immune cells to really identify if immunotherapy is the right call for a patient. Or maybe we should move on to another approach, a PI or IMiDs, and so on.
Read more...
