COMy 2022 | The future of myeloma treatment and the possibility of cure
In this video, Kenneth Anderson, MD, Dana-Farber Cancer Institute, Boston, MA, gives an overview of the future treatment of myeloma and his presentation at COMy 2022. Dr Anderson highlights his presentation which covered a variety of topics, including novel technologies used to monitor myeloma, the application of therapeutic agents, advances in immunotherapy, and novel targets. Dr Anderson then goes on to discuss precision medicine and the role of novel immunotherapies, including chimeric antigen receptor T-cell (CAR-T) therapy, antibodies, bispecific T-cell engagers (BiTEs), and the importance of achieving measurable residual disease (MRD) negativity. To conclude, Dr Anderson addresses the possibility of achieving cure in myeloma by 2030. This interview took place at the 8th World Congress on Controversies in Multiple Myeloma (COMy) 2022, held in Paris, France.
Transcript (edited for clarity)
I’m very honored to be here at COMy and to be able to talk about the realistic possibility of cure in myeloma. I’m going to talk about some of the new technologies that we use now to monitor myeloma: mass spectroscopy; circulating tumor cells; circulating free DNA; and even single-cell sequencing not only of the tumor, but of the microenvironment. I’m also going to then talk about how we’re going to use some of the drugs we already know about for different uses...
I’m very honored to be here at COMy and to be able to talk about the realistic possibility of cure in myeloma. I’m going to talk about some of the new technologies that we use now to monitor myeloma: mass spectroscopy; circulating tumor cells; circulating free DNA; and even single-cell sequencing not only of the tumor, but of the microenvironment. I’m also going to then talk about how we’re going to use some of the drugs we already know about for different uses. Melphalan, for example, can induce mutations, which in turn can in fact be targets for immunotherapy. Bortezomib, the proteasome inhibitor, can induce an immune response in patients against their myeloma immunogenic cell death. The immunomodulatory drugs can actually trigger degradation of protein. A whole new class of protein-degrading compounds is coming to the clinic in myeloma and other cancers.
I’m going to move on to new targets. One of them is BRD9, which is a target in the myeloma cell. Another new target called EPRS, which turns out is in the microenvironment can overcome the high amounts of proline that are in myeloma patients. Finally, I’m going to talk about targeting the microenvironment. There’s a new target, CD73, which is expressed in myeloma and confers immunosuppression. I’m going to talk about how we’re trying to do precision medicine in myeloma. Targeting mutations, but it’s difficult because there’s so many mutations in myeloma, but adding in targeted therapies. An ERK inhibitor to restore sensitivity to IMiDs or a JAK inhibitor to restore sensitivity to CD38 antibodies. Then I’m going to talk about, obviously, the immune therapies and some new ideas about CAR-T cells first. Can’t we have a universal CAR-T cell? The idea would be you give an antibody that has a label on it, daratumumab, isatuximab, elotuzumab. It labels the myeloma and then give a universal CAR that only is activated and kills the cells that are already labeled with an antibody. That’s one example.
Then I’m going to talk finally about the bispecific T-cell engagers, which are really off the shelf and quite exciting because they bring the immune system to the tumor cell, exactly where you want it. Hopefully in so doing, increasing the potency and decreasing the side effects. Finally, having said all of that, how are we going to get to cure? Well, this meeting has highlighted that we can use four drugs: a proteasome inhibitor; an immunomodulatory drug; steroids; and a CD38 antibody. With or without a transplant, now we can get high levels of MRD negativity. Then as has also been highlighted at COMy this year, transplant would normally be done. But what’s being done now in clinical trials are immunotherapies, whether it’d be CAR-T cells and/or bispecific T-cell engagers as part of the first-line therapy in myeloma.
My prediction is that in 2030, we will cure myeloma. We will cure it by achieving MRD negativity and importantly, we will restore the immune response in patients against their own myeloma. Cure then will mean free of disease and off all medicines. It’s really the most exciting time ever for researchers, caregivers, and especially for patients.
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