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IMS 2026 | Potential of t(11;14) to identify and guide therapy for treatment-naïve GPRC5D-negative myeloma
Francesco Maura, MD, Memorial Sloan Kettering Cancer Center, New York, NY, discusses the potential clinical relevance of t(11;14) in treatment-naïve GPRC5D-negative myeloma, highlighting its potential as a biomarker for immunotherapy selection to avoid unnecessary toxicity and expense. Dr Maura notes that a subgroup of patients with GPRC5D-negative myeloma do not express GPRC5D and do not respond to certain therapies, and that a newly developed immunohistochemistry assay can identify these patients at low cost. This interview took place at the 23rd International Myeloma Society (IMS) Annual Meeting in Glasgow, UK.
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Transcript
I think this is a groundbreaking study because we don’t have a current biomarker for myeloma to select for therapies, particularly immunotherapies. We treat most of the patients more or less the same or empirically based on the doctor’s experience and preferences. So this is actually a biomarker that tells us something that was probably unexpected to most, that while BCMA is overexpressed in every myeloma cell, GCPR5D doesn’t follow the same path...
I think this is a groundbreaking study because we don’t have a current biomarker for myeloma to select for therapies, particularly immunotherapies. We treat most of the patients more or less the same or empirically based on the doctor’s experience and preferences. So this is actually a biomarker that tells us something that was probably unexpected to most, that while BCMA is overexpressed in every myeloma cell, GCPR5D doesn’t follow the same path. There is a subgroup of patients that are around 10% newly diagnosed and up to 20-40% relapsed, where GCPR5D is not expressed before getting any therapy. So people think GCPR5D is lost after the therapy, but in this case, it’s lost even before starting. And guess what? These patients don’t ever respond to any of these therapies. Because these therapies are expensive, are toxic, sometimes CAR-T are also very irreversible because, yes, it’s one shot, but it’s very expensive logistically and can cause toxicity. Knowing that this patient should not be treated with those therapies, I think it’s a benefit for everybody, in particular for the patient. The good news is that this assay and this observation were developed together with an immunohistochemistry antibody. That means that currently immunohistochemistry is how we diagnose myeloma, and adding an antibody is something cheap, reproducible, that anybody can do in every country in the world because it’s really like a few dollars. So it’s something that really can change our clinical practice without exceeding cost and actually one of the few things that might save costs these days.
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