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IMS 2024 | An insight into the sequencing of CAR-T and bispecifics in myeloma
Rafael Fonseca, MD, Mayo Clinic, Phoenix, AZ, provides valuable insight into the sequencing of CAR T-cell therapy and bispecific antibodies in the treatment of multiple myeloma (MM). Dr Fonseca highlights that, from currently available data, it is likely better to utilize CAR-T first and then consider a bispecific when relapse occurs. This interview took place at the 21st International Myeloma Society (IMS) Annual Meeting, held in Rio de Janeiro, Brazil.
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Transcript
One of the most common questions we would get right now is, you know, how do I deal and select with BCMA-targeting agents? They have come in multiple flavors. Right now, we don’t have the ADC, which is belantamab, but it’s likely to come back into the market. But we have CAR-Ts. We have two of them that are commercially available and others that are being developed to target BCMA. And then we have two commercially approved bispecifics and then more still in development...
One of the most common questions we would get right now is, you know, how do I deal and select with BCMA-targeting agents? They have come in multiple flavors. Right now, we don’t have the ADC, which is belantamab, but it’s likely to come back into the market. But we have CAR-Ts. We have two of them that are commercially available and others that are being developed to target BCMA. And then we have two commercially approved bispecifics and then more still in development. Now fortunately there’s other targets that are available for the treatment of myeloma. We have GPRC5D and we have FcRH5 and those are moving quite along well in their development. In fact we have one commercial product which is talquetamab. The questions about sequencing really are focused on two things: one is do you switch the modality, that is you go from CAR-T to bispecific and vice versa. The second is should you switch targets? The majority of people right now think that it might be better, and the way we can do it, regulatory perspective, is to go first with a CAR-T and then move later to a bispecific. Obviously, we need more data to be a little bit more definitive about that statement. There’s something very interesting. If you give a patient a CAR-T product, and let’s say they have one year, two years, three years, or more of disease control, all of that time, the CAR-Ts are fighting against the myeloma cells, but the person’s own T-cells are still happy and healthy. So were that patient exposed to a bispecific, that bispecific is going to find a very good ground where those T-cells can prove themselves. If you were to do a bispecific and then decide to move to a different target bispecific, you could get responses but there’s also a significant risk that those T-cells are now what we have described scientifically but colloquially is understood they’re ‘exhausted’. So maybe it’s not the best scenario, and also having seen CAR-Ts after bispecifics, the responses are a little bit lower, so as of now we prefer CAR-T followed by bispecific but of course we’ll need to see more data in that regard.
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