ASCO 2024 | Sequencing immunotherapies in multiple myeloma

There are a number of approvals for multiple myeloma with new CAR-Ts and bispecific antibodies. Indeed, there have been recent approvals for moving these in first and second relapse for CAR-Ts, and this is now creating a scenario where it’s becoming increasingly important to understand how we sequence these therapies one after another. And the talk is to essentially explain to community and academic oncologists alike how we sequence these at our institution and on the basis of data that we’ve produced and the literature that’s there, the best way to do this. This is an evolving field that is going to be increasingly important in the future. And the biology behind the resistance mechanisms to CAR-Ts and bispecific therapies is being revealed as we speak. This has to be incorporated into how we sequence these therapies. So my talk is based on that.

What we are finding in a nutshell is that CAR-T patients, when they relapse, are generally relapsing after a period of a year to three years, and they’ve been off treatment for a while. So there is a potential for retreating them with different things. The best at the moment seems to be giving them a bispecific antibody salvage, and other options seem to be autologous transplants that can reset even the low blood counts that these patients have sometimes. A second CAR-T is also possible, it can’t be given immediately when they relapse, but sometimes a longer duration after they relapse or changing the CAR-T construct does help. I’m going to explain some of the biology behind why that’s important. In the case of bispecific antibodies, we have options in terms of different targets. So switching the target seems to work. That’s an important consideration because the bispecific patients are treated continuously and they develop resistance because they lose the antigen sometimes or they undergo mutations in the antigen. They can also be treated with CAR-Ts or autologous transplant. And another consideration with bispecifics is that combinations with a second bispecific or other older myeloma drugs, like antibodies or pomalidomide, are also going to result in impressive outcomes for these patients. In summary, there’s a lot of optimism even when patients fail these new treatments because you can sequence them and do it in a rational way biologically.