Should Additional BCMA Therapy be Utilized After Previous BCMA Therapy?

At the 2024 Great Debates & Updates in Hematologic Malignancies meeting in New York, Andrew Yee, MD, Massachusetts General Hospital, Massachusetts, and Harvard Medical School, Massachusetts, discusses whether or not it is suitable for a patient to receive additional B-cell maturation antigen (BCMA) therapy after previous BCMA therapy.

Transcript:

Hi, my name is Andrew Yee, I'm the clinical director for the Center for Multiple Myeloma at Mass[achusetts] General Hospital, and I'm also an assistant professor of medicine at Harvard Medical School. I'm here today at the Great Debates & Updates [in] Hematological Malignancies [meeting] in New York. Today, I'm tasked with one of the debate topics, [which] is whether or not BCMA therapy is appropriate after prior BCMA therapy. And of course, my response is going to be: absolutely yes. 

Okay, maybe not absolutely always. But at least for the purposes of the debate, I'm going to try to make a vociferous argument in favor of why that's appropriate. It also reflects my practice as well. I think when we think about BCMA therapy, we have different modalities of therapy. We have antibody drug conjugates, though they're not currently approved, but it may be back on the market. We have bispecific antibodies, in which we have 2 bispecific antibodies. We have teclistamab and elranatamab, and we have 2 [chimeric antigen receptor] (CAR) T cell therapies. We have [idecabtagene vicleucel] (ide-cel) and [ciltacabtagene autoleucel] (cilta-cel), and one of the biggest developments at the meeting, well not exactly, was that we have 2 brand new approvals where ide-cel and cilta-cel are approved now in earlier lines of therapy. 

That's really going to change how we think about taking care of patients with multiple myeloma, and it's a really exciting time to be taking care of patients with multiple myeloma, and also for patients out there where these newer therapies are really going to be pivotal in terms of their care. 

Again, we're going back to the debate topic. I'm talking about using BCMA after BCMA, and there are several ways of thinking about this. There is a school of thought and care, in general, where [we ask], should you change classes of therapy? I think what my colleague is going to argue is that you should change class of therapy. But I don't think it's always that black and white.

In myeloma care, we can think of multiple examples where you don't have to change class. I can think of examples using pomalidomide after lenalidomide or using carfilzomib after bortezomib. So, you can use the same class and still achieve excellent results.

For the purposes of our debate, I was going to share a case of a patient I have who had a great response to ide-cel, but then developed a relapse of disease. I stayed in the same class, and I used teclistamab to treat his relapse, and this patient had an extraordinary response.

That's just an example from my own practice where you can use an anti-BCMA bispecific antibody after prior CAR T-cell therapy. There's clinical trial data that show responses that are compared to patients who are BCMA naive.

Then there's also some emerging real-world data that also bears that out. I think what gets complicated, though, when you look at real-world data, is that you might see maybe not as much response compared to a BCMA-naive patient, but I think it's kind of confounded because patients who've had prior BCMA therapy tend to be more heavily treated.

As a result, the responses may not be exactly the same as prior BCMA-naive patients. I think another point I was going to make in this debate is that once there's a little bit of an element of using BCMA after BCMA, I think in the future there might be a little bit more sophistication in terms of how we think about choice of therapy as we're starting to appreciate when patients relapse after prior BCMA therapy. Sometimes there can be biallelic loss of BCMA or there can be mutations in BCMA, but I think that's more in the future and [...] thinking about [the] how could be more sophisticated in terms of choice of therapy.

Source: 

Yee A. Debate- BCMA Therapy Followed by Another BCMA Therapy Is Appropriate – YES. Presented at the Great Debates and Updates in Hematologic Malignancies Meeting; April 5-6, 2024; New York, New York.