Should the Sequencing of BCMA-Directed Therapy be Used in Multiple Myeloma Treatment?

At the 2024 Great Debates and Updates (GDU) in Hematological Malignancies in New York, New York, Brea Lipe, MD, University of Rochester Medical Center, New York, New York, argues against the utilization of sequencing B-cell maturation antigen (BCMA)-directed therapies, noting the decrease of the treatment response among patients with multiple myeloma (MM) following this regimen.

Transcript:

Hi, I am Brea Lipe. I am a professor of medicine at the University of Rochester, where I'm the clinical director of the multiple myeloma program. I'm here today in New York City at the Great Debates [and Updates] in Hematolog[ic Malignancies meeting] and had the privilege of discussing BCMA-directed therapy and the sequencing of BCMA-directed therapy.

My presentation was on why we should not be planning to sequence our BCMA-directed therapies, because that's a terrible idea and [a] waste [of] good drugs. The take-home point of my discussion was that these BCMA-directed therapies that we have now, whether they're antibody drug conjugate, which we don't currently have, but are likely to have again in the future---we have bispecific antibodies and we have [chimeric antigen receptor] (CAR)T-cells. Bispecific antibodies and CART-cells, which we have now, are amongst the most effective drugs that we have in a heavily refractory patient population of patients with multiple myeloma.

These patients have seen [al]most everything there is in the space and they're still seeing high response rates. The durability of these therapies has been impressive [and] unprecedented compared to any other drugs that we've had in the past.

The point is, if we have these drugs that work so well, why on earth would we do anything to jeopardize that efficacy and durability? What we know is that when we sequence these drugs--- when we do 1 bispecific or CAR T-cell [therapy] after another---they still have reasonably decent response rates. But, the durability of those responses drops way down.

When we know that sequencing these therapies leads to inferior outcomes, we really should plan to avoid doing that. With the caveat being myeloma patients end up progressing and they run out of therapy and we're going to have to reuse drugs.

But, if that's the reality that we face, then we need to be more intelligent about how we sequence these drugs and we need to be smarter about how we use them and understand better the mechanisms of resistance. If we're going to sequence these drugs, we need to understand why they fail because it might be that we can recover activity if we intelligently design how we are planning to sequence these drugs or what drugs we use in the interval so that we can maintain some of the efficacy and the durability of these drugs.

Source:

Lipe B. Debate- BCMA Therapy Followed by Another BCMA Therapy Is Appropriate – NO. Presented at the 2024 Great Debates & Updates in Hematological Malignancies: April 5-6, 2024. New York City, NY.