Treatment Options for When Immune Therapies Fail Among Patients With R/R MM

At the 2024 Lymphoma, Leukemia & Myeloma (LL&M) Congress in New York, New York, Joseph Mikhael, MD, MEd, FRCPC, Translational Genomics Research Institute, Phoenix, Arizona, discusses treatment possibilities for patients with relapsed/refractory (R/R) multiple myeloma (MM) when immune therapies, such as antibody drug conjugates, CAR T-cell therapy, and bispecific antibodies, fail.

“There's still a lot to learn about this topic. We've come a long way, and I really do think we can give greater options to our patients even when they fail immune therapies,” concluded Dr Mikhael.

Transcript:

Hello, my name is Dr. Joseph Mikhael. I'm a professor at the Translational Genomics Research Institute and the chief medical officer of the International Myeloma Foundation. It's absolutely my pleasure to be here at the LL&M Conference and be a part of the relapsed myeloma session.

So much has changed in myeloma over the last several years, and I've been asked to address the issue of what happens when immune therapies fail so quickly. Those immune therapies are the ones we think of as antibody drug conjugates, CAR T-cell therapy, and bispecific antibodies. These have really become the mainstay of late relapse and becoming the mainstay of early relapse multiple myeloma. The challenge is what happens when a patient fails or relapses after one of those? This is an area obviously where we don't have a ton of data yet and we're generating this information from multiple databases, but I want to approach it in a couple of ways.

Firstly, why does this happen? What is the nature of that resistance? Often, it's B-cell maturation antigen (BCMA) resistance and is it because we lose the BCMA or are there other essential features of those therapies that lead to the resistance of the target, or by some means exhaustion of the immune system for these immune therapies?  Secondly, more practically, what do we do about it? And no one really knows the answer. I'm always given the topics where no one really knows the answer, but we try to use the evidence in the best way that we can.

A couple of leaving principles were the following: [First], if both are both available, CAR-T and bispecifics, it's likely better to go CAR-T first and then bispecific in that those T-cell get a rest between the grade infusion of T-cells at a CAR-T and the engagement later in bispecifics. Number 2, is that BCMA is a resistant target, meaning that we can go often from 1 BCMA to a different BCMA therapy, be it CAR-T or bispecific or even antibody drug conjugate. There may be a reduction in the efficacy to some degree, but it is still a valid approach.

And lastly, think outside of BCMA. Now we're generating therapies with a G protein-coupled receptor, class C, group 5, member D (GPRC5D) target, even the Fc receptor-homolog 5 (FcRH5)

target, and sometimes often going back to prior therapies or therapies that have not been used. Obviously with newer, smaller molecules like CELMods, selinexor and others, we do have options to maximize our ability to use immune therapies.

There's still a lot to learn about this topic. We've come a long way, and I really do think we can give greater options to our patients, even when they fail immune therapies.

Source:

Mikhael J. The Relapsed Refractory Patient: When Immune Approaches are Ineffective. Presented at Lymphoma, Leukemia & Myeloma Congress; October 16-19, 2024. New York, NY.