Emerging Therapeutic Options for Patients With Relapsed/Refractory Multiple Myeloma
At the 2026 LL&M Winter Symposium in Amelia Island, Florida, Sikander Ailawadhi, MD, Mayo Clinic, Jacksonville, Florida, discusses the rapidly evolving multiple myeloma treatment landscape.
Dr Ailawadhi explores how advances in CAR T-cell constructs, bispecific antibodies, and CELMoDs are expanding treatment options across disease settings while emphasizing the importance of individualized, patient-centered decision-making.
Transcript:
I'm Sikandar Ailawadhi, I'm a hematologist oncologist from Mayo Clinic in Jacksonville, Florida, and I lead our myeloma group at Mayo Clinic. It is important to think about the new molecules that have just come under discussion at the LL&M Winter Symposium.
There are several new classes of drugs that are coming up in multiple myeloma and newer agents that are being discussed within previously available classes. I think the ones most important or boiled to the top of my mind are some newer CAR T-cell therapy, which was just discussed in a session. Looking at not just the use of previously available CAR-Ts in earlier lines, in novel settings like consolidation, or patients who have leftover disease after transplant, or even in place of transplant as a de novo standalone consolidation approach. A lot of these situations were discussed in the setting of cilta-cel, which is a currently available CAR-T, but then we also discussed within the CAR-T realm about the dual targeting CAR-Ts against CD19 and BCMA. This CAR-T, which is called Gracell (GC012F), was discussed about where is the benefit, what are the data, which is excellent and very encouraging because not only the CAR-T showed deep responses as we have expected now from CAR T-cell therapy, but also importantly, it did not show the dreaded side effect profile, the neurotoxicity etc because it seems that this design of the compound does not really cross over the blood-brain barrier to cause all those CNS effects. The currently available CAR-Ts in different novel uses and then novel CAR-Ts that may be coming down the pipe quite fast–hat was the CAR-T realm that we talked about.
Other than that, we also talked about different uses of bispecifics. Within the bispecific realm, thinking about these have provided excellent deep responses. Some of the data that was just presented at ASH of 2025, where as early as second-line of treatment, bispecific teclistamab and dartumumab combination is giving excellent, deep, durable responses. In fact, in some projections, it is talking about a 15 to 17 year median PFS. That is phenomenal, unprecedented, never heard of. In addition to the currently available bispecifics being used in such good manner, we also talked about some different uses of the bispecifics, some out of the box thoughts. For example, a study from University of Miami showing that patients who got their induction therapy and then got a fixed duration of 4 to 6 cycles of bispecific lenvoseltamab based on MRD testing that reached 100% percent MRD negativity at the end of those 6 cycles. This is, amazing because it brings up the thought, should we really be doing a transplant, could we give up that need for a transplant– that's a very important question and thinking about it, since our bispecifics and even CAR-T can be used in many more patients, irrespective of age and "eligibility" of transplant, could that be a uniform approach that we could use for everybody?
We also talked about the bispecific use in frontline therapy, meaning do we really need that quad therapy that we've been talking about, or could we just get rid of those agents and directly go to a bispecific? That was the discussion about CAR-T and bispecifics.
Then we also touched upon some newer agent classes, for example, CELMoDs. These are an improvement on the preexisting IMiDs and what is their current clinical trial makeup, where are they being brought up – early relapse, late relapse. But again, important to keep in mind, these are a completely oral class of drugs. That brings up that patient-centric approach where we need to pick up the criteria that are suitable for our patients. We can talk about CAR-T bispecific, they're amazing, but what if a patient is not able to get to those classes of drugs– that's where these newer compounds like CELMoDs come, which can be combined very easily with our existing drugs. In some cases, even we discussed using these after prior bispecific or CAR-T use and how amazing the responses are there.
It is very important for a clinician to think about the different factors are to consider when making a decision about a treatment for a given patient. In fact, I would say it's not just for a newly diagnosed setting, or for a transplant setting, or a CAR-T setting. It should be a thought process in our mind every time for every patient, whenever we are making decisions for switching a treatment or starting a new treatment. The way I think about it is 3 different categories, which we also discussed in one of the presentations at the meeting, talking about patient-related factors, disease-related factors, and treatment-related factors. Then listing all of those in mind and deciding who would benefit most from which treatment, because it's not just about getting a response, but sustaining that response, which can only come when the patients stay on the treatment and tolerate it better.
We talked about, for example, the broad 4 categories of side effects that come from CAR-T and T-cell engagers, namely CRS or cytokine release syndrome, ICANS or the neurotoxicity, which could be early or in another category, delayed neurotoxicity. Then we also talked about infections, which need to be handled very aggressively and prevented very nicely in these agents, and then low blood counts or cytopenias, hese are important considerations, the CRS, neurotoxicity early or delayed, infections, and cytopenias when we are deciding how to handle a T-cell engager or a CAR-T in a patient.
Then we also talked quite a bit about the other toxicities which are very important for the patient's quality of life. For example, IMiDs or lenalidomide/pomalidomide that are causing muscle cramps, joint aches, diarrhea, fatigue, etc. We noted that CELMoDs can be given without a lot of these side effects and It's important for a clinician to be thinking about these treatment-related factors, disease-related factors, and patient-related factors, especially their comorbidities, other medications, interactions, and then take a decision about what the patient's next treatment should be.
When we think about what do learners most need to know right now with all of this data and this amazing information coming, I think the important piece is to be abreast with knowledge, and that's why it's important for these excellent symposia and conferences, which bring in the contemporary topics so that we can all educate ourselves and stay abreast with all the knowledge. But then also realizing that we now have the right tools available at our disposal, that myeloma, where we are talking about this functional cure, can hopefully get to the point of cure in the very near future. We need to keep figuring out how to use these tools to the best of their ability so that we can get the maximum benefit to the patient.
It is becoming a very busy landscape with a lot of different options. It's important for all the learners, for everybody who's consuming this data to realize that we have these tools, but we're still trying to figure out how best to use all of them. Partnering between the academic centers and the community centers becomes even more important now so that we can make the right decisions for the patients at the right time.
Source:
Ailawadhi S. New molecules in refractory myeloma (CelMoDs & iMIDS) - Updates from 2025. Presented at LL&M Winter Symposium; January 30-February 1, 2026. Amelia Island, Florida.
