Updates in Frontline Therapies for Patients With Transplant-Ineligible Multiple Myeloma
At the 2025 Lymphoma, Leukemia & Myeloma (LL&M) Winter Symposium in Miami, Florida, C. Ola Landgren, MD, PhD, Sylvester Comprehensive Cancer Center, Miami, Florida, discusses recent updates in frontline therapies and advancements in patient outcomes for newly diagnosed, transplant-ineligible multiple myeloma (MM).
Transcript:
Hi, I am Ola Langren. I'm a professor of medicine and I'm Chief of the Myeloma Division and the Myeloma Research Institute at the University of Miami. I'm at the LL&M 2025 Winter Symposium here in beautiful Miami. This is the inaugural meeting for LL&M coming to Miami. We are very excited to have the meeting here.
I was asked to talk about transplant-ineligible newly diagnosed patients with multiple myeloma. That's a topic that includes a lot of new information. Thinking how the field has changed. It used to be a field where there was really nothing going on, to a field where everything is changing so fast. In 2024, there have been papers in the New England Journal of Medicine, in Nature Medicine, and other high-impact journals showing that this patient population can actually benefit greatly from a 4-drug combination using proteasome inhibition, immunomodulatory drug, low dose of steroid, and an immunotherapy with a CD38-targeted antibody.
It's very impressive to see that you have over 60% of these patients achieving MRD negativity after combination therapy. These trials also have continued treatment with what we refer to as maintenance therapy, using a low dose of an IMiD [immunomodulatory drug] with continued use of an immunotherapy with CD38-targeted antibody. You can continue to deepen the response over time, and this is because these drugs are very effective and also very well-tolerated. If you don't achieve MRD negativity right away, you may do it 1 or even 2 years later. These trials, if you look across the board and compare them to the transplant-eligible patients, you see the same pattern that you can achieve very high rates of MRD negativity.
For someone like me who's been in the field for many years, I think there's a striking change of pattern in the sense that you can actually have great deep responses independent of transplant eligibility status. A very important question to address for the field is, do we really need to talk about transplant-eligible and transplant-ineligible patients?
Because all the patients seem to benefit from these drugs. Also looking at what's going on beyond these trials that were just published, there are bispecific antibodies very much in development for early lines. How will they continue to deepen their responses? I foresee that we will have very powerful therapies that all the patients can actually tolerate, independent of age, and even some comorbidities can probably be okay. The role of transplant will have to be changed in the future, that would change the whole field for drug development. It's going to benefit patients.
Lastly, what I would like to emphasize here today, which is what I also talked about at the conference, is how this has really changed the face of the disease. The average age of onset for myeloma is about 70, about 50 and up. That's where most patients were diagnosed, less than 5% with myeloma diagnosed before the age of 50, but the midpoint is 70. If we put all the data in context of the average lifespan in the United States, the data would suggest that the lifespan for the general population is maybe 86 or something like those years. If you're diagnosed with myeloma around age 70 and you get great therapy, that could last for 5, 10 years. If there is a recurrence, we have new immunotherapies, you can get another 5, 10 years out of that.
Even with 2 lines of therapy, you actually can deliver a lifespan that's very similar to the general population. I have started telling my patients when they come in my clinic, if they have no high-risk features, no other comorbidities, I would typically say, ‘Unfortunately we don't yet have a cure for the disease, but we have very many very good therapies. I cannot 100% promise you, but there is a very high likelihood that you will have the same lifespan as a person with the same age and gender without the disease.’
That's a huge change from what it was when I was in fellowship, when the average survival was only 1, 2 or very rarely more than 3 years. We have come such a long way.
Source:
Landgren O. Updates in front line – transplant ineligible multiple myeloma. Presented at Lymphoma, Leukemia & Winter Symposium; February 7-9, 2025. Miami, FL.
