The Path to Cure in Multiple Myeloma: How Emerging Therapies Are Changing the Landscape
At SOHO 2025, Sundar Jagannath, MBBS, joined Noopur Raje, MD, Krina Patel, MD, and other experts to discuss groundbreaking advances in CAR T-cell, bispecific, and trispecific therapies that are transforming multiple myeloma from a chronic disease into one that may now be considered curable.
Can you give an overview of your session at SOHO 2025?
Sundar Jagannath, MBBS: At SOHO 2025, the multiple myeloma session was quite exciting. We had Dr Noopur Raje giving us the latest development in CAR T-cell therapy, including—which was really remarkable—the early patient results that were reported of just injecting the vector into the patient. The patient's T-cells and circulation turned into CAR T-cells and the patients have all responded to treatment. It completely avoids all the manufacturing and time between.
Moreover, she went over some of the newer CAR T-cell therapies that are in the pipeline, with almost 100% response rates and deep responses—complete remission and minimal residual disease (MRD) negative. That set the tone that there a new set of treatment options available.
This was followed by Dr Krina Patel reviewing all the bispecific antibodies. They were also shown to be very effective, with an overall response rate of about 70% and even complete remission, MRD negative, in about 30% of patients. She also shared information about a trispecific antibody, which showed a response rate of almost 100%, and deep responses. The patient didn't even have to be admitted for step-up dosing. It was well tolerated. This, again, heralded a new development in the myeloma field. That was very exciting.
This was followed by Dr Paola Neri, who gave us an update on how to overcome drug resistance that develops with CAR T-cell therapy or bispecific antibodies. She discussed how, in the future, we should think about getting the best out of these kinds of treatment options. That was very interesting as well.
We had a couple of other presentations starting out with one on amyloidosis by Dr Suzanne Lentzsch, showing that amyloidosis has also become more treatable and curable with these newer agents, including bispecific antibodies. That was very exciting.
Dr Martha Lacey talked about the newer technology used to define MRD or MRD in the blood. With that preamble, I had a chance to talk about cure in multiple myeloma. What better place to share that with oncologists than SOHO 2025?
Defining cure is very important. Why? First of all, it is important for the patient to be told that they are not inflicted with an incurable, fatal cancer. Instead, we are going to tell them that multiple myeloma is now a curable disease. That brings hope, and that changes the whole dialogue of how the patient views the future.
The second thing is that, for the practicing oncologists who were in the audience, it was very important for them to know that myeloma is curable now. Therefore, their approach to patients can change because now they have a curable disease and they're going to help these patient cure. This will also make oncologists more willing to send the patient to clinical trials if a particular treatment paradigm is likely to be curative.
The pharmaceutical industry is also affected if we can come up with a definition for cure. If at the end of 5 years, we can say, "These patients are going to be cured," then they can design clinical trials with an endpoint of 5 years. They can enroll a newly diagnosed patient with myeloma, because right now the progression-free survival is 8 to 10 years, and overall survival has gone beyond 10 years in a transplant-eligible patient.
Nobody wants to fund a clinical trial. It is very expensive. Defining cure and having a definition that could be put in place at the 5-year mark helps the pharmaceutical industry to come forward with clinical trials in newly diagnosed patients with myeloma, with an aim towards curing myeloma. Not only that, when you design a curative treatment plan, pharmaceutical companies are willing to collaborate with their assets because they all want to be on the bandwagon for cure. That is important.
The third thing is whether the definition will also hold in relapsed and refractory myeloma. Now they can actually go forward with developing newer drugs—not after 4 to 6 lines of therapy. They can develop clinical trials for patients who failed 1 to 3 lines of therapy, and they can also go forward with a randomized clinical trial so that the drug development happens earlier and sooner. We need these drugs to be approved quickly so the patients can be cured. That is the advantage for the pharmaceutical industry.
Finally, for regulatory agencies, such as the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA), having a definition that would allow them to approve drugs earlier is also important. For all parties concerned, it is time to say that multiple myeloma is a curable disease.
The second step is, what is the definition? I gave a definition of cure. What is a cure? A cure in multiple myeloma is when the patient has no trace of cancer in their body. That is sustained over a period of 5 years without any treatment. Those patients can be called cured.
Now, how do we know the patient has no trace of cancer? We have to define complete remission. Complete remission means that there is no trace of cancer detectable in the blood or urine using the most sophisticated tests that are available, including the latest technology beyond immunofixation. That is important.
We also have to make sure there is no MRD in the bone marrow. That technology is now FDA approved, it’s called clonoSEQ. There is also functional imaging. We can do whole-body MRI or whole-body PET-CT scans so we can make sure there is no cancer anywhere in the body, head to toe.
With these tools, we can define whether a patient is in complete remission with no measurable disease in the bone marrow. For these patients, that is the definition of cure. If that is sustained for a minimum of 5 years, if they are not on any treatment, they could be declared cured.
The question is whether this definition should hold in relapsed myeloma as well. I gave the example from our center, where we have done retrospective research and published in Blood Advances, that this definition does hold. If you are able to sustain the MRD for 5 years and then stop treatment, these patients do not relapse for up to 10 years, fulfilling the criteria that they could be followed for 5 years without any treatment.
The reason for defining cure in myeloma is because of what was presented at the American Society of Clinical Oncology (ASCO) 2025 conference and the European Hematology Association 2025 congress and published in the Journal of Clinical Oncology. These are the long-term results of CARTITUDE-1, where the patient received a single infusion of a CAR T-cell therapy called cilta-cel between 2018 and 2019. When we followed these patients over a period of 5 years, with a median follow-up of 61 months, we noted that out of the 97 patients who participated in the clinical trial, 32 patients were alive and progression-free. That means that one-third of the patients were alive and progression-free.
Not only that, 12 of those patients studied at my center went through an annual evaluation with bone marrow for MRD detection by clonalSEQ in 11 of the 12 patients, and 1 patient had multiparametric flow cytometry. There was no measurable disease by MRD testing and also by PET-CT imaging. We documented for 5 years and these patients had no trace of cancer in the body. That proved that these patients were cured.
These patients had already failed all the currently available treatment, they had gone through 3 or more prior lines of therapy. They really did not have a good treatment option. It was between hospice or participating in the clinical trial. These patients went from hospice to cure. If we can do that in relapsed and refractory myeloma, I'm pretty sure we can do that in newly diagnosed myeloma in the earlier stages of the disease.
If the field begins to embrace the concept of “cure,” how should that change the way clinicians communicate with patients—both in terms of hope and in setting realistic expectations?
Dr Jagannath: That's a very good point. It's important that hope is conveyed. You can look at a patient and say, "Listen, so much rapid progress is coming. In your lifetime, we can say that you are likely to be cured. We would start you with quadruple therapy or whatever the frontline treatment is. Should your cancer come back 5 years later or 3 years later, all these immuno-oncology assets are there, including CAR T-cell therapy and bispecifics. They are likely to make your cancer disappear completely and not come back. We can cure you. We are hoping to cure you the very first time, but in case we don't accomplish that, we still have a shot at a cure should your cancer come back."
That sets the tone of dialogue between the patient and the physician, giving hope to the patient, but being realistic. Not everyone is going to be cured. In case the cancer comes back, they still have very good treatment options down the line. Amidst all of the assets that Dr Noopur Raje talked about, the new CAR T-cell therapy and the trispecific therapy category, one of them is going to hit the jackpot for each patient.
Overall, what do you feel is the most important take away from your session?
Dr Jagannath: The most important take away is there is extreme optimism in multiple myeloma. That optimism is based on all these clinical trials bringing so many different assets. Every year, 1 or 2 drugs are getting approved, and they are amazing drugs.
Our ability to detect minimal residual cancer or cancer in the blood or bone marrow, that technology is also improving. Our ability to look for cancer anywhere in the body with the functional imaging is improving as well. We are also understanding the biology better. What makes the cancer cells stick and how could we get rid of it? How does the cancer subvert the immune mechanism? How does it survive and become resistant? We are learning all that. With that, I'm pretty sure we should be able to get rid of the cancer once and for all.
