Key Takeaways from the Facebook Live Q&A: Dr. Sagar Lonial Answers Your Myeloma Questions
Dr. Sagar Lonial, a member of the IMF Scientific Advisory Board and the IMF International Myeloma Working Group, answers myeloma questions in a summary of the Facebook Live held on March 25, 2026.
Dr. Lonial opened this Facebook Live by highlighting a few topics in the field of myeloma:
The significant advances made in the context of newly diagnosed myeloma.
Dr. Lonial said, “We know now that for fit patients, and fit is truly in the eye of the beholder, but that for fit patients, the median expected first remission for a myeloma patient diagnosed today is somewhere between 10 and 15 years, depending upon genetics and other comorbidities that may be present at the time they are diagnosed.” Dr. Lonial explained that newly diagnosed multiple myeloma (NDMM) patients have experienced better outcomes “because of quadruplet-based induction using the anti-CD38 antibody daratumumab, in combination with high-dose therapy and transplant, as well as with maintenance therapy."
The movement of BCMA-directed therapies from late-line therapy to earlier lines of therapy
Dr. Lonial said, "I'm speaking specifically about CAR T cells as well as about BCMA-directed bispecifics, where the data presented in the last six months on early relapse is impressive and demonstrates that in early relapse — meaning first relapse — that some patients may do just as well and may even have longer remissions after that first relapse using BCMA-directed therapies. These treatments should give patients, caregivers, and families hope that we are not only going to make this potentially a chronic illness where patients live their lives with good quality of life and are healthy, but also perhaps increasing the fraction of patients that are cured.”
The meaning of cure in myeloma right now
Dr. Lonial said, “We had the first International Myeloma Society Cure Summit almost a month ago now, and the Tuesday after that clinic, I walked into a patient's room and had the privilege of telling them that based on that definition from a consensus group of myeloma physicians from around the world, that this patient met the definition of cured myeloma.”
Dr. Lonial continued, “So really exciting, especially when you consider that when I began my career in this field almost 25 years ago, the median expected survival was only two years, and now I'm giving you median first remissions of 10 to 15 years and even talking about the cure word. So, really exciting data that I hope will give patients a lot of important hope and make sure that you get your care in combination or conjunction with a major myeloma center so that you or your family member or your friend can get the benefits of some of these great new advances.”
After introducing the Facebook Live with these three points, Dr. Lonial responded to questions from attendees. (EDITOR’S NOTE: Viewers’ questions and Dr. Lonial’s responses have been edited for conciseness and clarity):
Is the New CAR T-cell Therapy—anito-cel—As Effective as Other CAR T-cell Therapies?
Dr. Lonial: We currently have two BCMA-directed CAR T-cells that are FDA-approved. The first one that was approved is ide-cel. The second one that was approved is cilta-cel. You’ve probably seen a wealth of data from trials, including CARTITUDE-4, which was looking at CAR T-cells in first relapse. What I think was so exciting about that trial was the long remissions, both for standard-risk and high-risk patients, and they didn't need any ongoing therapy. There was no maintenance therapy after the CAR T cells, so patients did well for a long time. The question from the audience here is about anito-cel, which is a new type of BCMA-directed CAR T-cell therapy. Just from a molecular perspective, it's a little simpler than what we've seen with either cilta-cel or ide-cel.
Early phase one and phase two data suggest that the rates of cytokine release or CRS, as well as ICANS or neurologic toxicity, or any other adverse events within the first six months, appears to be lower than historically what we've seen with either cilta-cel or ide-cel.
That's really encouraging in an early trial setting. Phase three trials for anito-cel are ongoing. We’ll see whether this improvement in adverse events translates into a larger group of patients and whether the benefit is better than the best available therapy.
I think it's certainly an exciting trial, and I think we'll see more or hear more about that in the coming year as we begin to follow it. One of the potential advantages of anito-cel is that it may have a different adverse event profile than the other BCMA-directed CAR T-cell therapies that are currently approved.
When Diagnosed with Myeloma, How Valuable Is It to Get a Second Opinion?
Dr. Lonial: Unless you're at one of the 12 or 15 major myeloma centers in the country, there always is a good reason to get a second opinion. I think that seeing a doctor who specializes in myeloma — that's all they see every day, all day when they're in clinic — is really important because there is a specialized expertise that comes from that experience.
However, it doesn't mean that you have to get all your treatment at that center. It may be hard to get your care at a specialized center, but I think you go to that specialized center with the intent of creating a plan, and identifying the best treatment approach. Then, you've always got access to that center down the road if you have questions, or if you have side effects or complications that your local doctor is not experienced with, because they don't have the same number of patients or the experience of treating solely myeloma patients.
You also potentially have the ability to go on trials and have access to new therapies sooner, and many of those are only available at specialized myeloma programs.
One of my colleagues in my cancer center says, ‘The only simple cancer is the one that you don't have.’
That’s a pretty straightforward answer to the idea of, ‘Well, my myeloma is pretty straightforward. My doctor tells me I don't need a second opinion.’
I don't know that that's necessarily the case. Seeing somebody who sees this stuff all the time can only add to your comfort, your state of mind, as well as provide resources for your local doctor who may gain benefits and knowledge from that second opinion as well.
If a Myeloma Patient’s Treatment Stops Working, What Next?
Dr. Lonial: There are a couple of different ways to frame that. With FDA-approved agents, we now have four or five different lines of therapy. If a treatment doesn't work, you certainly have the option of many other potential new treatments that are not even on a clinical trial.
Now, what a clinical trial does offer you is potential access to new drugs that may have different or fewer side effects. That is a big attraction of many of the new treatments that are in phase one, phase two, and phase three clinical trials; they may have different adverse event profiles, which may benefit you in your journey with multiple myeloma.
Yet, there are sometimes subtleties to the drug that is not working anymore, and there may be tricks that many of us who use these combinations know. We may look at the numbers and the imaging on a regular basis, and we may be able to make adjustments for your specific case. For instance, adding in other partner drugs.
As an example, if a bispecific isn't necessarily working or offering you the benefit, do you need to stop it or can you add in a medicine like pomalidomide? That might recapture the response. These are some of the subtleties that go into many of the treatment decisions that I think you benefit from when you're at a major myeloma center.
In short, there are several treatment approaches, both on and off clinical trials, and I think being aware of when to add them, when to subtract them, and when it's okay to just sit tight and watch those numbers. I think those are important considerations.
At First Relapse, How Long Must Kyprolis (carfilzomib), Pomalyst (pomalidomide), and dexamethasone (KPd), Be Administered?
Dr. Lonial: That is a situational answer in terms of how long it's working, what the magnitude of response is, and what kind of situations patients are in. I often think of a treatment like KPd as a bridge to get to something else, whether it's a bispecific or a CAR T. Are these treatments definitive therapy or bridging therapies? I think there are several questions that can come into play to answering that specific question. Also, I need more details and perhaps a conversation outside of this forum to be able to really answer that.
If Myeloma Is Located in the Sacrum and Is Causing Hip Pain, Would a Hip Replacement Be a Treatment Option?
Dr. Lonial: I think the real question is that the sacrum is obviously physically separate from the hip joint for the most part. The question is, are there areas there that could benefit from additional therapy, either injection, like a kyphoplasty or a vertebroplasty? I have had patients where we've done that [injection/kyphoplasty/vertebroplasty] in the sacrum to suppress some of the nerves that may be causing pain.
Yet, this is a situation where seeing a pain specialist or an interventional radiologist may offer you some benefit. A hip replacement would only be indicated if you were worried that there was significant damage to the joint that was causing the pain as opposed to potentially myeloma-related pain. Even if it's in the joint, which might be remedied with therapy if your disease is beginning to grow again. There are several ways to answer that question, but getting imaging, particularly an MRI dedicated to the sacrum and hips, followed by potentially a consultation with an interventional radiologist, might offer you some benefit.
Are There Trials Other Than the MajesTEC-3 Trial, in Which Patients Have Been Pre-treated with Daratumumab and Teclistamab?
Dr. Lonial: There are two ways to answer that question. First, MajesTEC-3 was a randomized trial of teclistamab plus daratumuamb, or TEC-DARA, versus the best available therapy. The trial asked is the doublet of TEC-DARA better than other available therapies? In that trial, most patients had not been exposed to DARA previously.
Most trials currently or most exposures for dara are really in the induction therapy setting. It’s four cycles of dara. You then go on to transplant and then likely are on lenalidomide-based maintenance afterwards.
We’ve not seen a lot of dara after that. In that context, I wouldn't have any concerns or worries that the dara would not be offering significant benefit if a patient were to get TEC-DARA.
We’re also all very excited to potentially see in the future, the data from MajesTEC-9, which looks at single-agent teclistamab in the context of dara-exposed or dara-resistant patients. Once we have this data, we'll understand the relative additive benefit of dara, whether you're dara-naive or your DARA-exposed or even dara-resistance. We're likely going to see a little bit more on that in the coming months.
Will Newly Diagnosed Multiple Myeloma (NDMM) Patients Be Able to Begin CAR T-cell Therapy as Their First Line of Treatment?
Dr. Lonial: We need a bigger trial, and the CARTITUDE-6 is that bigger trial to understand whether in a population of patients that the CAR T-cell therapy is easier than the transplant. I think we will know more about this in probably the next few years, but certainly a majority of patients do very well with CAR T-cell therapy in terms of side effects in the first six months. Yet, some patients do have side effects and complications. Weighing that on balance with a transplant is really an important question. Also, we have such a long track record with transplant. For example, we see 10 to 15-year remissions with a quad-induction transplant and then risk-adapted maintenance after that.
Are Clinical Trials Only for Patients Who Run Out of Treatment Options?
Dr. Lonial: The answer to that question is easy. No, they are not. We, at our center, have clinical trials for patients at every phase of their disease. We have patients with smoldering; we have newly diagnosed trials; we have early relapse; we have late relapse; we have five prior lines of therapy; and we have exposed and resistant to every available therapy out there.
Until we have one simple treatment that is good for everybody and cures everybody, there will always be a role for clinical trials. And even when we have those, as they had with the blood cancer Hodgkin’s lymphoma. In this cancer, they continued to work on refining those treatments with trials to see if they could reduce short-term and long-term side effects or toxicities.
From my perspective, every patient in every phase of the disease is potentially a clinical trial candidate, and that's the benefit of being at a major myeloma center, so that you can get those kinds of benefits as a potential option if you need it.
What Is the Definition of Cure in Multiple Myeloma?
The cure definition is five years of continuous MRD negativity at 10-6 six with a negative PET-CT scan, and not on therapy. One of the real shifts in the way that we're thinking about myeloma therapy in 2026 and moving forward is that while myeloma historically has been dependent on continuous therapy; we're getting away from that model. We’re trying to get curative regimens, get sustained MRD negativity, and potentially discontinue treatment. That's not something we could do with our previous classes of drugs, as good as they were.
These are things that we can begin to think about now with agents like bispecific antibodies, CAR T-cell Therapies, the CELMoDS like iberdomide and mezigdomide. Many of these new classes of drugs potentially can get us to the point of discontinuation of therapy and get us to an ultimate cure.
How Is Venetoclax Being Used in Myeloma?
Dr. Lonial: We know that myeloma patients with translocation 11;14 are sometimes slower to respond to induction, but they actually gain significant benefit from high-dose therapy and autologous stem cell transplant (ASCT), almost more so than many other subsets of myeloma. At the same time, we, on average, gain significant benefit from the Venetoclax, which targets BCL2 overexpression. This overexpression is one of the major issues in patients with t(11;14).
Today, regarding Venetoclax, the question is, what are better partners with this drug? We hope to see some new data about potential Venetoclax combinations in the coming months.
How Effective is a Second Round of CAR T-cell Therapy After Relapse?
Dr. Lonial: It depends on the target, and it depends on the CAR T-cell therapy itself. If the target is different, there clearly is a track record for significant and deep responses for many patients. For instance, if you got BCMA-directed CAR T-cell therapy, and you relapsed. Then, you got a GPRC5D-directed CAR T-cell therapy; the latter could offer significant benefit. “If you've had a BCMA-directed CAR T-cell therapy, then going back to another BCMA CAR, you may want to understand the mechanism of resistance. This is something that we don't fully appreciate. There are differences in patients who relapse at six months after CAR T-cell therapy versus somebody who relapses three years after CAR T-cell therapy.
One of the questions that many of us in the field are asking is, ‘Is that BCMA receptor still normal or is it mutated?’ Several of us, particularly at major myeloma centers, now have sequencing tests we can use to evaluate BCMA to understand whether that BCMA is normal or mutated.
If it's normal and there was a long first remission, one could consider a second BCMA-directed CAR T-cell therapy. I've done that for a few patients and have seen significant benefits as well. It's a complicated question, lots of data in terms of how to interpret this, but certainly at the right places, there may be a role for re-treating with the same target with a different CAR T-cell therapy.
Do Myeloma Patients Need Maintenance After MRD Negativity?
Dr. Lonial: This is a really hot topic in our field right now, particularly as you heard me talk about limited-duration maintenance therapy. We’re starting to appreciate that patients who are MRD negative at year two and year three after a transplant may be able to discontinue. That to me means that your MRD-negative at 10-6, so less than one in one million cells with myeloma. Also, MRD-negativity has been sustained for at least a year, at two separate time points, two and three years out. Patients with these factors are the group we're beginning to have these conversations with.
Yet, you may not have MRD testing available. For example, many of my patients I've been taking care of for 15 to 20 years, we don't have MRD status on many of them. For that reason, they're choosing to continue on lenalidomide maintenance because we just don't know. That’s a reasonable approach as well, but I think these are some of the questions that we're beginning to answer.
There's some data from the UK; there's some data from our center [Winship Cancer Institute, Emory University] and other emerging centers that suggest that two years of sustained MRD-negativity may be sufficient to be able to talk about discontinuation of maintenance therapy. There are a number of factors that play into that, so it's not a simple yes or no question.
I Have Myeloma with a 17p Deletion, But I’m MRD-negative, 10 Years Post-Transplant. Is It Okay for Me to Get Off Revlimid (lenalidomide) Maintenance?
Dr. Lonial: Again, it's a hard question for me to answer because I don't know all the specifics of your case. Yet, certainly, I've had patients exactly like what you described, who told me they were coming off their Revlimid maintenance and are now five years out in ongoing MRD negative remission. I think it's certainly a discussion worth having with your physician or myeloma specialist regarding whether you can discontinue maintenance at this juncture, given how long you've been in remission.
Should I Wait to Start Treatment to Request a Second Opinion?
Dr. Lonial: I think that that really in part depends on how urgent the need for treatment is. I never want to tell you to wait and delay treatment and potentially cause your body harm by waiting. Yet, at the same time, if you're able to wait, I think it's a good idea because I think that a second opinion may give you reassurance that you're going in the right direction. Or it might look at the picture slightly different and perhaps tell you to go in a slightly different direction. It really depends on a number of factors as to whether or not you should wait.
What Are Your Thoughts on the REVIVE Trial to Prevent Disease Progression?
Dr. Lonial: There are a number of trials evaluating patients with high-risk smoldering myeloma (HR-SMM). We even have an FDA approval now to prevent the progression of HR-SMM in the context of daratumumab. There are a number of randomized phase three trials being done in the U.S. I would encourage participation in those trials, if you meet the definition of HR-SMM. If you're outside of the HR-SMM group, I think a discussion with a myeloma specialist about whether that trial is optimal for you does potentially make sense.
Stem Cell Harvest and Storage: What Are the Side Effects?
Dr. Lonial: The side effects from mobilization are pretty minimal. You may get a little bit of GI disturbance from the Mozobil® (plerixafor), one of the medicines used to improve or enhance stem cell collection. You may get some bone pain from the G-CSF, but otherwise, stem cell mobilization is relatively straightforward.
Are There Any Tests That Can Predict Treatment Efficacy and Guide Myeloma Therapy Choices?
Dr. Lonial: We don't have that ability to use sort of ex-vivo testing to do that, except perhaps with venetoclax. Again, this is where somebody with a lot of experience in taking care of myeloma patients can guide you through this process. While we don't have a hundred percent predictor of a response in the context of relapsed myeloma, we certainly do have experience and access to clinical trial data, and an expert may be able to help you make those decisions.
If I Have High-Risk Smoldering Multiple Myeloma (HR-SMM) Without CRAB Criteria: Should I Start Daratumumab?
Dr. Lonial: Darzalex® (daratumumab) is FDA-approved for the management of patients with HR-SMM. There also is a randomized phase three trial evaluating daratumumab plus Revlimid® (lenalidomide) and dexamethasone, versus lenalidomide and dexamethasone. It's an important trial. We’ve got 50 patients left before we complete enrollment, and this trial will ask the question, ‘Is more daratumumab better or worse for HR-SMM?’ I'd encourage you all, if you're able to go on that trial, please take a moment to potentially consider it.
In case you missed it, you can still watch a replay of the Facebook Live Q&A in its entirety.