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Real World FAQs in Multiple Myeloma
Expert Perspectives on Real-world Decision-making in Multiple Myeloma: Answers to Frequently Asked Questions

Released: December 26, 2025

Carol Ann Huff
Carol Ann Huff, MD
Thomas G. Martin
Thomas G. Martin, MD
Adriana Rossi
Adriana Rossi, MD
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Key Takeaways
  • With bispecific antibodies, CRS onset generally occurs within 24 hours if administered intravenously and 48 hours if administered subcutaneously.
  • Experts recommend referral for CAR T-cell therapy evaluation at the time of relapse after first-line therapy.
  • Choice of maintenance therapy following initial therapy with daratumumab, lenalidomide, or the combination should involve shared decision-making with patients and their caregivers.

In this commentary, Carol Ann Huff, MD; Thomas G. Martin, MD, and Adriana Rossi, MD, address questions posed by the audience during the recent symposium titled, “Steady Progress in Multiple Myeloma: Applying New Data and Updated Guidelines Throughout Treatment” held during the 2025 American Society of Hematology annual meeting.

How do bispecific antibodies and other therapies, such as CAR T-cells, compare and contrast with one another? 

Thomas G. Martin, MD:
This is a great question, and there are significant differences, particularly in how these immunotherapeutics are administered, the expected toxicity, and how the individual patient is evaluated and monitored. Patients referred for CAR T-cell therapy must be evaluated by a specialist at a CAR T-cell center, be reasonably fit to undergo the treatment, and have significant social/caregiver support. Bispecific antibodies, on the other hand, are off-the-shelf therapeutics, can be given by subcutaneous injection (elranatamab, talquetamab, teclistamab) and are associated with less severe cytokine-release syndrome (CRS), which typically occurs within the first 48 hours of subcutaneous injection (or within 24 hours of intravenous dosing). There are also differences among the 4 approved bispecifics regarding the required schedule and monitoring during step-up dosing, leading some centers to favor certain bispecifics based on administration and whether the bispecifics can be more easily transitioned to outpatient dosing. All the bispecifics provide potent anti–multiple myeloma (MM) effects with deep and durable responses reported for patients with late-line relapsed/refractory (R/R) MM. Overall, healthcare professionals should become comfortable/familiar with multiple bispecific antibody agents, including at least 1 BCMA-targeted therapy and at least 1 GPRC5D-targeted therapy, allowing experience to help guide therapeutic choice. These drugs will likely gain approval in earlier lines of therapy and will be incorporated into many different multidrug combinations. In the future, these agents will be used throughout the MM treatment paradigm and every patient, fit or frail, will likely receive these agents as part of their MM treatment.

Carol Ann Huff, MD:
I strongly agree that HCPs should become comfortable using at least 1 BCMA-targeted and 1 GPRC5D-targeted bispecific antibody. There is limited value in having access to every agent initially; the priority is gaining experience with management, monitoring, and toxicity oversight. These are highly effective therapies.

When and how should dosing frequency of bispecific antibodies be adjusted in patients with sustained responses?

Thomas G. Martin, MD:
This is a very important question, and changes to administration frequency does depend on the depth of response. Approximately one third of R/R MM patients do not respond to single-agent bispecific therapy, approximately one third progress relatively early, often between 3 and 9 months, and then there is a group of patients who do extremely well and can remain in remission for 12 months or more. For me, if a patient’s light chains are undetectable after cycle 3, I am very comfortable moving to less frequent dosing of the bispecific antibody. Because of the kinetics and half-life of the M-protein, the M-protein may persist for many months, but if the light chains are undetectable, that suggests most plasma cells have been eliminated, and I am comfortable reducing the dosing frequency at that point.

Carol Ann Huff, MD:
What dosing schedule do you move it down to?

Thomas G. Martin, MD:
I approach the dosing schedule in a stepwise fashion. For example, with teclistamab, I typically follow a pattern similar to daratumumab, with weekly dosing for approximately 8-12 doses, then moving to every other week for another 6-12 doses, and eventually transitioning to monthly dosing. I will say that I currently have several patients in their 80s who are in remission for >1 year and are receiving dosing every 10 weeks, and in some cases even every 12 weeks. Obviously, this approach is off label, but it has been very convenient for patients and offers a very good quality of life.

Carol Ann Huff, MD:
We have done the same for patients who are doing well, tolerating therapy, remaining in remission, and not needing to come in as frequently. Although this approach is off label, not having to re-escalate dosing appears to be feasible, and patients continue to do well from a CRS perspective as well.

Adriana Rossi, MD:
I also think this may lead to better durability of response, because we are not driving the T-cells continuously, maybe causing less T-cell exhaustion, so I absolutely agree.

What are your thoughts on sequencing and selecting a CAR T-cell therapy for today’s patients with R/R MM?

Adriana Rossi, MD:
I should start with the disclaimer that I am a strong believer in CAR T-cell therapy, and I think we are largely limited by access. In terms of ideal sequencing, I think that CAR T-cell therapy should be the first therapeutic option for BCMA-directed therapy in 2025 and 2026, but the reality is that not all patients are able to access it. If a patient is able to proceed to CAR T-cell therapy, I think that should be the preferred option, largely because of the quality of life and the “single-treatment” nature of the CAR T-cell treatments. In the United States, we currently have 2 approved BCMA-directed CAR T-cell products, and we now have robust real-world datasets as their use has expanded. This gives us flexibility to better tailor therapy to individual patients. Among these, ciltacabtagene autoleucel (cilta-cel) appears to be more potent in terms of efficacy, but this also appears to be associated with higher toxicity. By contrast, idecabtagene vicleucel seems to have lower efficacy but also a more favorable toxicity profile. Together, these options allow us to select the most appropriate CAR therapy for different patient populations at a given time. 

Thomas G. Martin, MD:
I think it is important to discuss the timing of CAR T-cell therapy as cilta-cel is now approved in the second-line setting and idecabtagene vicleucel in the third line. So I will ask my colleagues, for a patient who relapses on lenalidomide maintenance and thus is lenalidomide refractory, is this the right time to recommend CAR T-cell therapy? If yes, then we want to send a clear message to our community providers that we want to evaluate patients for CAR T-cell therapy right when they become lenalidomide refractory.

Adriana Rossi, MD:
I think part of the challenge, and what makes this topic so complex is that many factors need to be considered. For example, in a 35-year-old patient who is progressing within 1 or 2 years and is a functionally high-risk patient, I think that CAR T-cell therapy would be appropriate. By contrast, for someone who has been receiving lenalidomide maintenance for 8 years and is experiencing only biochemical progression, perhaps not. So again, having this option available allows me to use it for the right patient at the right time.

Thomas G. Martin, MD:
I think there is quite a bit of controversy in this area as well, particularly when we talk about functional high risk. You mentioned functional high risk with your younger patient. What exactly defines functional high risk after a quadruplet regimen? In patients considered to have functional high-risk disease, many would favor treatment with  CAR T-cell therapy, what I consider the current best available therapy. Again, it comes back to the right patient, the right therapy, at the right time. However, in the phase III CARTITUDE-4 study, if we look specifically at the standard-risk subgroups—remember these are patients with lenalidomide-refractory MM after receiving 1-3 prior lines of therapy—the 30-month progression-free survival is more than 70% in patients receiving cilta-cel, almost doubling the progression-free survival compared with the standard-of-care therapies. So CAR T-cell therapy in both the functional high-risk and standard-risk lenalidomide-refractory population has shown benefit.

Carol Ann Huff, MD:
I completely echo everything you have said. The only additional point I would make is that even in the older transplant data, patients with stage I or favorable-risk disease actually appeared to derive the greatest benefit from transplant. In a similar way, at this point, I am probably using cilta-cel in the second-line setting primarily for patients with functional high-risk disease. That said, I would like to see longer-term follow-up to be confident that these benefits are durable in those patients. As we develop CAR T-cell therapies with fewer potential adverse effects, these discussions will become easier. I would also argue that CAR T-cell therapy can be cost-effective, despite the high upfront cost. If patients remain disease free, the overall benefits in terms of quality of life and cumulative healthcare costs may justify that investment.

When should HCPs be referring patients for potential CAR T-cell therapy, especially now that quadruplet regimens are being used earlier in the treatment course?

Carol Ann Huff, MD:
I would say referral should occur at the time of relapse after first-line therapy, so that patients can be evaluated and the appropriate discussions can take place. It is very difficult, in my mind, to precisely define every aspect of functional high-risk disease, but we are always happy to see these patients and engage them in those conversations.

Adriana Rossi, MD:
Exactly, and to your earlier point, if it works well in high-risk disease, it may work as well, or even better, in standard-risk disease. I think it is very important that for anyone who might be a candidate for CAR T-cell therapy to have that conversation at the time of first relapse, even if the decision is that it is not the right time. That way, the patient at least has an established connection with the CAR T-cell center.

Thomas G. Martin, MD:
Yes, absolutely, early referral is critical to improving access. Functional high-risk disease is particularly relevant in patients who have received a quadruplet regimen, undergone transplant, and then received maintenance therapy. Those patients who relapse within the first 3 years of quadruplet therapy represent functional high-risk disease. These patients are relatively uncommon, perhaps 10% or fewer relapse within the first 3 years, but they represent a particularly high-risk group. Those patients, in my view, are strong candidates for CAR T-cell therapy at that point in time. Alternatively, as newer studies such as the phase III MajesTEC-3 trial evaluating teclistamab in combination with daratumumab in early R/R MM show impressive data, these options may be more convenient for some patients. We will have to see how that evolves.

Carol Ann Huff, MD:
I would say that a patient who has more likely received a triplet regimen, followed by transplant and lenalidomide maintenance, and who relapses 7-10 years later is certainly someone we would want to have a conversation with about CAR T-cell therapy. However, I would not personally consider that patient to have functionally high-risk disease, although it is still important to engage him or her in a discussion about the treatment options.

Adriana Rossi, MD:
But that could potentially be a curative approach, right? I also think that so-called transplant-eligible patients are ideal candidates because this may truly be a one-and-done therapy. They may not need to return for the next line of treatment.

In transplant-eligible patients with newly diagnosed disease, given the measurable residual disease results from the phase III CASSIOPEIA trial with daratumumab-based induction and daratumumab maintenance, and the phase III PERSEUS trial with daratumumab plus bortezomib/lenalidomide/dexamethasone followed by daratumumab/lenalidomide maintenance, is it time to question lenalidomide maintenance and consider daratumumab-based maintenance instead?

Adriana Rossi, MD:
In my practice, I do that, but it is mostly based on patient preference. For many patients, maintenance therapy needs to include a component of the regimen that brought them into remission. When I present the options, many patients find daratumumab easier to continue than lenalidomide and choose it for maintenance.

Thomas G. Martin, MD:
I completely agree. In my practice, I typically follow the published protocol. There are some centers in the United States that use quadruplet induction, proceed to transplant, and then give single-agent lenalidomide maintenance without a CD38 antibody. However, we will not have randomized data to address this question until the phase III GMMG-HD7 study, which is evaluating isatuximab with bortezomib/lenalidomide/dexamethasone followed by lenalidomide maintenance with or without isatuximab. That study was first presented at ASH in 2021, and we still do not yet have data from the maintenance component, which really speaks to how well patients are doing overall. In my practice, I do use doublet maintenance with lenalidomide and daratumumab. For those in a deep response, I may ask patients if we are going to stop one agent, which do they feel is more toxic or less convenient for them, and I let the patients help guide that decision.

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