Consensus Viewpoints Offer Guidance in Rapidly Evolving Multiple Myeloma Management

As the multiple myeloma treatment paradigm continues to evolve and expand, the navigation of this landscape requires nuance and an understanding that emerging data will continue to reshape the space, according to Ajai Chari, MD.¹

“When I meet my patients now, I don’t spend too much time prognosticating. I’ll answer their questions, but what I say is, ‘What I tell you today will be obsolete in a year or 2 from now, because that’s how quickly the field is moving,’” Chari said. “That should give patients incredible hope for their future with myeloma, because it’s such an exciting time for clinical research in myeloma.”

Following the inaugural Bridging the Gaps in Leukemia, Lymphoma, and Multiple Myeloma Conference in 2025, Chari and colleagues published consensus recommendations for the management of multiple myeloma that emerged from the meeting.¹ During the meeting, 16 multiple myeloma experts from the United States offered 11 consensus recommendations across smoldering multiple myeloma, frontline therapy, transplant, maintenance, and relapsed/refractory disease management.

In an interview with OncLive^®, Chari outlined some of the key consensus viewpoints and recommendations featured in the publication.

Chari is a professor of medicine and director of the Multiple Myeloma Program at the University of California, San Francisco.

OncLive: With meetings like Bridging the Gaps, what is the importance of having opinions from different experts help inform treatment strategies and recommendations that could be applicable to clinical practice?

Chari: Many people look at the National Comprehensive Cancer Network Guidelines [NCCN] as a barometer of what [they] should do. The problem with that is [the guidelines are] a little overwhelming. I look at NCCN Guidelines as [an outline of treatment options that may be] insurance-approved, but when you have a table with 30 choices, how does that help you at the bedside?

Studies have shown that a patient with myeloma who has contact with an academic center has a better overall survival [OS]. Ideally, we would like to have partnerships where communities are working with academia. The goal of this paper is to try to give practical guidelines in areas that maybe don’t have a clear answer yet, [like for] community oncologists seeing 3 or 4 patients, [where some patients may not be able to travel long distances]. This kind of publication helps fill that gap [that remains with] current guidelines.

I’ll also quickly mention there is a lot of interest in artificial intelligence [AI]. Let’s say I'm giving a talk on a very current topic. AI falls apart at these data gaps. It cannot pull what we might have heard at a [recent] conference or saw in a poster. That’s where this kind of manuscript is helpful, because [some of these recommendations] are not yet in the NCCN Guidelines, and the data may not be in any other paper, so AI doesn’t help you.

Looking at the recommendations in multiple myeloma stemming from Bridging the Gaps, what were some of the key points regarding the management of smoldering myeloma?

The high-level problem with smoldering myeloma is that some patients have monoclonal gammopathy of undetermined significance [MGUS], and some have active myeloma. When you have this clinical definition without biological correlates, you’re throwing darts a little, and that’s why there’s a lot of uncertainty about what to do with this population. We now have data from the phase 3 AQUILA study [NCT03301220] to help guide this decision-making and give an option that’s generally well tolerated [with daratumumab (Darzalex)]. [Data] show a progression-free survival [PFS] and OS benefit [vs surveillance].² However, the [Bridging the Gaps] group could not reach a consensus on what we should be doing here, and I think it’s because of this heterogeneity. People wanted better risk definitions.

One of the problems with smoldering myeloma is, if you take a particular snapshot in time, that’s just a photograph. You need to understand the movie. What was happening prior to this visit? Where was the patient diagnosed? What’s happening after the initial diagnosis? A lot of us would like to see an evolving model incorporated, but AQUILA gives providers and patients an option, particularly for patients who might be older or have comorbidities. We’ll look forward to future versions of this meeting to see if the group is getting closer to a consensus on what to do with this complex topic [in smoldering myeloma].

Regarding the frontline setting for patients with active multiple myeloma, what was the consensus regarding up-front combination approaches and the role of autologous stem cell transplant (ASCT)?

Multiple phase 3 studies have shown that quadruplets are better than triplets, so that [recommendation] was a no-brainer. There’s a joke: If you ask 12 myeloma doctors, you’ll get 20 opinions. But on this, I think everybody agreed. The nuance is: Do frail or older patients need a quadruplet? That’s unclear.

Quadruplets are great, but because their efficacy is so good, the question is: Are we ready to forego ASCT? I don’t think we have a clear answer for that yet. [All patients] should still be considered [for ASCT]. For example, [some] excellent outcomes from quadruplet induction did include transplant.

Delving a little bit deeper into quadruplets, no one's doing twice-weekly bortezomib [Velcade], which is what the studies did, and that's important for practitioners to be aware of. Lastly, you can't say, on the one hand, quadruplet induction, transplant, and maintenance has a projected PFS of 13 to 20 years, and then say everybody needs prolonged, indefinite maintenance therapy. There's a lot of interest in stopping maintenance therapy in standard-risk myeloma with 2 consecutive minimal residual disease [MRD]-negativity [results]. I don't think we need to be giving people 17 years of therapy, and I think the group agreed that we should be starting to drill down on discontinuing therapy.

With the integration of CAR T-cell therapies, bispecific antibodies, antibody-drug conjugates (ADCs], and other combination strategies, in the relapsed/refractory multiple myeloma setting, what were some of the consensus view points on the treatment of this patient population?

We have pivotal phase 3 studies showing that BCMA-directed therapy has beaten standard of care [SOC], and it's important to highlight that these are not the historic triplet vs doublet [regimens]. SOC arms were, in fact, triplets. BCMA is beating SOC, and that's a big message to get across. We should be trying to move these therapies as early as possible, based on the indication and label.

Everybody [at the meeting] agreed, particularly for CAR T-cell therapy, that patients should be referred as early as possible, especially when we start having access to ADCs and bispecifics that could then affect the CAR T outcomes. We don't want to forego a great option for patients without at least having that conversation with the patient and their local doctor.

The other theme that's come up is, if a patient has had a BCMA-directed therapy, it's probably time to switch to a different target, like GPRC5D. Talquetamab-tgvs [Talvey] is [the only GPRC5D-directed agent currently approved for multiple myeloma], but there are other studies going on [with other agents].

With both CAR T-cell therapy and, importantly, bispecifics, when you're targeting BCMA, you get rid of myeloma, but you also get rid of normal plasma cells. Therefore, it's important to prevent infections with IVIG. We would [recommend] 6 months with CAR T-cell therapy and for as long as needed while on bispecifics, even going past that with BCMA-directed bispecifics and IVIG.

Since CAR T-cell therapy referrals require coordination with academic institutions and community practice, what is the importance of early referral?

If you look at, for example, ciltacabtagene autoleucel [cilta-cel; Carvykti], data have shown in advanced myeloma, [the CAR T-cell therapy generates a high] response rate [capable of] lasting 3 or more years with the treatment-free interval. However, from small datasets, the PFS after a prior bispecific targeting BCMA is only approximately 5 months, and after a prior [BCMA-directed] ADC, it is only approximately 9 months. To take a product [like cilta-cel] that is this good and also has cost, using it after these other therapies doesn't make sense from a clinical perspective, a patient perspective, a treatment-free interval perspective, or even a cost perspective.

We're not saying that everybody needs to get CAR T-cell therapy, but that conversation needs to happen at least, because if you get a BCMA-directed CAR T-cell therapy, there are other salvage options down the road that will work, [although] maybe still not as well.

That's the other theme that's come up. So far, it does seem like once you touch BCMA by any modality—ADC, bispecific, or CAR T-cell therapy—it does affect the next effort to target that same antigen, which is why we discussed target switch. What we need to understand more is how fixed-duration treatment or a treatment-free interval after an ADC, bispecific, and a T-cell boosting therapy [affect sequencing].

Right now, we don't have that data, so the message should be: pick up the phone. Call a community doctor, call your academic partner, and say, here's a patient scenario. Would you like to see this person, or should I start something else? As long as that conversation happens, then I think the community doctor can feel good about having checked that box, and then it's up to the referring provider to listen to the [patient and disease] factors that will help guide whether to move forward with an alternative [treatment] or to bring the patient in [for CAR T-cell therapy].

References

1. Chari A, Costello C, Krishnan A, et al. Integrating recent evidence and expert perspectives into the management of multiple myeloma: consensus recommendations from the 2025 Bridging the Gaps Conference. Am J Hematol. Published online April 21, 2026. doi:10.1002/ajh.70339.
2. Dimopoulos MA, Voorhees PM, Schjesvold F, et al. Daratumumab or active monitoring for high-risk smoldering multiple myeloma. N Engl J Med. 2025;392(18):1777-1788. doi:10.1056/NEJMoa2409029