In a CancerNetwork^® Face-Off event, experts in the multiple myeloma field divided into 2 teams to discuss the efficacy, safety, and real-world considerations surrounding different cellular therapy modalities. The conversation focused on how CAR T-cell therapies in trials like the phase 3 CARTITUDE-4 study (NCT04181827) compare with bispecific antibodies, which have been evaluated in trials like the phase 3 MajesTEC-3 study (NCT05083169). The 2 teams: the Myeloma Mavericks, arguing in favor of CAR T-cell therapies, and the Myeloma Masters, representing bispecific antibodies. The teams competed across 3 domains: clinical trial updates, hot topics in the relapsed/refractory multiple myeloma space, and specific patient cases.

The discussion was moderated by Thomas G. Martin, MD, clinical research director of hematologic malignancies (blood cancers) at the University of California, San Francisco (UCSF) Helen Diller Family Comprehensive Cancer Center.

The Myeloma Mavericks included:

• Saad Z. Usmani, MD, MBA, FACP, FASCO, chief of the Myeloma Service at Memorial Sloan Kettering Cancer Center
• Surbhi Sidana, MD, associate professor of medicine and lead of the Myeloma CAR-T/Immunotherapy Program at Stanford University in California
• Gurbakhash Kaur, MD, assistant professor of medicine, Hematology and Medical Oncology at Mount Sinai

The Myeloma Masters included:

• Peter Voorhees, MD, professor of Cancer Medicine at Wake Forest University School of Medicine, and a hematologic oncologist at Atrium Health Levine Cancer Institute
• Amrita Y. Krishnan, MD, Nason-Hollingsworth Chair in Multiple Myeloma, executive medical director of Hematology at City of Hope Orange County, director of the Judy and Bernard Briskin Multiple Myeloma Center, and a professor in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope National Medical Center
• Hans Lee, MD, director of Myeloma Research at Sarah Cannon Research Institute

What is Face-Off? It is an educational program designed as a competition for teams to present to and against each other.

How does it work? There are 3 rounds: data presentations, hot topics, and patient cases. During each round, both teams can present and defend their ideas and challenge the other team. The judge determines who is worthy of the top prize.

Round 1: Data Presentation

The Myeloma Mavericks on CARTITUDE-4

Presented by: Saad Z. Usmani, MD, MBA, FACP, FASCO

In the phase 3 CARTITUDE-4 trial, patients with lenalidomide (Revlimid)-refractory multiple myeloma were assigned 1:1 to receive CAR T-cell therapy candidate ciltacabtagene autoleucel (cilta-cel; Carvykti; n = 208) or investigator’s choice of daratumumab (Darzalex) plus pomalidomide (Pomalyst) and dexamethasone (DPd) or pomalidomide plus bortezomib (Velcade) and dexamethasone (PVd; n = 211).¹ The trial’s primary end point was progression-free survival (PFS).

Overall, cilta-cel reduced the risk of progression or death by 74% compared with DPd or PVd (HR, 0.26; 95% CI, 0.18-0.38; P <.001). Additionally, the overall response rate (ORR) was 84.6% and 67.3% in the cilta-cel and standard of care (SOC) arms, respectively, which included complete responses (CRs) in 73.1% and 21.8% of patients. The minimal residual disease (MRD) negativity rate was 60.6% vs 15.6% in each respective arm.

Regarding cilta-cel’s safety profile, cytokine release syndrome (CRS) was predominantly grade 1/2, and immune effector cell-associated neurotoxicity syndrome (ICANS) was infrequent and manageable with standard protocols. Additionally, data showed a low incidence of serious adverse effects (AEs) with cilta-cel, and treatment-related mortality was comparable between arms.

The Myeloma Mavericks and The Myeloma Masters on Interpreting CARTITUDE-4

Martin: Team Mavericks, who is the best patient for CAR T-cell therapy in early-relapse disease? Who should get CAR T-cell therapy?

Kaur: Every patient with multiple myeloma at first relapse [should receive CAR T-cell therapy], taking several logistical considerations into account, is a perfect candidate because we see that early CAR T-cell therapy leads to deep and durable responses, and you have to start those discussions early on.

Martin: You talked a little bit about bridging therapy. Why is bridging important for these patients receiving CAR T cells?

Usmani: You have to take into account that autologous CAR T-cell therapy require logistics. You have to bring patients in, you have to leukapherese them, and you have to send those lymphocytes for manufacturing; all of that takes time. Patients have to come from the community to see us in the clinic; we have to get chair time for them, get the insurance approvals. All of that requires roughly a couple of months, so you have to control the disease during that time; this is where bridging is very important.

The second important thing we’ve learned is that we can mitigate a lot of the short-term as well as some of the long-term AEs of CAR T-cell therapy if we’re going in when the disease is controlled, not just taking off. Controlling the disease and making sure you’re not going in with high disease burden is an important key here.

Voorhees: I would like to point out a couple of pieces here. There is this immune effector cell–associated enterocolitis that occurs in some patients treated with this product, in about 2% to 3% of patients. At this point, there are no data that good disease control is going to mitigate that AE, which is a very severe AE and, in some cases, fatal. The other thing I’ll point out is that while parkinsonism definitely drops when you’re using cilta-cel in early relapse, it’s still about half 0.5%, we’re seeing more of the cranial nerve palsies and other neuropathies in this group of patients. Yes, they are reversible, [but] they can be quite troublesome. It can take weeks, sometimes several months, for those to resolve. If these AEs do occur, and they are important and serious, it can create significant challenges from a quality-of-life perspective.

Martin: Let me ask Team Masters: what other patient selection criteria would point you away from CAR T-cell therapy? Is there anything else that you look at and say, “This is not a candidate for CAR T-cell therapy?”

Krishnan: There are patients, for example, whose disease is growing too rapidly. You don’t have the manufacturing time to wait, and that’s the biggest consideration. Patients need a lot of support in terms of the logistics of CAR T-cell therapy.

Martin: Team Mavericks, I’ll let you have the closing argument about CARTITUDE-4 and quality of life. What’s the quality of life like?

Sidana: The quality of life for patients who got this 1-time cilta-cel infusion after bridging therapy is excellent. It’s better than the standard-of-care arm, where patients got continuous therapy. Maybe in the first 2 to 4 weeks there’s a slight decline, but it rapidly increases to better than baseline. This is not just [in the] data; this is our patients’ lived experience every day. They’re able to travel the world, they’re able to enjoy their family, and they’re back to being regular humans.

The Myeloma Masters on MajesTEC-3

Presented by Amrita Y. Krishnan, MD

As part of the phase 3 MajesTEC-3 study (NCT05083169), 587 patients with 1 to 3 prior lines of treatment for relapsed/refractory multiple myeloma were assigned to receive the bispecific antibody teclistamab-cqyv (Tecvayli) in combination with daratumumab (n = 294) or investigator’s choice of DPd or daratumumab plus bortezomib and dexamethasone (DVd; n = 293).² The trial’s primary end point was PFS.

Efficacy data showed an 83.4% reduction in the risk of progression or death with the teclistamab-based combination vs SOC therapy (HR, 0.17; 95% CI, 0.12-0.23; P <.0001). The 36-month PFS rates were 83.4% and 29.7% in the experimental and SOC arms, respectively. The teclistamab regimen also improved overall survival (OS; HR, 0.46; 95% CI, 0.32-0.65; P <.0001). In the experimental and SOC arms, respectively, the ORRs were 89.0% vs 75.3%, the very good partial response (VGPR) or better rates were 86.6% vs 57.1%, and the MRD negativity rates were 58.4% vs 17.1%.

Selected safety data showed that 78.4% of patients in the teclistamab arm experienced any-grade neutropenia, while 75.6% had grade 3/4 events. Any-grade and grade 3/4 events, respectively, also included hypogammaglobulinemia (68.6%, 5.7%), CRS (60.1%, 0%), diarrhea (51.9%, 3.5%), COVID-19 infection (43.8%, 6.0%), and pneumonia (23.0%, 16.6%).

The Myeloma Mavericks and The Myeloma Masters on Interpreting MajesTEC-3

Martin: I’ll ask Team Masters: this population was essentially naive to daratumumab, right? The majority of patients never received daratumumab. Do we have that population in the US? Who do you think you would choose for this therapy?

Lee: We have a proportion of patients who are daratumumab naive. We have these patients who [received] induction with triplet-based induction with bortezomib, lenalidomide, and dexamethasone [VRd], [received a] transplant on lenalidomide-based maintenance, and have had 5 to 7 years of durable response. Maybe they’re progressing at this point, and that would be a patient population relevant to MajesTEC-3.

Martin: In CARTITUDE-4, more than 60% of patients had adverse cytogenetics, but in this study, it was just over 30%. Does that make a difference in terms of patient selection? Would you rather take the patients who have high-risk cytogenetics and do CAR T-cell therapy, or would you still do teclistamab/daratumumab?

Voorhees: The important thing here is that when you look at the subsets of patients, whether it was cilta-cel or teclistamab with daratumumab or whether you had standard-risk or high-risk cytogenetics, the HRs for PFS and OS were very similar. I don’t think high-risk cytogenetics would push me toward one vs the other.

Martin: Dr Krishnan, you talked about IVIG support. What do you do in this patient population?

Krishnan: Yes, supportive care is very important and key to the success with bispecifics, and certainly a part of that is use of IVIG to keep the levels maintained to minimize risk of infection. They do need to continue IVIG for as long as they are on bispecific antibody treatment.

Martin: In both therapeutics, the infection risk is highest in the first 3 months, and then they both [decrease] over time. Dr Lee, can you tell us a little bit about the cytopenias with bispecifics and how you manage those?

Lee: You can get transient neutropenia and cytopenias with the step-up dosing due to inflammation and the CRS, but it’s very transient. With de-escalation of the frequency of dosing, it goes away quickly. I don’t think there’s a risk for prolonged, irreversible cytopenias, typically, with bispecifics. Patients who go in with high disease burden, which we typically don’t do anymore with CAR T, still have this risk for prolonged cytopenia, and I do get concerned that if I have a patient without stem cells in storage, in that less-than-5% case, that could be a challenge.

Krishnan: The magic of MajesTEC-3 is that it is available to anyone in the community. It can be delivered, and that’s what we want: treatment that every patient with multiple myeloma can get. They can get teclistamab/daratumumab.

Kaur: Can I add to that? It’s also a myth that both bispecifics and CAR T are accessible to everyone. If we look at the data, the community still has not ramped up efforts in terms of getting bispecifics going. The ramp-ups still have to be done at academic centers, and not all the community practices out in the country are ready to receive the patients and the supportive care involved. The work that’s needed to get access…needs to be done for bispecifics too.

Voorhees: You’re right, but I would argue that community oncology practices are positioned to be able to implement bispecific antibody therapy. You’re not going to get a small community oncology practice certified to deliver CAR T-cell therapy. The promise of accessibility is better with the bispecific antibodies as opposed to CAR T-cell therapy. You are right: we need to do better because most patients are not gaining access even to the bispecifics today.

Round 2: Hot Topics

The Myeloma Mavericks on Using CAR T-Cell Therapy Before Bispecific Antibodies

Presented by Saad Z. Usmani, MD, MBA, FACP, FASCO

Our position is that early use of CAR T-cell therapy is the best bet for patients in the relapse situation, and this is based on concrete data. When I’m in clinic talking to patients, the only therapeutic we have in our armamentarium that has demonstrated curative potential already in the late-relapse setting is cilta-cel. Based on the CARTITUDE-4 data, that is the best option we have. We have deep, durable responses. Yes, we have early AEs with these therapies, but the bounce-back for patients is outstanding; it’s better than transplant, better than anything else we have, and the patients have amazing quality of life. They’re not bogged down at the infusion center on a monthly or biweekly basis getting IVIG or treatments forever. One of the things we always downplay about bispecifics is the infection risk, and that is such a detriment to quality of life. They’re always tied to the cancer center. You don’t have to do that with CAR T. It is one and done, and it is the GOAT. You don’t keep Michael Jordon [MJ] for the last quarter of the game; you bring him on the first time.

The Myeloma Masters on Using Bispecifics Before CAR T-Cell Therapy

Presented by Peter Voorhees, MD

It’s important to note that we have 2 Michael Jordans on our basketball team, to be perfectly honest. When you look at the PFS and OS with both the MajesTEC-3 and MajesTEC-9 [NCT05572515] studies, it compares very well to CARTITUDE-4.³ From an efficacy standpoint, whether you’re looking at PFS or OS, daratumumab with teclistamab, or teclistamab alone, is performing on par with cilta-cel. That’s the bottom line. You have to look at other features when deciding.

When you look at safety, you are right; there is a higher rate of high-grade infection. If you have a patient whose clinical course has been dotted by frequent high-grade infections, cilta-cel may be a better option. Thankfully, most of our patients don’t fall into that category. [Additionally], with the bispecifics, you don’t have to worry about these quirky delayed neurotoxicities, and you don’t have to worry about the enterocolitis; an increased risk of secondary hematologic malignancies hasn’t emerged yet, but we do have to keep a close eye on that. From a safety perspective, on balance, it argues in favor of the bispecifics.

When we look at accessibility, all of us agree that access to both therapeutics is limited even in the US, and that has to change. Bispecific antibody therapy is poised to be more accessible relative to CAR T-cell therapy, and the caregiver demands in the early period are far less onerous for patients getting step-up dosing than for the person who has to determine whether their loved one has a personality change over the first month or 2 after receiving CAR T-cell therapy. There are a lot of practical considerations that lean in favor of bispecific antibody therapy. The other thing is if you’ve got a patient whose disease is taking off very quickly, you may not have the ability to get to CAR T-cell therapy. Now, with more effective holding and bridging strategies, that’s less of a current concern in the early-relapse space, but if you have someone becoming sick quickly, an off-the-shelf option you can give within a week has a lot of advantages.

The Myeloma Mavericks on Improving Mitigation Strategies for Toxicities After BCMA-Directed Therapy

Presented by Gurbakhash Kaur, MD

If I think CAR T-cell therapy is the destination, I try not to expose that patient to a BCMA-directed therapy first, whether that’s belantamab mafodotin-blmf [Blenrep] in combination with other agents, or a bispecific. Sequencing matters, and I know much of the data have been generated in later lines, but antigen escape and T-cell fitness remain a question even in early lines. For the patient where CAR T-cell therapy is the destination, I will hold therapy with other agents before I select CAR T because I do not want to impair the T-cell fitness. That plays a big role in my day-to-day decision-making.

CAR T-cell therapy is the C-word: cure. MJ can come off the bench, still dunk and score 40 points…and win the game. CAR T-cell therapy is efficacious, and I try to fit that into my patient’s treatment paradigm wherever I can.

The Myeloma Masters on Patient Selection and Long-Term Safety Considerations for BCMA-Directed Treatment

Presented by Amrita Y. Krishnan, MD

It is a calculus, and to be fair to what Dr Voorhees said, both are very valid, important treatments for patients. I divide it into a couple of things. No 1, we’ve already talked extensively about patient selection and infection risk. Certainly, infection risk is higher with bispecifics because of the long-term exposure to continuous therapy, which, as he said, will change. I don’t want to downplay that CAR T-cell therapy has infection risk, but it’s time-limited in that first 6 months; it is there, though.

Second, in terms of the other toxicities, this is where it becomes more nuanced. Dr Sidana talked about neurologic toxicity. I don’t think cyclophosphamide is effective in all cases; it’s effective only in about 50% of patients, and only if you start it extremely early. If our hope with CAR T-cell therapy is also more accessibility [and getting] patients back to the community earlier, good luck seeing a neurologist, even in an academic center, let alone in the community, in an urgent, instant fashion to evaluate those toxicities. The same with immune effector cell-associated colitis; we think recognizing it early gives you the best chance of success, and as these patients go out into the community, recognizing that toxicity is a leap of faith. To be fair, the onus is on us to educate our colleagues to make that better.

Round 3: Patient Cases

Managing Earlier-Relapse Multiple Myeloma With Rapidly Progressive Disease

Presented by Thomas G. Martin, MD

A 61-year-old patient with relapsed/refractory multiple myeloma presents after progressing on lenalidomide maintenance therapy following upfront transplant. The patient is demonstrating rapidly progressive disease with worsening anemia, bone pain, rising light chains, and high-risk cytogenetics. The patient is otherwise fit, with an ECOG performance status of 1, but requires prompt initiation of therapy due to the symptomatic nature of the disease. The question is, what factors are most important when selecting therapy here? Is it cytogenetics? How fast are they progressing? What is the role of logistics, referral timing, and treatment accessibility?

Sidana: This is a practical scenario that happens in clinic all the time. We have to consider that this is a rapidly progressing patient who needs disease control. If this patient is already at a treatment center because [they have] already gotten a transplant and already plugged into a center that does CAR T-cell therapy, then hopefully, if possible, I could do apheresis next week and start this patient on bridging therapy, something like daratumumab plus carfilzomib [Kyrpolis] and dexamethasone [DKd] in this aggressive patient. If this patient is in the community, I would tell my community partner to start them on holding therapy because we know there are certain holding therapies that can impact apheresis, like bispecifics or bendamustine [Treanda] or some cytotoxic therapies. Daratumumab, immunomodulatory drugs [IMiDs], and carfilzomib don’t do that, to our knowledge. I would give DKd, either as bridging immediately after apheresis or as holding, and then take them to apheresis later.

Martin: [The Myeloma Masters], what do you think about this case for bispecific therapy?

Voorhees: The fact that the disease is advancing quickly…is probably not that relevant when you’re choosing CAR T-cell therapy vs a bispecific antibody. As Dr Sidana said, DKd would be a very good strategy to start controlling their disease as you’re having the conversation about CAR T-cell therapy vs bispecifics. It comes down to a discussion with the patient about the logistics of administration, the safety signals, and the pros and cons of the 2 approaches. Then, you come to a decision. For this patient, the daratumumab/teclistamab data look amazing, and the cilta-cel data look amazing, so it’s a win-win from an efficacy perspective. It comes down to operational, logistical considerations and safety.

Using Advanced Immune-Based Therapy in Second-Line Relapsed/Refractory Disease

Presented by Thomas G. Martin, MD

[This is] a fit patient eligible for immunotherapy in the second line. A 58-year-old patient, who is lenalidomide refractory, presents with biochemical and radiographic progression after frontline therapy. They’re relatively asymptomatic, disease burden is currently controlled, and the patient is considered an appropriate candidate for either CAR T-cell therapy or bispecific therapy. However, concerns remain regarding the timing of treatment, bridging therapy, and potential toxicity risks. How do you discuss which therapy [to use for] this patient, where there’s no rush to therapy?

Kaur: This is, in fact, the perfect patient for CAR T-cell therapy. They’re young, they’re fit, and they’re plugged in and wanting to understand the risk factors associated with both types of therapies. At 58 years of age, we want to give them another 20 years, and sequencing of immune therapies matters the most here. I will harp on the fact that T-cell fitness and antigen loss influence my decision. If we’re ready to make the decision about CAR T-cell therapy, I would apherese them and give them bridging therapy to control the disease as much as possible because I’m not in a rush; this is not aggressive disease. If [might] takes a cycle or 2 or even 3; I used to only do 1 cycle, but what’s the rush when they’re responding? Then, [I would] take them to CAR T-cell therapy so they hopefully don’t relapse and are part of that cure fraction. You’re able to give this young 58-year-old treatment-free interval time. Then, if and when they relapse, talquetamab-tgvs [Talvey], teclistamab, and other CAR T-cell therapies may be available at that time.

Lee: I would say the stem of this case was that the patient was concerned about the logistics of CAR T. Is that correct?

Martin: Well, they just want to know more about it.

Lee: This is where we can individualize patient treatment. We discuss what is feasible at the time and what’s not. Bispecifics, being off-the-shelf and easy to give, could be an option for this patient as well.

Martin: In a young patient with slowly progressive disease, what would be your favorite therapy: CAR T-cell therapy or bispecifics?

Krishnan: This is not as easy as you think because, again, the risk is small, but the consequence is great, in a disease that’s going to respond to either treatment. What you have to do is be honest with the patient and say, “This is the risk; it’s small.” I will never tell a patient I can control their movement and neurocognitive toxicities [MNTs] and be consistent and sure of that; I’ll say the risk is very small. You help them understand. Some patients are risk-takers, and others are risk averse.

WINNER: The Myeloma Mavericks

References

1. San-Miguel J, Dhakal B, Yong K, et al. Cilta-cel or standard care in lenalidomide-refractory multiple myeloma. N Engl J Med. 2023;389(4):335-347. doi:10.1056/NEJMoa2303379
2. Costa LJ, Bahlis NJ, Perrot A, Teclistamab plus daratumumab in relapsed or refractory multiple myeloma. N Engl J Med. 2026;394(8):739-752. doi:10.1056/NEJMoa2514663
3. Touzeau C, Mina R, Hungria V, et al. MajesTEC-9: a phase 3 study of teclistamab monotherapy vs pomalidomide/bortezomib/dexamethasone or carfilzomib/dexamethasone (PVd/Kd) in patients (Pts) with relapsed refractory multiple myeloma. Presented at: European Hematology Association Annual Meeting; June 11–14, 2026; Stockholm, Sweden. Abstract S195.