On Tuesday, June 17, the International Myeloma Foundation (IMF) conducted its annual webinar on the 2025 IMWG Conference Series: Making Sense of Treatment.  
 

The webinar was hosted by IMF Chief Medical Officer Joseph Mikhael, MD, MEd, FRCPC, FACP, FASCO (TGen at the City of Hope — Phoenix), along with myeloma experts, IMF Nurse Leadership Board Member Beth Faiman, PhD, MSN, APRN-BC, AOCN, FAAN (Cleveland Clinic, Taussig Cancer Institute — Cleveland); and member of the IMF Scientific Advisory Board and IMF Board of Directors, Sagar Lonial, MD, FACP (Winship Cancer Institute, Emory University School of Medicine — Atlanta).  
 
We continue with this two-part series, where the speakers presented on Early Relapse, Late Relapse, and the New Definition for High-Risk Myeloma.  
 
Here are some of the top takeaways from the topics mentioned above. We have gathered some of the key insights from this informative and insightful webinar. (EDITOR’S NOTE: Topics of discussion and panelist views have been edited for conciseness and clarity.) 
 

Early Relapse: Treatment Comparisons and Trends 

Dr. Mikhael elaborates on the following studies related to early relapse: 
 

IRAKLIA Study – On-Body Injector (OBI) for Isatuximab 

• Focus on delivery method, not efficacy 
• Sarclisa® (isatuximab) traditionally administed via IV; study introduces subcutaneous delivery via On-Body Injector (OBI) 
• OBI: 

             ◦ Small device taped to the skin 
             ◦ No direct needle handling; uses a 30-gauge needle 
             ◦  Administers drug over ~12–13 minutes 

• Study findings: 

             ◦ Comparable pharmacokinetics and efficacy to IV 
             ◦ No new safety concerns 
             ◦ Higher patient satisfaction with OBI 

• Potential future use: at-home administration 

 

DREAMM-7 Study – Belantamab Triplet vs. Daratumumab Triplet 
 

Comparison: 

• Blenrep® (belantamab) + Velcade® (bortezomib) + dexamethasone 
• vs. Darzalex® (daratumumab) + bortezomib + dexamethasone 

 
Key outcomes: 

• Median PFS of 36 months in belantamab arm 
• Median PFS of 21 months in high-risk cytogenetic subgroup 

 
Implications: 

• Belantamab likely returning to clinical use 
• Possible role for patients ineligible for or without access to CAR T-cell therapy 

 

CARTITUDE-4 Study – Carvykti® (Cilta-cel) vs. Standard Triplets 

• Study focus: one prior line of therapy and patients with extramedullary disease 
• Continued benefit of CAR T over triplet regimens across subgroups 

 

Lynozyfic™ (linvoseltamab-gcpt) – BCMA-Targeted Bispecific 

• Likely upcoming approval 
• Approved in several countries already 
• LINKER studies: 

              ◦ Linvoseltamab + Kyprolis® (carfilzomib) (MM2) 
              ◦ Linvoseltamab + bortezomib 
 
    •    Trend: increased use of bispecifics in combination regimens 
 

Key Takeaways 

• OBI: Innovative delivery method for isatuximab with potential for home use 
• Belantamab: Promising triplet results; likely to re-enter treatment landscape 
• Cilta-cel: Strong performance in early relapse and high-risk subgroups 
• Bispecifics: Growing role, with linvoseltamab leading upcoming combinations 

 
Dr. Mikhael: We're seeing more combination therapies with bispecific antibodies, which should help enhance their effectiveness. 
 
As for the On-Body Injector, I think it's a novel delivery method for isatuximab. While it may be a bit more complex to implement in the U.S., it opens the door to potential at-home administration, which could really improve convenience for patients. 
 
Belantamab is clearly making a comeback and will likely be available soon in triplet combinations. It’s already approved in several countries, and the big question now is where it fits: will it be used mainly for patients who aren't eligible for, or don’t have access to CAR T-cell therapy? 
 
And lastly, we’ll continue to see exciting data as more bispecifics enter the treatment landscape. 
 
Beth, what do you think about this OBI? Is this something beneficial for patients? 
 
Beth Faiman: I'm really excited about the On-Body Injector (OBI) for isatuximab. The IRAKLIA trial (and others) showed increased patient satisfaction. It followed the Isa-Pom-D regimen from the ICARIA study and showed similar response rates, around 71%, but what stood out was the improved patient experience. 
 
I saw a question in the chat about whether these studies are measuring quality of life and patient-reported outcomes—the answer is yes. That’s a big reason why I’m optimistic about this. 
 
The device uses a very small 30-gauge needle (like a diabetic needle) which is much less invasive than traditional options. From both a patient and nursing perspective, this could really simplify treatment. Just imagine patients coming in for a quick injection and taking their meds at home, instead of sitting through an IV infusion for a CD38 antibody. I think this is a great step forward, with more to come. 
 
Dr. Mikhael: Sagar, what do you think about belantamab and its resurgence? 
 
Dr. Lonial: I think both of those studies are really exciting, especially in terms of bringing BCMA-directed therapy earlier in the disease course. We've learned a lot about how to give belantamab. The dose and schedule can be flexible, depending on how the patient is doing. 
 
We’re also going back to ODAC in four or five weeks to push for getting belantamab back on formularies. Unlike last time, there’s less pressure to stick to an every-three-week schedule. If patients can tolerate that, great—but if not, they can still do just as well on a less frequent schedule. That’s important for both providers and patients to recognize— you don’t need to push out the maximum tolerated dose for this to be effective. It’s okay to tailor the timing based on symptoms. 
 
And you brought up the whisker plots for high-risk disease, which reminds me, I mentioned our carfilzomib, Pomalyst® (pomalidomide), and dexamethasone (KPd) high-risk maintenance approach. Dr. Ajay Nooka at our center ran a study using belantamab with pomalidomide and dexamethasone for high-risk patients. We’ve been using that for a couple of years now, and the data looks fantastic. The idea of BCMA-targeted therapy—especially one that doesn’t require frequent dosing—combined with something like pom is really raising the bar for patients across the board. 
 
Dr. Mikhael: I want to emphasize a really important point we touched on earlier—choice is always good for our patients. Different options resonate with different people. As you said, Sagar, when a patient walks in, some are okay waiting, while others want to act right away. That’s where options like CAR T or less frequent therapies come into play. 
 
You also mentioned something key: we rarely use any myeloma drug today, the way it was first introduced. There's a great paper led by Dr. Xavier Leleu, with Dr. S. Vincent Rajkumar as senior author, that questions whether we always need to push to the maximum tolerated dose—maybe we should aim for the minimally effective dose. We’ve changed how we use many treatments over time, including Bela, which we now give every 8–12 weeks in our clinic. Some patients only come in every three months—it’s remarkable. 
 

Late Relapse: Trispecific Antibodies and Other Promising New Treatments 

Dr. Mikhael clarifies the difference between early and late relapse in myeloma, breaks down the results of the CARTITUDE-1 trial, and introduces a promising new drug type—trispecific antibodies. He also talks about the RedirecTT-1 study (Talvey® /talquematab + Tecvayli® /teclistamab combo) and the new CAR T, anito-cel. 
 

Early vs. Late Relapse  

There's no strict line, but generally: 

• Early relapse = patients who have had 1–3 prior treatments (second, third, or sometimes fourth-line therapy). 
• Late relapse = patients who’ve already gone through several treatments beyond that. 

 
Key Study: CARTITUDE-1 (Cilta-cel)  

• Patients had an average of six prior treatments (very advanced disease). 
• They received just one dose of Cilta-cel (a type of CAR T-cell therapy). 
• Results: 

             ◦ 33% were disease-free at 5 years. 
             ◦ These were patients expected to live only about a year. 
             ◦ Described as one of the most impressive long-term results in myeloma. 
 

New Drug Type: Trispecific Antibody

What it is: 

• A step beyond bispecific antibodies (which target two parts: cancer cell and T-cell). 
• This new trispecific targets three: 

                ◦  BCMA and GPRC5D on the myeloma cell. 
                ◦ CD3 on the T-cell (to activate it) 
 
Why it’s exciting: 

• High response rates, especially in patients who hadn’t received BCMA or GPRC5D-targeting drugs before. 
• Over two-thirds reached complete remission or better. 
• Fewer side effects (like taste changes or weight loss) compared to similar drugs like talquetamab. 
• Likely helped by once-a-month dosing. 

 
Another Trispecific Update (From Australia) 

This version targets: 

• BCMA + CD38 on myeloma cells and CD3 on T-cells. 

Promising results: 

• Worked well in high-risk patients, including those with: 

             ◦ CAR T treatment. 
             ◦ Extramedullary disease (when cancer spreads outside the bone marrow). 

• Established dose now set. 
• Long half-life (17 days), meaning it doesn’t have to be given often. 

 

Talquetamab + Teclistamab Combo Study (RedirecTT-1 Trial) 

• Focused on patients with extramedullary disease. 
• Combination therapy (Tal + Tec): 

             ◦ 80% response rate 
             ◦ Much higher than either drug alone (which have around 40% response when used separately). 

Another Promising CAR T: Anito-cel (anitocabtagene autoleucel) 

First shown in December 2024, with a recent update. 

Results: 

• 97% response rate 
• Over two-thirds of patients reached complete remission or better. 
• At 1 year: 

               ◦ 80% progression-free survival. 
               ◦ 95% overall survival. 

• So far, fewer neurological side effects observed than Cilta-cel. 

 
Dr. Mikhael: The CARTITUDE-1 data is especially exciting—there’s more talk than ever about what a “cure” might look like. We're not there yet, but seeing a group of patients doing so well this far out is impressive. 
 
I also saw the new trispecific—it might hit that sweet spot of strong efficacy with fewer side effects, thanks to less frequent dosing. Another trispecific looks promising too, especially in extramedullary disease, which has always been tough to treat. Targeting myeloma in those hard-to-reach spots may really pay off. 
 
And now, with anito-cel, we’ve got a new CAR T on the horizon—not available yet, but it’s likely coming soon. 
 
Sagar, there’s a lot to digest. What’s your take? 
 
Dr. Lonial: The CARTITUDE-1 data is exciting, encouraging, and will dive into an important and evolving conversation—what does "cure" mean in myeloma? Even the updated response criteria will likely include a provisional definition— a big step toward creating a benchmark for future trials and reporting. 
 
What stood out most from the data you shared is the push toward using combinations of therapy—whether it's trispecifics with built-in targeting or external combos like in the RedirecTT-1 study. These approaches are key to eliminating resistant clones. The old model of sticking with a failing therapy just doesn’t hold up anymore. 
 
I'm also particularly hopeful about the role of CELMoDs. They could help reinvigorate exhausted T cells or generate more T and NK cells, potentially boosting the effectiveness of these immune-based treatments. So, the real question isn’t just whether to use BCMA before GPRC5D—but how to sequence or combine them in a way that sustains immune function and maximizes both depth and durability of response. 
 
Those are really going to be scientific challenges for us in the near future. Myeloma’s genetic complexity can feel overwhelming, but the fact that some patients in trials are seeing progression-free survival of 6 to 12 years tells us immune therapy can overcome that. We just need to be smart and strategic in how we combine and sequence these treatments. 
 
Dr. Mikhael: Historically, in myeloma, if Drug A gives a certain PFS and Drug B gives another, combining A and B often leads to even longer benefit—and we're seeing that same idea play out now with trispecifics. 
 
We’re getting very deep responses, maybe even deeper than before, but the key is to sustain them. Rather than giving a single bispecific, exhausting the T cells, taking a break, and then switching to something else, maybe we can use internal or external combinations upfront to keep T-cell function going longer. 
 
As Sagar put it, if we could build a “T-cell spa,” we’d do really well in myeloma. So, the goal is to find that sweet spot—strong enough to work, but gentle enough to avoid burning out the immune system. It’s a bit theoretical, but I really think that’s where we’re headed. 
Beth, what’s your take on this?  
 
Beth Faiman: I'm really excited to see that about a third of heavily pre-treated patients in the CARTITUDE-1 study are still MRD-negative. Maybe some of them reverted to MGUS, or the clone just isn’t detectable. Either way, it’s encouraging. We're now even talking about a potential cure—being off therapy for five years. Is that a cure for myeloma? It's a big shift. 
The trispecifics are also incredibly promising. We have the Tec + Tal study at my institution, and while combining therapies doesn’t always mean fewer side effects, the trispecifics are showing potential. You're balancing BCMA-related infection risks from teclistamab and GPRC5D-related skin and oral toxicities, but combining them might actually hit the tumor harder with fewer off-target effects. 
 
I’m especially intrigued by anito-cel. I love Carvykti and Abecma® (ide-cel), but seeing high response rates with anito-cel and fewer long-term neurotoxicities is exciting. For those of us who've been in this field a while, it’s amazing to watch what once felt like science fiction become reality. Now we face questions like: Do we need to keep patients on teclistamab every two weeks for 16 months, or can we pull back? That’s where real-world data—at ASH and other meetings—will really matter. 
 

A New Definition for High-Risk Multiple Myeloma 

Dr. Mikhael breaks down the new definition of high-risk multiple myeloma into five major factors. 
 
Key Points: 

• A new, more focused way to define high-risk multiple myeloma was introduced, aiming to better identify 20% of patients with the most aggressive disease, especially those who are newly diagnosed. 
• The definition includes five major factors: 

          1. Deletion 17p in at least 20% of the cells. 
          2. A TP53 gene mutation. 
          3. Biallelic deletion (both copies lost) of the 1p chromosome arm. 
          4. Beta-2 microglobulin over 5.5 with normal kidney function (normal creatinine), since kidney issues can affect beta-2 levels. 
          5. Having at least two of the following: 
                                ◦ A specific translocation (gene swap): t(4;14) or t(14;16) or t(14;20) 
                                ◦ A gain or amplification of 1q, 
                                ◦ A monoallelic deletion (only one copy lost) of 1p. 

• Why this matters: 

1. It helps narrow down the definition of "high-risk" to truly the most severe cases. 
2. Past definitions sometimes included 40–50% of patients, making "high-risk" less meaningful. 
3. This more precise approach could help target clinical trials and treatments specifically for the highest-risk group. 

• Challenges: 

1. Not all hospitals or labs can test for every marker (like TP53 mutations), though many of these can be detected with common tests like FISH. 
2. Even within this group, there's discussion about identifying an "ultra high-risk" category. 

Final thought: 
This is a step forward, but defining and treating high-risk myeloma remains a complex and evolving challenge. 
 
 
Dr. Mikhael: Sagar, I heard you talk earlier about your work with high-risk patients using KPd and belantamab/pomalidomide/dexamethasone. We've seen so many definitions of high-risk, and none are perfect. But this new approach helps narrow the focus. When 40–50% of patients are labeled high-risk, the term loses meaning. This definition gets us closer to identifying the truly highest-risk patients. Even within that group, we may need to think differently about those who fall into the "ultra" high-risk category. What’s your take, Sagar, since you've been closely involved in this? 
 
Dr. Lonial: The first thing I’ll say is I don’t fully trust outside genetics. The sample handling and testing methods aren’t always reliable. I still see reports where they’re not using CD138-selected or signal-enhanced FISH, which can lead to false negatives—a big problem. 
 
If I see patients early enough, I’ll often repeat the bone marrow biopsy myself, because getting accurate genetic data is critical, especially for deciding on maintenance therapy. While we use daratumumab with bortezomib + Revlimid® (lenalidomide) + dexamethasone (dara-VRd) for everyone up front, we tailor maintenance—often adding carfilzomib for high-risk patients—based on those results. 
 
Unless you’re at a major academic or myeloma center, the challenge is that the right tests are often not done. And now, with TP53 mutations becoming part of the high-risk definition, this gets even trickier. Personally, I trust NGS more than FISH for these mutations. Some NGS panels now give you translocations, mutations, and deletions—essentially everything we used to rely on FISH for. So, it’s important to work with centers that can run these comprehensive panels and get the data right from the start. 
 
Dr. Mikhael: You make a good point. We want the best definition possible but on the other hand, we want to make sure it's accessible. Because if it can only be done in a few centers, then it's a challenging definition. Beth, what do you think about this? 

Beth Faiman: High-risk myeloma is tough—especially when patients present with plasma cell leukemia or extramedullary disease. In the community setting, it makes sense to start with four-drug regimens, but as Dr. Lonial mentioned, getting a high-quality initial bone marrow biopsy is key. If your center can't do that, it's perfectly fine to partner with an academic institution. We often repeat marrows to get better data. 

We sometimes do sequential marrows, but outside of clinical trials, I see that as "nice to know" rather than "need to know"—it usually doesn’t change our treatment decisions unless the patient is clearly high-risk. 

That said, having the data might guide future choices. Ultra high-risk patients—those who relapse and respond quickly—are especially challenging. They'll likely need aggressive, combination and sequential treatments, including CELMoDs, BCMA-targeted therapies, and GPRC5D-based approaches. 

In case you missed it, you can still watch the replay of the June 17th IMWG Conference Series 2025 webinar. We have segmented the entire presentation into short videos by topic: Screening for Myeloma; Smoldering Multiple Myeloma; Frontline Therapy; Early Relapse; Late Relapse; and the New Definition for High-Risk Myeloma.