What are your top takeaways in Myeloma from ASH 2025?

As is probably true for most multiple myeloma-focused investigators, my interest was most piqued by the results of the MajesTEC-3 trial, which demonstrated an 83% 3-year progression-free survival in a population of patients with relapsed or refractory disease resulting from teclistamab and daratumumab in combination. Patients receiving this combination also had superior overall survival to those receiving the control arm (investigator's choice of Dara-Pd/Dara-Vd). This establishes a new standard of efficacy for RRMM trials and makes me optimistic about the future outcomes that will be seen with even earlier utilization of bispecific antibodies.

Despite the promising efficacy, however, this result has questionable applicability to the real wo...

The most clinically impactful MM studies in 2026 would be

1. MajesTEC-3
2. RediecTT
3. LimiTec

1. The top abstract undoubtedly was the Phase III MajesTEC-3 trial presented by Dr. Marivi Mateos, which demonstrated significant PFS and OS benefits with teclistamab & daratumumab (tec-dara) versus standard regimens in relapsed myeloma. Once this is approved, decision-making around BCMA CAR-T versus BCMA bispecific antibodies (plus daratumumab) at first relapse will get even trickier. NEJM publication for MajesTEC-3. Abstract: Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3
2. The second abstract, also with tec-dara, was the IFM 2021-01 t...

The presentation that will likely have the most immediate and far-reaching consequences would be MajesTEC-3. What was so noteworthy was the incredibly high response, depth of response, and durability. Many colleagues seem eager for the opportunity to use this combination. We will have to see if the infection rate in general practice is unacceptable in certain populations.

Along with this development, the LimiTec study abstract 5814 was interesting, as I think we would all like to limit bispecific engagers, but we are still figuring out how to do that.

Abstract #96, dealing with delayed neurotoxicity and peak ALC, confirmed what has been evolving practice, that this surrogate does seem to be associated with increased risk of neurotoxicity.

• The use of teclistamab + dara (MajesTEC-3 results) compared to DVD or DPD is very promising in first-line relapsed MM patients who are not candidates for CAR-T cells.
• COBRA study - use of carfilzomib in high-risk MM seems very promising, though the comparator arm only had velcade use for 32 weeks versus carfilzomib for 2 years.
• Iberdomide maintenance after auto SCT seems very promising - await EXCALIBUR Maintenance study results.
• t(11;14) - Myeloma is unique and should be considered intermediate risk and takes a longer time to achieve MRd negativity even with quadruplet dara VRD.
• High-risk criteria for myeloma are now defined as two high-risk abnormalities, except for p53-mutated MM.

1: Publication Number: 696 - Abstract Title: First 20-patient safety and efficacy data from NEXICART-2, the first U.S. trial of CAR-T in R/R light chain (AL) amyloidosis, NXC-201.

After daratumumab/bortezomib/cyclophosphamide/dexamethasone as first-line treatment, other regimens such as lenalidomide, pomalidomide, and carfilzomib are not tolerated well by many patients, even at lower doses.

CAR-T for myeloma, cilta-cel, and ide-cel are not being studied in AL amyloidosis, likely due to potential cardiac toxicity in patients who already have cardiac compromise from their AL amyloidosis.

With response rates of 60-70% in RRMM with CAR-T, it makes sense to have CAR-T for AL amyloidosis.

I love the fact that this is an off-the-shelf product. It ...

1. LBA-6 (MajesTEC-3): PFS and OS data were, of course, extremely impressive. This combination (teclistamab+daratumumab) will be a true competitor to cilta-cel in the lenalidomide-refractory, PI-exposed, population. This study shows the power of Tec-Dara, and while the change in practice to use of daratumumab/isatuximab upfront in both transplant eligible and transplant ineligible populations will mean that this combination will become less relevant over time as more patients progress on anti-CD38 mAb therapy, it also provides rationale for moving it up to the newly diagnosed [i.e., Abstr 367 (IFM2021-01)] or smoldering [i.e., Abstr 5775 (REVIVE)] settings.
2. LBA-1 (inMMyCAR). While clearly these data are extremely preliminary, the possibility ...

The late-breaking abstracts were the best. The in vivo gene therapy presentation could be practice-changing in delivering anti-BCMA T cells. The final one on teclistimab/Dara for myeloma was also significant.

1. MAJESTIC-3 study
2. In vivo CAR-T
3. Anito-cel

None has immediate practice-changing potential.

They could be practice-changing in the future. No immediate impact.

1. MajesTEC-3

This late-breaking abstract was the obvious top ASH highlight for most myeloma physicians, and for several good reasons. First, the relatively flat, almost Hodgkin lymphoma-esque progression-free survival (PFS) curve, reflecting an 83% 3-year PFS, is not something myeloma physicians are used to seeing in the relapsed setting. But beyond the appearance of the curve, the results are genuinely meaningful. Early use of teclistamab was associated with an overall survival benefit, and although it wasn’t entirely clear how many patients in the control arm ultimately received teclistamab, these outcomes are still superior to what has been seen with any bispecific antibody in the relapsed setting. This likely reflects the benefit of in...