The Promise of CERVINO, MajesTEC-3, and EXCALIBER-RRMM in Multiple Myeloma

Al-Ola A. Abdallah, MD, pointed to 3 presentations from the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition that he believes could reshape care for patients with multiple myeloma. This included the phase 3 CERVINO trial (NCT06158841) of the BCMA-targeted bispecific antibody etentamig, which produced a lower rate of cytokine release syndrome (CRS) than historically seen with other bispecifics using a monthly, single step-up dosing schedule.¹ He also pointed to the phase 3 MajesTEC-3 trial (NCT05083169) of teclistamab-cqyv (Tecvayli) plus daratumumab (Darzalex), which showed an overall survival rate of 83.3% vs 65.0% with standard of care at 3 years in early relapsed disease.² Additionally, he highlighted the phase 3 EXCALIBER-RRMM trial (NCT04975997), which supported the first approval of a CELMoD, iberdomide (Zenbexus), using minimal residual disease (MRD)–negative complete response as an endpoint.^3.4

Abdallah, an associate professor of medicine and the director of the Plasma Cell Disorder Clinic in the Division of Hematologic Malignancies and Cellular Therapeutics at the University of Kansas Medical Center, spoke with CancerNetwork® about why these 3 presentations stood out to him and their potential to shift the multiple myeloma treatment paradigm, particularly in community oncology practices.

Transcript:

CancerNetwork: What other presentations from this year’s IMS meeting do you think have the potential to shift the multiple myeloma paradigm?

Abdallah: There were a lot of great presentations I was really interested in. I’ll summarize it in 3…The CERVINO trial, the phase 3 trial of monthly etentamig monotherapy, a BCMA-targeted bispecific antibody. I was very impressed by the results. I know there have been other bispecific trials, but this one included patients who received etentamig vs standard-of-care therapy in triple class-refractory multiple myeloma. I wasn’t necessarily surprised by the response rate—I was expecting a better response rate—but I was impressed by the CRS rate, which was lower than what we’ve historically seen with other bispecifics, at 28%. That’s impressive. There were no grade 3 [or higher] CRS, and ICANS [occurred] in less than 1% of patients. I was also impressed by the administration: a monthly bispecific given with a single step-up dose. I think this is going to be a major shift because community oncologists will need a drug like this, and I think this bispecific could be a good fit for a lot of community oncology practices. It is going to play a big role once it gets approval.

The MajesTEC-3 trial, teclistamab plus daratumumab, has also been talked about a lot. In early relapse, it showed an overall survival rate of 83.3% vs 65.0% at 3 years, and the nonrelapse mortality rate was not significantly increased with teclistamab/daratumumab compared with standard of care. I think this is critical [because] it establishes a new combination strategy using a bispecific plus daratumumab.

Another study that’s very important for community oncologists treating relapsed/refractory myeloma is the iberdomide study, EXCALIBER-RRMM. I think it’s very important to understand that this is the first study to gain approval using MRD-negative [complete response] as an end point, comparing iberdomide plus daratumumab-dexamethasone with daratumumab [plus bortezomib/dexamethasone]. The importance of that is also the new CELMoD drugs we’re going to be able to use in early relapse for patients who aren’t even candidates for CAR T-cell therapy or a bispecific, or who may have delays in receiving BCMA-directed therapy. I think these 3 trials are going to play a big role for oncologists and community oncologists as well.

References

1. Voorhees P, Mateos MV, Costa L, et al. CERVINO: phase 3 results of etentamig vs investigator’s choice of standard available therapies in patients with triple-class exposed relapsed or refractory multiple myeloma (RRMM). Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract LBA-01.
2. Costa LJ, Bahlis NJ, Perrot A, et al. Overall survival, progression, and non-relapse mortality with teclistamab plus daratumumab (Tec-Dara) vs dara-based triplets in relapsed/refractory multiple myeloma (RRMM): MajesTEC-3 post hoc analysis. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract OA-49.
3. Lonial S, Dimopoulos MA, Gavriatopoulou M, et al. Iberdomide, daratumumab, dexamethasone versus daratumumab, bortezomib, dexamethasone in patients with relapsed/refractory multiple myeloma: results from EXCALIBER-RRMM phase 3 study. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract LBA-12.
4. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. News release. August 13, 2026. Accessed October 12, 2026. https://tinyurl.com/38258auk