Robert Orlowski, MD, PhD, MD Anderson Cancer Center, Houston, Texas, presented early data from the phase 1 LINKER-MM4 trial evaluating linvoseltamab, a BCMA-CD3 bispecific antibody, in newly diagnosed multiple myeloma at the 2025 ASH Annual Meeting & Exposition in Orlando, Florida.

At the recommended 200 mg dose, linvoseltamab achieved an 86% overall response rate with 43% complete responses and 95% MRD negativity, all with only mild, manageable toxicity. 

Dr Orlowski concluded, “These are the highest overall and complete and MRD-negative rates that we've seen for any single agent in the newly diagnosed setting. It really argues that it should be a either foundation drug for other combinations or maybe even used as a single agent in patients.”

Transcript:

Thank you for having me. My name is Robert Orlowski. I'm at the University of Texas MD Anderson Cancer Center, where I serve as the deputy chair for Lymphoma Myeloma and the Director of Translational Research for myeloma. 

I'm here at the ASH meeting to give you a preview of data we'll be presenting later on the LINKER-MM4 study, which is a phase 1 trial of the BCMA-CD3, bispecific T-cell engager, linvoseltamab for newly diagnosed myeloma. Right now, the standards of care in this setting are either quadruplet-regimens for transplant-eligible and for transplant-ineligible, fit patients or triplet regimens for more frail or older patients. But we still don't achieve 100% complete response rates and MRD or minimal residual disease negativity. 

Because linvoseltamab has had outstanding results in the relapsed/refractory setting where it is already FDA approved. We thought, therefore, to move it to the newly diagnosed setting because first of all, the myeloma should be more drug sensitive and second of all, the patient's T-cells should be fitter and healthier because they haven't been exposed to years of treatment.

This was a phase 1 with 3 different dose levels. We wound up identifying 200mg as the recommended dose for further study, which is the same dose that's FDA approved in the relapsed/refractory setting.

On the safety side, we did see cytokine release syndrome (CRS) in 44% of patients, but all of that was grade 1, which is the mildest grade, and there was only 1 event of ICANS, which is a neurologic toxicity. Interestingly, at the lowest dose also of grade 1 infections were seen, but only 1 third of those were grade 3. Almost all of them were sinus bronchial or pneumonia. There were 2 patients with CMV reactivation, again at the lowest dose level, and both of those were asymptomatic. Infections tended to decline over time, they were more prevalent in the first 3 months than later on.

The exciting part, if you look at the responses at the dose that was recommended, the 200mg, we had 86% of patients responding. That's intention to treat. 43% of those were in complete remission or better. We actually think those numbers will improve because many of those patients were still on treatment and hopefully their response will deepen further. If we look at the MRD negativity across the entire trial, there were 20 patients valuable who had at least a VGPR, 19 of those were MRD negative at either 10^{- 5 or 6}, so that's 95%. At the 200mg dose, again, all of the patients were MRD negative at both 10^-5 and 10^-6.

We, in summary, think that this is a very safe drug with no unexpected side effects in newly diagnosed patients. These are the highest overall and complete and MRD-negative rates that we've seen for any single agent in the newly diagnosed setting. It really argues that it should be a either foundation drug for other combinations or maybe even used as a single agent in patients. 

We are expanding the study further to get additional experience on both safety and efficacy to hopefully support some of those statements with more data. Thank you very much.

Source:

Orlowski R, Shah M, Chakraborty R, et al. Safety and efficacy of linvoseltamab as a simplified monotherapy first-line regimen in NDMM: Initial Results from the window of opportunity Phase 1/2 LINKER-MM4 trial. Dec 6-9, 2025; Orlando, FL. Abstract: 697