How Are Personalized Frontline Multiple Myeloma Treatments Evolving?

In an interview with CancerNetwork^® at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition, C. Ola Landgren, MD, PhD, discussed how treatment selection in multiple myeloma is likely to become more individualized over the next 5 years as quadruplet regimens, CELMoDs, and T-cell engagers compete for a role in the frontline setting. Landgren traced the field’s evolution from a chemotherapy- and transplant-centered approach to one increasingly built around immunotherapy combined with small molecules, which he said can drive patients into deep, minimal residual disease (MRD)–negative responses regardless of traditional transplant eligibility status.

He argued that the more relevant clinical question going forward is not whether a patient is transplant eligible, but whether a patient needs transplantation at all, a shift he expects to accelerate as bispecific antibodies, CELMoDs, and other novel agents continue moving into earlier lines of therapy.

Landgren is a professor, chief of the Division of Myeloma in the Department of Medicine, director of the Sylvester Myeloma Institute, co-leader of the Translational and Clinical Oncology Program, and Paul J. DiMare Endowed Chair in Immunotherapy at the University of Miami Miller School of Medicine. He is also an editorial advisory board member of the journal ONCOLOGY®.

Transcript:

CancerNetwork: Quadruplets, CELMoDs, and T-cell engagers all now competing for a role in the frontline setting; how do you see treatment selection becoming individualized over the next 5 years?

The [multiple] myeloma field has been undergoing significant changes over the past several years. When I was in fellowship, it was all about chemotherapy, chemotherapy, and more chemotherapy. Part of that chemotherapy was the bone marrow transplantation. What has happened in more recent years is that immunotherapies have come in, and they’ve been partnered with small molecules. We see how these combinations can drive patients into a very deep treatment response—MRD negativity. We also see that this same pattern is found in patients traditionally called transplant eligible and transplant ineligible.

The whole idea with transplantation started in the United Kingdom almost 50 years ago, when delivery of a very high dose of chemotherapy was found to add [benefit] over just giving a low dose. For a long time, the field has split patients based on whether they can tolerate this or not; that’s what transplant eligibility is. A hot question today, and for the coming future, is: do we still need to do that? Do we still have to ask whether a patient is transplant eligible or not, and why do we have to decide that right away? I think a better question is: does the patient need transplantation? Instead of treating patients upfront and asking that question, you treat them with the best drugs we have, and if they achieve MRD negativity, maybe you don’t need to do a transplantation.

There are already studies. The phase 3 MIDAS study [NCT04934475], published in the New England Journal of Medicine, showed that whether or not you use transplantation, you have the same MRD negativity rates. The [adverse] effect profile is very much in favor of not using transplantation, and there are other studies as well. We will see more and more individualization using these concepts going forward, along with the new bispecific antibodies, CELMoDs, and other drugs coming for earlier lines. This is the beginning of a big shift in the field. The way I think about it is that we will move past the old terminology of transplant eligibility.

Reference

Perrot A, Lambert J, Hulin C, et al. Measurable residual disease-guided therapy in newly diagnosed myeloma. N Engl J Med. 2025;393(5):425-437. doi:10.1056/NEJMoa2505133