Emerging Immunotherapies and Targeted Agents Advance Treatment of High-Risk Multiple Myeloma

Clinical Summary: 

• Paul Richardson, MD, discusses the evolving management of high-risk multiple myeloma, including genomic, clinical, and functional risk stratification and the integration of novel immunotherapies, targeted agents, and combination treatment strategies. 
• Emerging therapeutic approaches, including frontline quadruplet regimens, earlier immunotherapy integration, and CELMoDs such as iberdomide and mezigdomide, offer promising opportunities to improve outcomes in patients with high-risk disease. 
• These advances highlight the importance of identifying high-risk disease early and developing individualized treatment strategies, while underscoring the continued need for research to overcome the poor outcomes associated with high-risk multiple myeloma. 

Paul Richardson, MD, Dana-Farber Cancer Institute, Boston, Massachusetts, discusses advances in the identification and treatment of high-risk multiple myeloma, including emerging immunotherapies, targeted agents, and novel combination strategies, following his presentation at the 2026 Lymphoma, Leukemia & Myeloma Congress in New York, New York. 

Dr Richardson reviews the importance of genomic, clinical, and functional risk stratification in identifying patients with high-risk disease and discusses how frontline quadruplet regimens and earlier integration of immunotherapy may improve treatment outcomes. He also highlights emerging CELMoDs, including iberdomide and mezigdomide, and the potential for novel small-molecule therapies to address persistent unmet needs in high-risk multiple myeloma.

Transcript: 

Hello, everyone. My name is Dr. Paul Richardson, and I'm the clinical program leader and the director of clinical research at the Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute in Boston, Massachusetts. I also serve as the R.J. Corman Professor of Medicine at Harvard Medical School.

It's a real privilege to be here at the Lymphoma, Leukemia & Myeloma meeting in New York. It's an annual meeting that I thoroughly look forward to. This is the 26th year that this congress has been underway. It goes from strength to strength.

It's my privilege today to be part of a fabulous lineup of myeloma speakers and faculty with an excellent syllabus. My remit today was to discuss high-risk myeloma, which certainly is an incredibly important discussion because as we look to the incredibly important advances in myeloma therapy that have really contributed to improving prognosis for the majority of our patients, the reality is that for an important and significant subgroup, and it's as strong as 40% functionally as well as genomically, we are dealing with high-risk disease.

This is a very important area where outcomes for these patients are significantly different than for the majority. With that in mind, significant progress has been made. What I've done today is to talk about how we define high risk, both in genomic terms, clinical terms, and functionally, and how we meet that challenge with various therapies.

I think the most important thing to share with the audience today is the excitement around the newer therapies that are really beginning to help us make a dent on high-risk disease. These not only include immunotherapies, but also, very importantly, more targeted approaches in the small molecule space, which may be incredibly important in helping us beat this challenge.

A broad discussion today around therapeutic strategies that matter, both in the upfront setting with quadruplets, the use of immunotherapies early in the disease course, and at the same time the integration of exciting new molecules such as, for example, the CELMoDs, which have made such an impression this year, not least with the approval of iberdomide in August, but also the upcoming approval of mezigdomide, which I think adds a new dimension to our ability to take on high-risk disease.

In the conclusion of my discussion today, I really framed that there are important research advances that need to be continued to be met. I think it's very fair to say that high-risk disease remains one of the most important challenges in clinical research for myeloma today.

Hopefully, we're continuing to make progress in such a way that patient outcomes can be meaningfully continued to be improved over the next decade or so. But I think it's going to take that long to really make a dent on this because it is such a challenging entity.

Again, I'm very hopeful for progress. We share progress today. We discuss its implications, and we look to the future, recognizing that this is a substantial challenge on the one hand, but the toolbox, both in terms of identifying high risk and at the same time dealing with it, continues to grow. I just want to share my appreciation to the organizers for an excellent meeting. Look forward to continuing to contribute in years to come. Thank you.