Key Advances in High-Risk Multiple Myeloma

Multiple myeloma research continues to evolve, especially for people with high-risk disease. Studies are improving how doctors define risk, when treatment should begin, and how new therapies can help control the disease longer. These advances may help patients and care teams make more informed treatment decisions throughout the myeloma journey.

The evolving definition of high-risk multiple myeloma

Last year, a new definition of high-risk multiple myeloma drew significant attention from both patients and specialists. Risk status is important because it helps doctors guide treatment decisions and set realistic expectations about how the disease may behave.

This updated definition also emphasizes the need to reassess myeloma regularly. Over time, patients may develop new high-risk features. By checking risk status throughout the disease course, doctors can adjust treatment plans earlier if the disease becomes more aggressive.

Keep reading this article here.

High-risk smoldering myeloma treatment now approved 

For many years, people with smoldering myeloma followed a “watch-and-wait” treatment strategy. They had abnormal plasma cells but no approved treatment designed specifically for their condition.

In November 2025, the U.S. Food and Drug Administration (FDA) approved daratumumab to treat high-risk smoldering myeloma with certain genetic features. This approval was based on a clinical study comparing the traditional watch-and-wait approach with treatment using daratumumab.

The results showed that treatment with daratumumab reduced the risk of disease progression by 51% compared with observation alone. This marks an important shift toward treating some patients earlier to delay or prevent active myeloma.

Read the article that expands on how daratumumab works for high-risk smoldering myeloma here.

Do infections become more common in myeloma as it progresses?

People with high-risk myeloma are more likely to experience relapse after a period of treatment. When myeloma returns or stops responding to therapy, doctors often need to adjust the treatment plan or switch to a new approach.

Relapse may also increase the risk of infections. A recent study found that patients with relapsed or refractory myeloma have a higher chance of developing infections. This may happen because the disease and some treatments can weaken the immune system.

Understanding this risk can help patients and care teams take preventive steps and monitor symptoms closely.

Read more details about this article here.

Teclistamab and daratumumab combination for relapsed multiple myeloma

Many people with high-risk myeloma receive several different treatments during their disease journey. This new combination was recently approved with the goal of helping control the disease longer after relapse. 

Results from the phase 3 MajesTEC-3 clinical trial showed that combining teclistamab with daratumumab may significantly improve outcomes for people with relapsed or refractory multiple myeloma who have already received one to three prior treatments.

Compared with standard treatment options, the Tec-Dara combination reduced the risk of death by 54% and kept the disease from worsening for a longer period of time. The treatment also led to higher complete response rates and higher minimal residual disease (MRD) negativity rates, meaning fewer myeloma cells could be detected after treatment.

Read more details about the MajesTEC-3 trial here.

High-Risk features linked to earlier relapse after cilta-cel treatment

A large multi-center study of 598 patients with relapsed or refractory multiple myeloma treated with the CAR T-cell therapy ciltacabtagene autoleucel (cilta-cel) found that although most patients respond well, some experience relapse within the first 18 months after treatment. 

Researchers identified key risk factors linked to earlier relapse, including functional high-risk disease (relapse within 18 months of starting first-line therapy) and high-risk genetic features defined by the adapted IMS-IMWG criteria, both of which were associated with shorter progression-free survival. Patients without high-risk features had higher response rates and better 12-month progression-free survival compared with those who had at least one risk factor. 

Analyzing high-risk myeloma brings new insights into how it can be treated 

From better definitions of high-risk disease to earlier treatment strategies and new immunotherapy combinations, these advances are expanding the options available to patients. For people living with high-risk myeloma, staying informed about new research can help guide conversations with their healthcare team. 

Stay tuned for more news and don’t miss any of our educational content. Receive alerts with weekly highlights by subscribing to our Myeloma Newsletter and become a part of our community built by patients, for patients. 

SUBSCRIBE TO NEWSLETTER

Source: Predictors of early relapse following ciltacabtagene autoleucel: Informing risk-adapted therapy in relapsed/refractory multiple myeloma