Real-World CAR T Data for Extramedullary Patients

There is a strong need for durable, deep-response-inducing treatment for extramedullary multiple myeloma patients. 

While immunotherapy treatments (such as CAR T-cell therapy) significantly improve the outcomes of several myeloma patients, can the same be said for those with extramedullary disease? 

What is Extramedullary Disease?

In the video below, Dr. Amrita Krishnan, a multiple myeloma specialist from City of Hope, explains the definition of extramedullary disease and why it’s considered high-risk. 

The current treatments for multiple myeloma are excellent at targeting the bone marrow. However, multiple myeloma cells often lose their adhesive molecules over time, which keep them in the bone marrow, and migrate to other parts of the body, including the liver, chest, and brain. 

The aggressive nature of extramedullary multiple myeloma classifies it as high-risk. 

What is CAR T-Cell Therapy?

In the video below, three multiple myeloma specialists explain CAR T-cell therapy, how it works, and the potential side effects that might result from it. 

CAR T-cell treatment is one of the most advanced forms of immunotherapy. A patient’s cells are collected, reegineered in a lab so they can recognize myeloma cells, and then infused back into the patient. 

While CAR T-cell treatment has existed for around a decade in various diseases, it’s relatively new to the myeloma treatment field. As of June 2024, there are two CAR T-cell therapies approved to treat multiple myeloma. They are ciltacabtagene autoleucel (CARVYKTI, Johnson&Johnson) and idecabtagene vicleucel (Abecma, BMS).

Ide-cel Treatment Analysis in Extramedullary Patients 

An abstract shared at the 2024 ASCO (American Society of Clinical Oncology) Conference shared observations of extramedullary patients who had undergone the Idecabtagene Vicleucel (also referred to as ide-cel or Abecma) CAR T-cell therapy. Researchers included patients from 11 U.S. academic centers who fit this criteria between May 2021 and April 2023. 

Cohort Details 

This cohort included 351 patients treated with ide-cel:

• 84 patients had extramedullary disease (EMD), meaning that there were soft tissue masses or lesions outside of the bone.
• 267 patients had paraskeletal disease, meaning their soft tissue masses were still connected to their bones or there were no detectable soft tissue masses (non-EMD). 

Patients with EMD were younger than those included in the non-EMD group, but their overall health status was worse.  

Observations and Outcomes 

After following up on these patients for 18 months after the infusion of the CAR-T, the researchers observed that:

• Fewer patients in the EMD subgroup responded to the treatment.
• Those who responded had less deep and less durable responses than patients without extramedullary disease.
• The median progression-free survival (PFS) for those with extramedullary disease was 5.3 months. This means that for half of the patients, the time from ide-cel infusion to the day the patient’s disease progressed was 5.3 months or shorter. 
• PFS was very similar across the whole cohort of patients with extramedullary disease, regardless of the number of lesions and their location.
• Regarding ide-cel side effects, patients with EMD experienced higher rates of blood cell count decreases, particularly serious lower levels of neutrophils, a white blood cell that helps fight infections. This could have also led to a higher incidence of infections.

If you are a visual learner and would like to see a table of the results, look here: EMD vs non-EMD Results

Study Conclusion 

After adjusting for multiple variables, the researchers concluded that extramedullary disease was an independent predictor of poorer responses and a shorter progression-free survival after receiving ide-cel CAR T therapy. 

Conclusion

Unfortunately, as previously reported in multiple studies, BCMA-targeted CAR T-cell therapy does not seem to be the breakthrough extramedullary disease patients and their loved ones seek. 

However, it still remains an available treatment option for those who need another line of therapy and could potentially lead to a remission of several months. 

Thankfully, we are seeing an increase in clinical trials designed with extramedullary disease and other high-risk features in mind. The field is more active than ever, so the breakthrough for extramedullary disease could be right around the corner. 

Action Steps 

Stay informed about potential treatments for extramedullary myeloma patients through the following resources.

• HealthTree University (Myeloma Therapy Courses)
• HealthTree News for Multiple Myeloma (Treatment advances subsection) 

Sources: 

• Impact of extramedullary multiple myeloma on outcomes with idecabtagene vicleucel 
• Understanding Outcomes of CAR T Cells in Multiple Myeloma: Insights from ASH 2023 Interview with Dr. Darren Pan
• Can CAR T Benefit Extramedullary Disease? - HealthTree for Multiple Myeloma