ASH Annual Meeting 2025 Day 2: New Data Show Lasting Responses with CAR T and Oral Therapies

Today’s update from the 2025 ASH Annual Meeting highlights new and existing therapies that could improve care for patients at all stages of multiple myeloma. Read the key takeaways below, and be sure to catch up on the first day.

For a deeper dive into the most important findings from ASH, join us for our Conference Highlights Webinar on December 17. Register here.

For day 2, ASH presentations focused on existing therapies and asked two very important questions: 1) how well do they work, and 2) what can be done to improve them?

Answering this first question, new data covering the effectiveness of Isa-VRd (Sarclisa, Velcade, Revlimid, and dexamethasone) in different patient populations was presented, as well as updated data on Carvytki (cilta-cel), a CAR T-cell therapy that shows strong potential for providing long-lasting disease control for patients whose myeloma has relapsed.

To answer the second question, researchers presented on CELMoDs, a new class of oral therapies designed to enhance the immune response in myeloma. Studies showed encouraging results when CELMoDs were paired with different treatments across various stages of the disease.

New data support the use of Isa-VRd as a standard of care in newly diagnosed patients, with potential impact on quality of life

New data from a Phase 3 study suggest that Isa-VRd is more effective than Isa-Rd in treating older, high-risk NDMM patients who cannot undergo a stem cell transplant. As a reminder, Sarclisa is a monospecific antibody, similar to Darzalex.®

The study included over 200 patients aged 65–79 with high-risk disease features, such as certain genetic changes or high levels of a blood protein called β2-macroglobulin. Results showed:

• Thirty-one percent of Isa-VRd patients became MRD-negative compared to 13 percent of Isa-Rd patients.
• Isa-VRd patients were more than twice as likely to achieve MRD negativity.
• No new or unexpected side effects were reported.

Another study highlighted the impact of Isa-VRd treatment on quality of life. In over 600 newly diagnosed patients who were eligible for a stem cell transplant, Isa-VRd was linked to pain reduction, improved fatigue, and overall favorable quality of life compared to VRd alone.

IsaVRd is currently FDA-approved in the U.S. for NDMM patients not eligible for a stem cell transplant. However, some patients may access IsaVRd off-label, meaning it is used in ways not specifically approved by the FDA, based on a doctor’s judgment. Talk to your care team to see if IsaVRd may be an appropriate option for you.

Carvykti^® keeps multiple myeloma under control for longer than standard 3-drug therapy

A large, Phase 3 study concluded that a single infusion with the CAR T-cell therapy Carvykti helped keep multiple myeloma under control longer than a standard 3 drug therapy, offering promise as an earlier treatment option for patients with relapsed/refractory myeloma. In this study, Carvykti was compared to two standard regimens: PVd (Pomalyst®, Velcade®, and dexamethasone) or DPd (Darzalex®, Pomalyst®, dexamethasone). Even after 2.5 years, three out of four patients treated with Carvykti still had their disease under control, compared to less than half of those treated with standard therapies. No new side effects were reported.

These data suggest Carvykti can provide safe and lasting disease control when used earlier in patients who have relapsed.

Can CELMoDS enhance immunotherapy in early disease and late relapse?

CELMoDs, which include the drugs iberdomide and mezigdomide, are oral treatments designed to help the immune system target and attack myeloma cells. CELMoDs work in a similar way as immunomodulatory agents, such as Revlimid® or Pomalyst®, but are designed to be more potent and effective. Oral treatments offer additional benefits in that they are easy to take and are available to anyone regardless of where they live.

One essential quality of CELMoDs is their ability to “rev up” the immune response. At ASH, many studies were focused on how well CELMoDs can enhance existing therapies. Whether combined with early-line therapies like stem cell therapy (ASCT) or later-line therapies like Elrexfio (elranatamab, a bispecific antibody), researchers are exploring whether CELMoDs can be effective across different stages of the disease—helping to deepen responses, achieve no detectable disease, and provide options for long-term treatment.

While CELMoDs are not yet available for routine clinical use, researchers are actively working to better understand their safety and effectiveness for potential future approval.

• For newly diagnosed multiple myeloma patients: A Phase 2 clinical trial in 120 patients tested different doses of iberdomide as maintenance therapy after a stem cell transplant. Iberdomide helped deepen responses in many patients, with about half achieving MRD-negativity, meaning they had no detectable cancer, and over 80% remaining cancer-free after two years. The most common side effect was low white blood cell counts, which sometimes led to infections; serious side effects were uncommon. Now that researchers have identified an effective and tolerable dose, Iberdomide can now be studied in larger trials.
• For patients who have relapsed following one to three prior lines of therapies: In a Phase 2 clinical trial, 30 patients with relapsed or refractory multiple myeloma were treated with a four-drug combination of iberdomide, Kyprolis®, Darzalex® and dexamethasone. All patients had previously received 1-3 prior lines of therapies, including Revlimid®. Ninety-two percent of patients responded to 4-drug combination treatment. Importantly, these patients were able to stay on iberomide alone for long-term treatment, with regular and ongoing MRD monitoring to make sure the disease stayed under control. While some patients had low blood counts, which could increase the risk of infection, it was manageable with medication or dose adjustments.
• For patients who have relapsed following two to four prior treatments: A Phase 1b study tested a combination of elranatamab, a BCMA-targeted bispecific antibody, and oral iberdomide in 22 patients with relapsed/refractory multiple myeloma who had received two to four prior treatments. After about six months, 91% of patients responded to treatment, and 46% had a complete remission or better. Most patients had side effects, usually mild or moderate, including fatigue, low blood counts, and diarrhea. Serious side effects were less common.

Stay tuned for tomorrow’s final dispatch from ASH 2025, where we’ll bring you even more exciting updates on groundbreaking research that is shaping the future of multiple myeloma care.