MMRF at ASCO 2025: Day 2 – What Patients Should Know

Welcome back to our coverage of the 2025 ASCO Annual Meeting. On Day 2, researchers shared more promising updates about long-term results from large, ongoing clinical trials, new treatment combinations, and patient-friendly innovations in multiple myeloma care.

CAR T-Cell Therapy: Patients Cancer-Free After 5 Years

Long-term data were presented from the CARTITUDE-1 study of the CAR-T cell therapy Carvykti^® (cilta-cel) in 97 heavily pretreated patients with relapsed or refractory myeloma.

• Five years after a single infusion of Carvykti, about 1 in 3 patients were still off treatment, living cancer-free.
• Close to 36% of these cancer-free patients were initially diagnosed with high-risk disease, including chromosomal alterations and myeloma tumors in different parts of the body (extramedullary disease).
• Researchers are looking beyond genetics to figure out what has helped stall disease progression for 5 years in these patients, including their T-cell makeup.

The MMRF’s new Translational Research Umbrella (TRU) Program asks similar questions to help us understand which patients respond to specific therapies and why. Combined efforts like CARTITUDE-1 and TRU will be key in understanding the long-term benefit of Carvykti and who can benefit the most.

Above all, these are some of the most positive results we’ve seen as a treatment for heavily pre-treated.

Strength with Newer Treatment Combinations

Yesterday, we highlighted how adding Darzalex^® (daratumumab) to standard three-drug treatment helps patients who aren’t getting a transplant. Today, we heard similar long-term success in another group of patients who did receive a transplant.

• In the PERSEUS trial, newly diagnosed, transplant-eligible patients received Darzalex plus Velcade^®(bortezomib), Revlimid^® (lenalidomide), and dexamethasone (DVRd).
• These patients were more likely to reach and stay in MRD-negative status (no detectable cancer) for up to two years compared to those on Velcade, Revlimid, and dexamethasone alone.
• 95% of patients who stayed MRD-negative had a high chance of being cancer-free at four years.

We also saw more good news for Sarclisa^® (isatuximab). A study of newly diagnosed patients found that adding Sarclisa to Kyprolis^® (carfilzomib), Revlimid, and dexamethasone (Isa-KRd) led to:

• Greater percentage of high-risk patients with 2 or more chromosomal alterations reaching MRD-negativity compared to those on the triplet regimen (KRd) (62% vs 20%).
• Better long-term remission after one year (52% vs. 38%)
• No increase in side effects compared to the three drug combination

Given the improvement in outcomes and no significant side effects or impact on quality of life, this study and others from yesterday confirm that four-drug combinations are the standard of care treatment across different newly diagnosed patient populations.

From Bispecifics to Trispecifics

Day 2 also offered an exciting glimpse into potential new treatments on the horizon, including JNJ-5322, a new trispecific antibody that targets two regions of myeloma cells instead of one. This new therapy could be a particularly effective treatment for patients who have just relapsed after taking a proteasome inhibitor like Velcade, an immunomodulatory drug like Revlimid, or an anti-CD38 antibody like Sarclisa.

• 100% of relapsed/refractory patients in a phase I trial responded to the drug if they had not taken any other bispecific or CAR T-cell therapies.
• Side effects were similar to those seen in other bispecific antibody treatments and included cytokine release syndrome (CRS), infections, decrease in white blood cells, and taste loss.

Now that this Phase I trial discovered an optimal dose that minimizes side effects, we look forward to watching JNJ-5322 as it moves to the next stages of testing—Phase 2 and Phase 3 trials—where more patients can access the drug.

A New Way of Giving Sarclisa Offers New Possibilities for Patient Care

Today’s last study looked at a new way to give the medicine Sarclisa using a small, wearable device called an on-body delivery injector (OBI). This device sticks to the belly and uses a tiny needle to deliver the medicine. The goal of the study was to see if this new method works just as well as the current way of giving Sarclisa, which is through an IV drip.

• Both methods worked equally well, with 71% of patients responding in both groups. Side effects were also similar between the two groups.
• The study also found that patients wearing the injector had far fewer injection related reactions and reported higher satisfaction with the treatment than patients who received an IV infusion.
• Delivery of Sarclisa took only 20 minutes using the OBI.

The wearable injector may be used in the future to improve quality of life by making treatment more comfortable, convenient, and less disruptive to daily activities. One day, it could possibly be administered in a patient’s own home instead of a treatment center.

Moving forward, it will be important to figure out what can be done to minimize cost of this new device and increase everyone’s access to it.

We’re excited by the continued momentum in myeloma research that we’ve seen at ASCO 2025. For more updates, visit themmrf.org and follow along as we track the progress that brings us closer to a cure.