New Trispecific Antibody JNJ-5322 Shows Strong Results in Relapsed/Refractory Myeloma

Can the new trispecific antibody JNJ-5322 offer a safe and effective option for people with relapsed or refractory multiple myeloma?

Early study results of JNJ-5322 reveal how this next-generation therapy targets myeloma, its response rates, safety profile, and how it may shape future treatment options. 

How the myeloma trispecific antibody works 

JNJ-5322 (JNJ-79635322, Johnson & Johnson) is a next-generation trispecific antibody. It builds on the previous experience of bispecific antibodies teclistamab and talquetamab by simultaneously attaching to three different proteins: BCMA and GPRC5D on myeloma cells and CD3 on T-cells. 

This “double lock-down” effect on myeloma cells may help overcome treatment resistance and attack more diverse cancer cells. This could be especially useful for people whose myeloma has stopped responding to other therapies, such as relapsed/refractory patients. 

Who was included in the phase 1 study?

The phase 1 trial included 126 people with relapsed/refractory myeloma. All had previously been treated with a proteasome inhibitor, an immunomodulatory medicine, and an anti-CD38 monoclonal antibody, with 56% of patients being resistant to these. About one-third had high-risk myeloma genetics, and nearly one in four had previously received BCMA or GPRC5D-directed therapies.

This group represents people with advanced and challenging-to-treat myeloma, making the study results especially meaningful.

Promising response rates, especially in certain groups

Among the 36 people who received the recommended phase 2 dose (100 mg every 4 weeks after a 5 mg step-up dose), 86.1% responded to JNJ-5322. Even more promising, 100% of patients who had never been treated with BCMA or GPRC5D-targeted therapies responded, with 96.3% achieving a very good partial response or better. For these patients, the 12-month progression-free survival rate was 95%. 

The response rates are important because they are similar to those seen with CAR T-cell therapy. However, JNJ-5322 is a ready-to-use (off-the-shelf) treatment. It can be given in outpatient settings, potentially avoiding the complex preparation and hospitalization that comes with CAR-T.

Dr. Niels van de Donk from VU University Medical Center led the study, with results presented at the 2025 ASCO and EHA conferences. 

Understanding the safety profile of JNJ-5322

Like most therapies, side effects were reported with JNJ-5322. If you have questions about how side effects are managed, please speak with your myeloma specialist. 

One of the most common was cytokine release syndrome (CRS), which occurred in 59% of participants. However, all cases were mild to moderate, and no one experienced severe CRS. Using a step-up dosing strategy likely helped reduce this risk.

Other common effects included changes in taste (58%), nail issues (55%), non-rash skin changes (50%), and low neutrophils, a type of white blood cell (49%). Infections were reported in 75% of patients, with 28% being more serious (grade 3 or 4). Click here to learn about supportive measures used against infections during treatment. 

Knowing about these possible side effects can help you and your care team weigh the benefits and risks when choosing a myeloma therapy.

Why this trispecific antibody could change future myeloma treatment

The study’s findings suggest JNJ-5322 may offer a new outpatient option for people with hard-to-treat multiple myeloma. Its ability to bind to two targets on myeloma cells could reduce the chance of the cancer escaping treatment. Also, its monthly dosing may provide a more manageable schedule for patients and care partners.

Importantly, its strong results in people who had not received other BCMA or GPRC5D therapies show that earlier use in treatment may be especially beneficial.

If you're interested in JNJ-5322 as a therapy option, click here to check your eligibility for the study. You can also use the button below to explore other clinical trials in HealthTree Cure Hub®, which are matched to you based on your medical history.

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Sources: 

• ASCO | First-in-human study of JNJ-79635322 (JNJ-5322), a novel, next-generation trispecific antibody (TsAb), in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Initial phase 1 results
• Early results from Johnson & Johnson’s trispecific antibody show promising response in heavily pretreated multiple myeloma patients
• EHA | FIRST-IN-HUMAN STUDY OF JNJ-79635322 (JNJ-5322), A NOVEL, NEXT-GENERATION TRISPECIFIC ANTIBODY, IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA: INITIAL PHASE 1 RESULTS