Dr van de Donk on Initial Safety and Efficacy Findings From the First-In-Human Study of JNJ-5322 in R/R Multiple Myeloma

"These results appear promising, although the follow-up remains short and larger patient cohorts are still needed to confirm these findings.”

Niels van de Donk, MD, a professor of hematology at Amsterdam University Medical Centers, discussed initial safety and efficacy findings from the first-in-human phase 1 study (NCT05652335) of JNJ-5322—a trispecific antibody targeting BCMA, GPRC5D, and CD3—in patients with relapsed or refractory multiple myeloma.

In this trial, JNJ-5322 was administered subcutaneously every 4 weeks at the recommended phase 2 dose (RP2D) of 100 mg, preceded by a single step-up dose of 5 mg. Findings from the study showed that this regimen was associated with a manageable safety profile. Cytokine release syndrome (CRS) was observed in 69.2% of patients who did not receive prophylactic tocilizumab (Actemra), but all events were grade 1 or 2, and the use of prophylactic tocilizumab reduced the CRS rate to 20%. No grade 3 or higher CRS events occurred. Grade 3 or higher infections were reported in 28.6% of patients. Van de Donk emphasized the importance of early intravenous immunoglobulin support when IgG levels fall below 4 g/L.

JNJ-5322–associated GPRC5D toxicities—including dysgeusia, anorexia, and dysphagia—were observed, but these adverse effects were milder, less frequent, and of shorter duration than those typically seen with GPRC5D-targeting bispecific antibodies, such as talquetamab-tgvs (Talvey). Weight loss, a notable concern with talquetamab, was minimal with JNJ-5322.

Among BCMA-directed and GPRC5D-directed therapy–naive patients treated at the RP2D, the overall response rate was 100.0%, with a complete response or better rate of 70.4% and a very good partial response or better rate of 96.3%. At 12 months, the estimated progression-free survival rate in this population was 95.0%. Van de Donk noted that the depth and durability of response with JNJ-5322 were comparable with those observed with CAR T-cell therapies, despite JNJ-5322 being an off-the-shelf, outpatient-administered agent.