Dr Suvannasankha on the Safety/Efficacy of REGN5459 in R/R Multiple Myeloma

Attaya Suvannasankha, MD, Associate Professor of Clinical Medicine, Indiana University School of Medicine, Indiana University Health System, discusses the safety and efficacy of REGN5459, a BCMAxCD3 bispecific antibody with low affinity to CD3 on T cells, in relapsed/refractory multiple myeloma.

At the 2023 AACR Annual Meeting, Suvannasankha presented data from a first-in-human phase 1/2 trial (NCT04083534) of REGN5459 in patients with multiple myeloma who were relapsed/refractory or intolerant to at least 3 prior lines of therapy, including an anti-CD38 monoclonal antibody, an immunomodulatory agent, and a proteasome inhibitor, and who exhausted all treatment options.

Among evaluable patients across all dose levels (n = 43), the objective response rate (ORR) was 65.1%, including a very good partial response (VGPR) or better in 58.1% of patients and a complete response (CR) or better in 51.2% of patients. Within patients treated at higher doses between 480 mg and 900 mg (n = 21), the ORR was 90.5%, including a CR or better rate of 61.9% and a VGPR or better rate of 76.2%. These levels of response in a heavily pretreated and historically difficult-to-treat population were notable, Suvannasankha says, adding that this patient population typically has a tough time achieving a deep remission.

Among patients who had a CR or better who were evaluable for minimal residual disease (MRD; n = 19), 79.0% were MRD negative at the 10-5 threshold. MRD testing allowed investigators to better understand how deep remission was for this subset of patients, Suvannasankha continues.

Data from the phase 1 and 2 portions of the trial showed that REGN5459 had an acceptable safety/tolerability profile. Any-grade treatment-emergent adverse effects (TEAEs) were reported in 100% of patients, and grade 3/4 TEAEs occurred in 74.4% of patients across all dose levels. Any-grade cytokine release syndrome (CRS) occurred in 53.5% of patients; however, the majority of instances of CRS were low grade (grade 1, 46.5%; grade 2, 2.3%). Two patients (4.7%) experienced grade 3 CRS, and no grade 4/5 events were observed. One patient experienced grade 2 immune effector cell–associated neurotoxicity syndrome.

Other common TEAEs included cough, dyspnea, and infection, Suvannasankha notes. Infection occurred 62.8% of patients, and 30.2% of patients had grade 3/4 infection. The most common infections of any grade consisted of urinary tract infection, pneumonia, sinusitis, and upper respiratory infection. Two patients had grade 5 AEs, including 1 patients with pneumonia and 1 with COVID-19, Suvannasankha concludes.