FDA Grants Breakthrough Therapy Designation to Talquetamab for Relapsed/Refractory Multiple Myeloma

Patients with relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy might benefit from treatment with talquetamab, which was granted breakthrough therapy designation by the FDA.

Talquetamab was granted breakthrough therapy designation by the FDA for the treatment of patients with relapsed/refractory multiple myeloma who were treated with a minimum of 4 previous lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, according to a press release from Janssen.1

The designation is supported by findings from the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT04634552), which assessed the agent in patients with relapsed/refractory disease.2 Data from the study, which were presented at the 2022 American Society of Clinical Oncology Annual Meeting, indicated that patients who were treated with 405 μg/kg of talquetamab (n = 30) experienced an overall response rate (ORR) of 70.0%, including a very good partial response (VGPR) rate or better of 56.7%. Additionally, the ORR among patients treated at the 800 μg/kg dose was 63.6%, including a VGPR or better of 56.8%. Moreover, the stringent complete response (CR) rates were 23.3% and 9.1%, CR rates were 6.7% and 11.4%, the VGPR rates were 26.7% and 36.4%, and PR rates were 13.3% and 6.8% in each respective arm.

Additional findings from the study indicated that patients in the 405 μg/kg dose group had a median follow up of 13.2 months compared with 7.7 months in the 800 μg/kg group. Across both groups, triple-class–refractory patients had an ORR of 65.2% and 67.6%, respectively. Additionally, patients in the 405 μg/kg and 800 μg/kg groups who were penta-drug–refractory had ORRs of 83.3% and 75.0%, respectively. The median time to first confirmed response was 0.9 months and 1.2 months in each respective cohort.

“Despite the therapies available for patients with relapsed or refractory multiple myeloma, new targets and treatments are needed because of the heterogeneity of the disease, which can impact a patient’s response to treatment. We are resolute in our commitment to advance science and develop new therapies and regimens for patients with the goal of delivering the best possible outcomes while driving toward cures,” Sen Zhuang, MD, PhD, vice president of Clinical Research and Development at Janssen Research & Development, LLC, said in a press release.

Talquetamab is an off-the-shelf T-cell–redirecting bispecific antibody that targets GPRC5D on myeloma cells and CD3 on T cells.

Patients who enrolled on the trial received 1 of 2 subcutaneous dosing schedules: 405 μg/kg weekly per 21-day cycle or 800 μg/kg twice weekly per 28-day cycle. Those in the 405 μg/kg arm had a median age of 61.5 years, 63.3% were men, and 83.3% were White. All patients on this arm were triple-class and 80% were penta-drug exposed, and 76.7% and 20.0%, respectively, were triple-class and penta-drug refractory. In the 800 μg/kg cohort, the average age was 64.0 years, 47.7% of patients were men, and 79.5% were White. In total, 97.7% of patients were triple-class and 68.2% were penta-drug exposed. Additionally, 77.3% and 27.3% of patients were triple class and penta drug refractory.

Common adverse effects (AEs) included cytokine release syndrome (CRS), skin-related events, and dysgeusia. The most common hematologic grade 3/4 AEs in the 405 μg/kg and 800 μg/kg groups, respectively, were neutropenia (60.0% and 34.1%), anemia (30.0% and 27.3%), and lymphopenia (40.0% and 40.9%). Common grade 3/4 AEs in both respective arms included rash-related AEs (3.3% and 15.9%), alanine aminotransferase increase (3.3% and 6.8%), and decreased appetite (3.3% and 2.3%).


  1. Janssen announces U.S. FDA breakthrough therapy designation granted for talquetamab for the treatment of relapsed or refractory multiple myeloma. News release. June 29, 2022. Accessed June 30, 2022. https://bit.ly/3yz6KfX
  2. Minnema MC, Krishnan AY, Berdeja JG, et al. Efficacy and safety of talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): Updated results from MonumenTAL-1. J Clin Oncol. 2022;40(suppl 16):8015. doi:10.1200/JCO.2022.40.16_suppl.8015