Fatal Infection Rates Low with GPRC5D x CD3 Targeting Talquetamab

Infection rates seen with talquetamab appeared lower than with other BCMA-targeting T cell-based therapies for multiple myeloma (MM), according to data from the MonumenTAL-1 study presented at the 2023 American Society of Clinical Oncology Annual Meeting.

Paula Rodríguez-Otero, MD, of Clínica Universidad de Navarra in Pamplona, Spain, and colleagues presented an analysis of infections and parameters of humoral immunity in patients with relapsed or refractory MM treated with talquetamab as part of the MonumenTAL-1 trial.

In the trial, patients received talquetamab at 0.4 mg/kg weekly or 0.8 mg/kg every two weeks. For this analysis, the researchers analyzed data from 339 patients, of whom 51 had prior T-cell redirection therapy (TCRT).

Infections of any grade occurred in 58% of patients in the weekly cohort, 64.8% in the biweekly cohort, and 70.6% of patients with prior TCRT. New-onset infections were most prevalent during the first two cycles of therapy.

Grade 3 or 4 infections occurred in about 20% of patients: 21.7% of patients in the weekly cohort, 15.9% in the biweekly cohort, and 25.5% in patients with prior TCRT. Grade 3 or 4 infections observed in more than two patients assigned to the weekly dosage were pneumonia (3.5%) and urinary tract infection (2.1%); for the biweekly dosage, pneumonia (2.1%) and COVID-19 (2.1%); and for those with prior TCRT, pneumonia (5.9%).

Overall, there were low rates of opportunistic infections; these were observed in 3.5%, 4.1%, and 5.9% of patients in the weekly, biweekly, and prior TCRT cohorts.

There were low rates of discontinuation (1.4%, 0%, and 2.0%) and death (2.1%, 1.4%, and 0%) due to infections in the weekly, biweekly, and prior TCRT cohorts, respectively. Less than 1.5% of patients died from infections, including two patients from COVID-19 pneumonia and one each from septic shock, fungal sepsis, and unknown etiology.

Hypogammaglobulinemia rates by immunglobulin G (IgG) values were 64.3% for the weekly cohort, 65.5% for the biweekly cohort, and 70.6% for patients with prior TCRT. Intravenous immune globulin use was 14.7%, 12.4%, and 15.7%, respectively. The researchers noted that “a trend toward increased nonclonal IgG suggests potential recovery of humoral immunity accompanies rapid, deep, and durable responses to talquetamab.”

Reference

Rodriguez-Otero P, Schinke CD, Chari A,et al. Analysis of infections and parameters of humoral immunity in patients (pts) with relapsed/refractory multiple myeloma (RRMM) treated with talquetamab (tal) monotherapy in MonumenTAL-1. Abstract #8020. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.