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FDA Grants Talquetamab Accelerated Approval for R/R Multiple Myeloma


Patients with relapsed/refractory multiple myeloma may now receive talquetamab following the agent’s accelerated approval by the FDA.

A version of this article was originally published on CancerNetwork. This version has been lightly edited.

The FDA has granted accelerated approval to talquetamab-tgvs (Talvey) for patients with relapsed/refractory multiple myeloma who have undergone at least 4 previous lines of therapy including a proteosome inhibitor, immunomodulatory agent, and anti-CD38 antibody, according to a press release from The Janssen Pharmaceutical Companies.1

The approval is based on results from the phase 1/2 MonumenTAL-1 trial (NCT03399799; NCT0463452), which assessed talquetamab, a first-in-class, off-the-shelf T-cell redirecting bispecific antibody against the GPRC5D and CD3 receptors. The 0.8 mg/kg subcutaneous dose of the agent resulted in an overall response rate (ORR) of 73.6% (95% CI, 63.0%-82.4%). After a median follow-up of 6 months, the very good partial response rate (VGPR) was 58% and the complete response (CR) rate or better was 33%. Additionally, the corresponding ORR at the subcutaneous 0.4 mg/kg dose was 73.0% (95% CI, 63.2%-81.4%); the VGPR was 57% and the CR or better rate was 35% at a median follow-up of 14 months.

Responses were long lasting, with investigators reporting that the median duration of response was not reached at the 0.8 mg/kg dose level and 9.5 months with 0.4 mg/kg. A total of 85% of patients in the 0.8 mg/kg group continued to respond for a minimum of 9 months.

Eligibility criteria for the phase 1 portion of the study included patients who had progressed on or were intolerant to all available therapies. An ECOG performance status of 0 to 2 was also required. In the study’s second phase, patients needed to have received 3 or more prior therapies, and have an ECOG performance status of 0 to 2.2

Patients were given either talquetamab (n = 143) at 0.4 mg/kg or 0.8 mg/kg (n = 145). Additionally, there was a third cohort (n = 51) of patients—who were able to have previously received previous T-cell redirection therapy—who could receive either dose level.

“The clinically meaningful efficacy and safety profile observed with talquetamab in heavily pretreated patients in this clinical trial, which included patients treated with prior BCMA-targeted bispecific or CAR-T cell therapy, has been notable,” said Ajai Chari, MD, director of Multiple Myeloma Program and a professor of Clinical Medicine at the University of California, San Francisco. “Patients at this stage of the disease have a poor prognosis. Talquetamab as a first-in-class therapy is a new option for patients with this difficult-to-treat blood cancer.”

In a previous publication of the study,2 between the 0.4 mg/kg and 0.8 mg/kg cohorts, the median patient age was 67 years, with 31.1% vs 28.9% having high-risk cytogenetics, respectively. Additionally, 93.0% of patients in the 0.4 mg/kg arm and 92.4% in the 0.8 mg/kg arms were previously exposed to an anti-CD38 monoclonal antibody, with 74.1% vs 69.0% being refractory to 3 classes of drug, respectively.

Investigators reported an objective response rate (ORR) of 74.1% in the 0.4 mg/kg group and the 0.8 mg/kg group of 73.1%. In the 0.4 mg/kg group. A total of 23.8% of patients achieved a stringent complete response (sCR), 9.8% had a CR, 25.9% had a very good partial response (VGPR), and 14.7% had a partial response (PR). Corresponding rates in the 0.8 mg/kg group were 20.0%, 12.4%, 24.8%, and 15.9%. The median duration of response (DOR) had not been reached at the time of the data read out.

Additionally, 70.6% of the population received prior CAR T-cell therapy, 35.3% had a prior bispecific antibody, and 7.8% were belantamab (Blenrep) refractory. Of those who received prior T-cell redirection, the ORR was 62.7%. This included a sCR rate of 17.6%, a CR rate of 5.9%, a VGPR rate of 29.4%, and a PR rate of 9.8%. The median DOR was 12.7 months.

In the 0.4 mg/kg arm, the median progression-free survival was 7.5 months (95% CI, 5.7-9.4), and it was 11.9 months (95% CI, 8.4-not estimable) in the 0.8 mg/kg arm.

The most common hematologic adverse effects (AEs) overall were cytopenia. Regarding grade 3/4 AEs, the most common were anemia (31.5% vs 24.8%), neutropenia (30.8% vs 22.1%), lymphopenia (25.9% vs 25.5%), and thrombocytopenia (20.3% vs 16.6%) in the 0.4 mg/kg and 0.8 mg/kg groups, respectively.

A total of 57.3% of patients in the 0.4 mg/kg group and 50.3% in the 0.8 mg/kg group experienced infections, 16.8% and 11.7% of which were high-grade, respectively. In each respective treatment arm, 13 patients and 16 patients contracted COVID-19, and 2 patients died.

While there was a low rate of discontinuation, the majority of patients discontinued because of cytokine release syndrome (CRS), with most events being grade 1/2. Investigators noted that the incidence of grade 3/4 skin, nail, and rash toxicities was low.

Immune-effector cell-associated neurotoxicity syndrome occurred in 10% of patients in the 0.4 kg/mg group and 11% in the 0.8 mg/kg group, with most events being low-grade.

Additionally, common any-grade AEs in the 0.4 mg/kg arm included CRS (79.0%) and skin AEs (55.9%); grade 3/4 AEs included fatigue (3.5%) and pyrexia (2.8%). In the 0.8 kg/mg group, any-grade AEs were CRS (72.4%), skin AEs (67.6%), and dysgeusia (46.2%), and grade 3/4 AEs were rash (5.5%) and dysphagia (2.1%).


1. U.S. FDA approved TALVEY (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. The Janssen Pharmaceuticals. August 10, 2023. Accessed August 10, 2023. https://prn.to/3KwnjyD

2. Chari A, Touzeau C, Schinke C, et al. Talquetamab, a G protein-coupled receptor family C group 5 member D x CD3 bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM): phase 1/2 results from MonumenTAL-1. Blood. 2022; 140(suppl 1):384-387. doi.10.1182/blood-2022-159707

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