Talquetamab May Be Underutilized in Relapsed/Refractory Myeloma

In August 2023, the FDA approved talquetamab (Talvey) for multiple myeloma that had been treated with 4 or more prior lines of therapy.¹ However, in a recent poll of advanced practice providers (APPs) and oncology nurses conducted at a community case forum on bispecific antibodies in myeloma, most responded that they have not yet used the agent in practice.

Specifically, 13.3% of respondents said that they have referred eligible patients to receive the drug, although 86.7% said that they have not used the drug at all.

Event moderator, Lindsey Halbrook, NP-BC, MSN, discussed how talquetamab—a GPRC5D-targeting bispecific antibody—can be used in heavily pretreated patients with myeloma.

“Looking at the [National Comprehensive Cancer Network (NCCN)] Guidelines … for patients that are relapsed/refractory after 4 prior lines of therapy, you can have patients go to CAR T-cell therapy or also to bispecifics,” Halbrook, an advanced practice provider at the Colorado Blood Cancer Institute in Denver, said during the event.

Talquetamab Data from the MonumenTAL-1 Trial

The efficacy of talquetamab was established in the phase 1/2 MonumenTAL-1 clinical trial (NCT04634552), which included patients with heavily pretreated myeloma; 143 received 0.4 m/kg SQ QW, 145 received 0.8 mg/kg SC Q2W, and 51 received either dose.²

Overall survival (OS) and progression-free survival (PFS) data for each of the three groups were:

• The 0.4 mg/kg had a 78.9% 12-month OS rate; median PFS was 7.5 months (95% CI, 5.7-9.4); 12-month PFS rate was 34.9%
• The 0.8 mg/kg group had a 12-month OS rate of 90.5%; mean PFS was 14.2 months (95% CI, 9.6-NE); and 12-month PFS rate of 54.4
• The either dose group had a 12-month OS rate of 80.5%; Median PFS was 5.1 months (95% CI, 3.4-12.3); and 12-month PFS rate was 38.1%

The objective response rates (ORR) were 74.1%, 71.7%, and 64.7% in the 0.4 mg/kg, 0.8 mg/kg, and either dosing groups, respectively.

Adverse Events from Talquetamab

Common non-hematologic adverse events (AEs) from talquetamab were related to taste, skin, or nails. Patients taking the drug also experienced an increased rate of infection and rash.

“You mostly see infections and neutropenia in all three of the cohorts, grade three or four infections is about 20 to 25% of patients, and neutropenia is seen in grade three to four in about a third to half of the patients as well, and a lot of a lot of times the neutropenia does kind of coincide with an infection, although less likely to see neutropenia coincide with Like a grade three or four infection as well,” Halbrook said.

Patients who responded to talquetamab were able to able to undergo dose reductions or be dosed less frequently, according to a cohort of 19 patients in the MonumenTAL-1 trial who underwent a dose or frequency reduction.

“It is important to know that patients did have to be in a response before the dose reduction could occur, and the dose reduction generally occurred at a median of about 3.1 months relative to when the treatment started,” Halbrook explained.

Among the entire dose-reduction cohort, at a median follow-up of 13.2 months, the median PFS was 13.2 months (95% CI, 8.8-NE), whereas the 12-month PFS rate was 50.1 months (95% CI, 27.9-68.7). The median duration of response was not evaluable.

In the subgroup of patients who received 0.8 mg/kg Q2W (n=145), the ORR was 71.7%. The median PFS was 14.2 months (95% CI, 9.6-NE), with a 12-month PFS rate of 54.5%. Similarly, the median duration of response was not evaluable in this group.

“We’re not doing any bispecific at our office currently,” one of the attendees said. “I know that (my institution) is trying to change that, and some other offices are, but I think managing a lot of the toxicities and monitoring all of that is something that they’re trying to figure out.”

References

1. U.S. FDA approves Talvey (talquetamab-tgvs), a first-in-class bispecific therapy for the treatment of patients with heavily pretreated multiple myeloma. News release. Janssen. August 10, 2023. Accessed August 10, 2023. https://www.janssen.com/us-fda-approves-talveytm-talquetamab-tgvs-first-class-bispecific-therapy-treatment-patients-heavily

2. Cjaro A. Minnema MC, Berdeja JG, et. al. Talquetamab, a T-Cell–Redirecting GPRC5D Bispecific Antibody for Multiple Myeloma. N Engl J Med 2022;387:2232-2244. DOI: 10.1056/NEJMoa2204591