KEY TAKEAWAYS
- The MonumenTAL-1 phase 1 trial aimed to investigate the efficacy and safety of talquetamab dosing modifications in patients with R/R MM.
- Researchers noticed that talquetamab dosing adjustments maintain efficacy in managing AE’s without compromising treatment outcomes.
Talquetamab is the first approved T-cell redirecting bispecific antibody targeting the novel antigen, G protein-coupled receptor class C group 5 member D (GPRC5D), on myeloma cells. Data from the MonumenTAL-1 trial in patients with relapsed/refractory multiple myeloma (RRMM) showed overall response rates (ORRs) of >71%. GPRC5D-related adverse events (AEs), including dysgeusia and skin/nail toxicities, are novel off-tumor, on-target AEs that have been managed with supportive care or dose modifications.
In the MonumenTAL-1 trial, an analysis showed that patients who switched to reduced or less frequent dosing after achieving partial response or better (≥PR) or to mitigate treatment-emergent AEs (TEAEs) maintained their responses.
Patricia Blazquez and the team aimed to investigate the efficacy and safety of talquetamab dosing modifications in patients with RRMM while maintaining treatment responses.
They performed an inclusive analysis of the MonumenTAL-1 study, which included 2 prospective dose modification cohorts: (1) reduced dose cohort (talquetamab 0.8 mg/kg biweekly [Q2W] switched to 0.4 mg/kg Q2W), and (2) less frequent dosing cohort (talquetamab 0.8 mg/kg Q2W switched to 0.8 mg/kg monthly), resulting in reduced dose intensity for both cohorts. Switching required a ≥PR.
In prospective dose modification cohorts (n=24; median follow-up, 13.2 months), 19 patients switched to reduced intensity dosing after achieving ≥PR (reduced dose, n=9; less frequent dosing, n=10). Dosing modification occurred at a median of 3.1 months (range, 2.3–4.2) after treatment started.
The ORR was 79.2% (19/24), with 75% of patients achieving ≥VGPR, and the median DOR was not reached. Estimated median PFS was 13.2 months (8.8–NE). Although AEs typically began within 90 days (prior to switch), fewer new-onset GPRC5D-related AEs occurred following the switch. There was a trend toward more improved and resolved GPRC5D-related AEs in dosing-modified patients compared with patients who did not reduce dose.
The study concluded that responses in patients receiving reduced or less frequent dosing of talquetamab were comparable to those in the MonumenTAL-1 trial (ORR, 71.7% at 0.8 mg/kg Q2W; median PFS, 14.2 months). Oncology nurses, pivotal in talquetamab administration, TEAE monitoring, and patient education, can advise patients that while a high proportion respond positively to talquetamab, those experiencing GPRC5D-related adverse events often show an initial response within 90 days. Importantly, dose modifications did not compromise efficacy, highlighting the potential for early management of treatment-related adverse events through dose reduction without impacting treatment response.
The study concluded that pembrolizumab exhibited a notable occurrence of AE’s, predominantly falling within mild to severe grades (grade 1-3), with fatigue being frequently reported. Despite this, the AE’s were generally manageable and did not necessitate hospitalization or treatment discontinuation.
The trial was sponsored by the Janssen Research & Development, LLC.
Source: https://ons.confex.com/ons/2024/meetingapp.cgi/Paper/15540
Clinical Trial: https://clinicaltrials.gov/study/NCT03399799
Blazquez P, Chari A, Renaud T, et al. (2024). “Nursing Considerations for Talquetamab Dosing in Patients With Relapsed/Refractory Multiple Myeloma.” Presented at ONS 2024 (Abstract I23).
