KEY TAKEAWAYS
- The phase 2 study evaluated MRD negativity as a measure of response to ciltacabtagene autoleucel in relapsed/refractory multiple myeloma (RRMM).
- The study utilized next-generation sequencing (NGS) methods to assess MRD negativity.
- The findings underline the importance of MRD negativity as a marker for positive treatment in RRMM patients receiving CAR-T therapy.
In the CARTITUDE-1 study, treating patients (pts) with chimeric antigen receptor-T cell (CAR-T) therapy, specifically ciltacabtagene autoleucel (cilta-cel), led to minimal residual disease (MRD) negativity in 92% of pts with relapsed/refractory multiple myeloma (RRMM). While MRD negativity typically correlates with extended progression-free survival (PFS), the connection between sustained MRD negativity and other measures in CARTITUDE-1 remains unestablished.
The study outlined the methodology used to determine MRD-negativity status in the CARTITUDE-1 and present the treatment outcomes of patients who maintained MRD negativity in CARTITUDE-1.
In the study, 97 pts diagnosed with RRMM, who had previously undergone treatment with at least three different lines of treatment, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody, were administered a single infusion of cilta-cel. MRD negativity was evaluated using next-generation sequencing (NGS) methods. Bone marrow aspirate samples were obtained from pts to identify the presence of gene mutations, known as myeloma clones, and then collected on day 28 and at months 6, 12, 18, and 24 following treatment to assess the frequency of these clones. Calibration and quality-control checks were applied to ensure that the samples contained adequate cells to detect MRD negativity, defined as the presence of fewer than one myeloma cell in every 105 nucleated cells. Patients were classified on the basis of the duration of MRD negativity (<6 months, 6-12 months, ≥12 months). Patients with 2 MRD-negative results ≥ six months (before disease progression or commencement of additional treatment) were deemed to have maintained MRD negativity. The study also involved a comparative analysis of the duration of response (DOR) and PFS between pts with sustained MRD negativity and those without it.
Among 61 pts whose samples met the standards for MRD assessment using NGS after calibration and quality control,92% (56 pts) achieved MRD negativity. The persistence of MRD negativity exhibited was observed: 22 pts sustained it for<6 mos, 10 pts maintained it between 6 and 12 mos, and 24 pts sustained it for ≥ 12 mos. Patients with sustained MRD negativity displayed extended median (with a 95% confidence interval) DOR (6-12 months: NE [12.5 mo, NE]; ≥12 months: NE [NE, NE]) and PFS (6-12 months: NE [13.4 months, NE]; ≥12 months: NE [NE, NE]).In comparison, pts with sustained MRD negativity for less than six months exhibited a DOR of 10.3 mos (5.1, 15.6) and a PFS of 11.0 mos (5.4, 16.6).
MRD negativity was a significant measure of treatment response in the CARTITUDE-1 study, showing a clear connection with positive treatment outcomes. It is crucial for nurse practitioners to comprehend the significance of conducting baseline sampling for MRD evaluations and to recognize the clinical implications that stem from this favorable treatment outcome.
Source: https://ons.confex.com/ons/2023/meetingapp.cgi/Paper/13543
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03548207
Aronson, E., Madduri, D., Suarez, J., Florendo, E., Pacaud, L., Steinbach, M.
