KEY TAKEAWAYS
- The CARTITUDE-1 phase 1b/2 trial aimed to provide clinical response data and analyze correlative biomarkers in R/R MM pts.
- Researchers noticed a significantly extended PFS with a single infusion of cilta-cel, surpassing outcomes seen with previously approved therapies for heavily pretreated R/R MM.
Ciltacabtagene autoleucel (cilta-cel), an FDA-approved chimeric antigen receptor (CAR)-T cell (T) therapy, has shown efficacy in relapsed/refractory multiple myeloma (R/R MM) after ≥4 lines of therapy (LOT).
Yi Lin and her team aimed to consolidate clinical response findings from the Phase 1b/2 CARTITUDE-1 trial at study closeout, along with correlative biomarker analyses.
Researchers performed an inclusive analysis including patients (pts) eligible for the study who had received ≥3 prior LOTs or were double refractory to proteasome inhibitor (PI) and immunomodulatory (IMiD) drugs. All participants had a history of prior PI, IMiD, and anti-CD38 antibody therapy.
The primary endpoint focused on evaluating the overall response rate (ORR) and safety, while secondary endpoints included progression-free survival (PFS), overall survival (OS), duration of response (DOR), and minimal residual disease (MRD) negativity at 10-5. In-depth assessments of patient (PT) and CAR-T drug product (DP) characteristics were conducted to identify biomarkers associated with the response to cilta-cel.
About 97 pts were included in the study, with a median follow-up of 33.4 months (range, 1.5-45.2). The response rate reached 97.9%, and the median DOR was 33.9 months (95% CI, 25.5-not estimable [NE]). Median PFS stood at 34.9 months (95% CI, 25.2-NE), with an estimated PFS rate of 47.5% at 36 months. Median OS was not reached (NR), showing an estimated OS rate of 62.9% at 36 months.
Among the 49 pts evaluated for MRD, 26 sustained MRD negativity for ≥12 months. Within this subgroup, 20 pts achieved sustained MRD-negative complete response or greater, and their median PFS was NR. No new safety signals were reported. The CAR-T DP comprised a mix of transduced (median [range], 16% [5%-32%]) and nontransduced T cells, with a balanced distribution of CD4+ (median [range] frequency, 12% [2%-28%]) and CD8+ CAR+T cells (6% [2%-20%]). The median peak expansion of CAR+ T cells occurred at 730 cells/µL between 12 and 14 days post-infusion, persisting in a median (range) of 100 (20-912) days.
Despite variable CAR-T cell expansion and lack of detectable CAR-T cell persistence over time, deep and durable responses (eg, best response and DOR) were achieved. Some DP characteristics, including a high CAR+CD8+ stem-like phenotype and a low CAR+CD4+ Treg-like phenotype, were associated with longer DOR. Patient characteristics linked to baseline inflammatory markers correlated with shorter DOR. Patients with high-risk cytogenetics, tumor burden ≥60% bone marrow plasma cells, or baseline plasmacytomas demonstrated a high ORR but numerically shorter PFS.
The study concluded that a single infusion of cilta-cel yielded a prolonged PFS compared to previously reported therapies for heavily pretreated R/R MM. Correlative analyses suggest the potential for identifying DP, pt, and tumor characteristics to enhance the prediction of DOR to cilta-cel.
The study is sponsored by Janssen Research & Development, LLC
Source: https://tandem.confex.com/tandem/2024/meetingapp.cgi/Paper/23283
Clinical Trial: https://clinicaltrials.gov/study/NCT03548207
Lin Y, Usmani S. Z, Berdeja J G, et al. (2024). “Biomarker Correlates of 3 Year Response in Cartitude-1: A Phase 1b/2 Open-Label Study of Ciltacabtagene Autoleucel in Patients with Relapsed or Refractory Multiple Myeloma.” Presented at TCT-ASTCT-CIBMTR 2024, Abstract (515).
