KEY TAKEAWAYS
- The CARTITUDE-1 phase I/II trials aimed to define long-term efficacy, PFS, and associated disease features in patients achieving sustained undetectable MRD.
- The results demonstrated that Cilta-cel was effective across diverse patients, but deeper remissions and lasting success may rely on specific disease and patient features, calling for personalized optimization strategies.
For a study, researchers aimed to define long-term efficacy, progression-free survival(PFS), and associated disease features in patients achieving sustained undetectable minimum residual rate (MRD).
The study included relapsed and refractory multiple myeloma (RRMM) patients undergoing at least three prior treatments, including a proteasome inhibitor, immunomodulatory drug, and anti-CD38 monoclonal antibody.
Bone marrow samples were collected at various time points: baseline, day 28, months 6, 12, 18, and 24 post-treatment. Next-generation sequencing was employed to assess MRD negativity.
Patients were categorized based on MRD negativity duration (<6 months, 6-12 months, ≥12 months), and sustained MRD negativity was defined as having two MRD-negative results at least 6 months apart, occurring before disease progression or subsequent treatment.
The intervention involved a single infusion of cilta-cel. The primary outcome measures included PFS, and comparisons were made between patients with and without sustained MRD negativity.
Among the 56 evaluable patients who achieved MRD negativity, 50 and 44 demonstrated follow-up durations of ≥6 and ≥12 months without progression after the initial MRD negativity, respectively. Sustained MRD negativity was observed for <6 months in 22 patients, 6-12 months in 10 patients, and ≥12 months in 24 patients.
Patients with sustained MRD negativity for 6-12 months and ≥12 months exhibited longer PFS (6-12 months: not evaluable [NE] [13.4 months, NE]; ≥12 months: NE [NE, NE]) compared to those with <6 months’ sustained MRD negativity (PFS: 11.0 months [5.4, 16.6]).
Patients with sustained MRD negativity for ≥6 months and ≥12 months were less likely to have baseline extramedullary plasmacytomas (8.8%, n=3/34 and 4.2%, 1/24, respectively) than patients with <6 months’ sustained MRD negativity (18.2%, 4/22) and showed a trend toward a longer median time since diagnosis (5.9 years and 7.0 years, respectively) compared to patients with sustained MRD negativity <6 months (4.8 years). Other baseline characteristics did not differ across MRD subgroups.
The results demonstrated the broad efficacy, deeper disease remissions, and sustained long-term outcomes may hinge on specific disease and patient factors, warranting further studies for personalized treatment optimization.
Source: https://clml-soho2023.elsevierdigitaledition.com/486/index.html
Clinical Trial: https://clinicaltrials.gov/study/NCT03548207
Munshi, N., Pavia, B., Martin, T., et al. (2023). “Efficacy Outcomes and Characteristics of Patients With Multiple Myeloma (MM) Who Achieved Sustained Minimal Residual Disease Negativity After Treatment With Ciltacabtagene Autoleucel (cilta‑cel) in CARTITUDE‑1.” Presented at the SOHO 2023. (Abstract MM-304)
