Outcomes in patients with MM achieving MRD negativity after treatment with cilta-cel: CARTITUDE-1

Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen-directed autologous chimeric antigen receptor T-cell therapy, is approved by the U.S. Food and Drug Administration for treatment of patients with relapsed/refractory multiple myeloma (R/R MM) after ≥4 lines of therapy.¹ The Multiple Myeloma Hub has previously reported various updates on CARTITUDE-1 trial (NCT03548207). Previous findings from CARTITUDE-1 have demonstrated deep and durable responses with cilta-cel, with 56 of 61 evaluable patients in phase Ib/2 achieving minimal residual disease (MRD) negativity.¹

During the 11^th Annual Meeting of the Society of Hematologic Oncology (SOHO) 2023, Yi Lin presented the latest updates from CARTITUDE 1 trial, focusing on efficacy outcomes and characteristics of patients with R/R MM and sustained MRD negativity following treatment with cilta-cel. We are pleased to summarize the key updates here.

Study design¹

The study design and interim data have been reported previously on the Multiple Myeloma Hub. For this analysis, patients achieving sustained MRD negativity were defined as those with:

• Two MRD-negative results following cilta-cel infusion, and
• No MRD-positive results prior to progression or subsequent therapy, which were ≥6 months apart.

MRD negativity was assessed at baseline, on Day 28, and 6, 12, 18, and 24 months after cilta-cel infusion as a key secondary endpoint of the phase II part of the CARTITUDE-1. An additional sample was assessed at the time of suspected complete response and every 12 months until progressive disease.

Results

Disease and patient characteristics in MRD subgroups

A total of 56 patients achieving MRD negativity were included in the analysis. Baseline characteristics were comparable between patients with sustained ≥6 months versus <6 months MRD negativity (Table 1). However, patients with sustained MRD negativity for ≥12 months showed a tendency towards longer time since diagnosis.

Table 1. Disease and patient baseline characteristics*

Response rates

Stringent complete response was achieved by all patients with sustained MRD negativity ≥6 months. Comparison of response rates in patients with >6 months versus ≥6 months MRD negativity are shown in Figure 1.

• Median duration of response was longer in patients with sustained versus <6 months MRD negativity (not evaluable vs 10.3 months).
• Similarly, progression-free survival was increased in patients with sustained versus <6 months MRD negativity (not evaluable vs 11 months).

Figure 1. Response rates in MRD subgroups* 

MRD, minimal residual disease; ORR, overall response rate; PR, partial response; sCR, stringent complete response; VGPR, very good partial response.
*Data from Lin.^1
†ORR = sCR + VGPR + PR.

Conclusion

This analysis from CARTITUDE-1 demonstrated that achievement of sustained MRD negativity was not predicted by baseline patient and disease characteristics. However, patients achieving sustained MRD negativity for ≥12 months showed a tendency towards longer time since diagnosis. Deeper responses were achieved in patients who achieved MRD negativity for ≥6 months versus <6 months. In addition, patients with MRD negativity for ≥6 months showed longer duration of response and progression-free survival compared with those achieving <6 months MRD negativity.