Legend Biotech Corporation presented new and updated results from the CARTITUDE clinical development program studying ciltacabtagene autoleucel (cilta-cel) in the treatment of multiple myeloma at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting. Earlier data from the CARTITUDE-1 study supported recent regulatory approvals for CARVYKTI™ by the U.S. Food and Drug Administration and the European Commission, and ongoing results from the multi-cohort CARTITUDE-2 study are being used to inform future trials of CARVYKTI™ treatment in multiple patient populations and treatment settings. Data from the ongoing Phase 1b/2 CARTITUDE-1 study continue to show deep and durable responses in heavily pretreated patients with relapsed or refractory multiple myeloma at a median 28-month follow up (MFU), with an overall response rate (ORR) of 98% (95% Confident Interval [CI], 92.7-99.7).

Responses in 97 patients treated with CARVYKTI™ were sustained from the 22-month median follow-up data previously presented at the 2021 American Society of Hematology (ASH) Annual Meeting, with 83% of patients achieving a stringent complete response (sCR) at median 28 MFU.1 Median progression-free survival (PFS) and median overall survival (OS) were not reached at time of follow-up, suggesting long-term durability of responses and survival for patients. Two-year PFS and OS rates were 55% (95% CI, 44.0–64.6) and 70% (95% CI, 60.1–78.6), respectively. Sixty-one patients had samples evaluable for minimal residual disease (MRD) status, and of those, 92% achieved MRD negativity at the 10-5 threshold.1 Of those evaluable, MRD negativity was sustained for more than 6 months in 68% and more than 12 months in 55% of patients.1 Two year PFS rates in patients who achieved sustained MRD negativity for 6 months or longer and 12 months or longer were 73% (95% CI, 52.1 to 85.9) and 79% (95% CI, 51.5 to 91.8), respectively.

In these same patients, two-year OS rates were 94% (95% CI, 76.1 to 98.3) and 91% (95% CI, 67.7 to 97.6), respectively. The CARTITUDE-1 study included patients who received a median of six prior treatment regimens (range, 3-18). All patients were triple-class [immunomodulatory agent (IMiD), proteasome inhibitor (PI) and anti-CD38 antibody] exposed, while 42% of patients were penta-drug refractory and 99% of patients were refractory to the last line of therapy.

Median time to first response was one month (range, 0.9-10.7 months), with responses deepening over time.1 Additionally, median time to best response was 2.6 months (range, 0.9-17.8 months) and median time to complete response (CR) or better was 2.9 months (range, 0.9-17.8 months). At 28-month median follow up, the most common hematologic adverse events (AEs) observed were neutropenia (96%); anemia (81%); thrombocytopenia (79%); leukopenia (62%); and lymphopenia (54%). Since the primary 12-month publication, no new events of CRS (no changes in incidence, time to onset, or duration) occurred and one new case of Parkinsonism (also referred to as movement and neurocognitive treatment-emergent adverse events) occurred.

Results from the multicohort Phase 2 CARTITUDE-2 study (NCT04133636) evaluating cilta-cel safety and efficacy in various clinical settings for patients with multiple myeloma were also presented at ASCO 2022, demonstrating the promise of CARVYKTI™ earlier in the course of multiple myeloma treatment. Updated data from Cohort A examined the safety and efficacy of cilta-cel in 20 patients with multiple myeloma after one to three prior lines of therapy and who are lenalidomide-refractory (Abstract #8020). At a median follow-up of 17.1 months, the ORR was 95%, which included 90% of patients achieving CR or better and 95% achieving very good partial response (VGPR) or better.

The median time to first response was one month and the median time to best response was 2.6 months. The 15-month PFS rate was 70%. Of the 16 patients who were MRD-evaluable, all achieved MRD negativity at 10-5.4 Results from Cohort B of the study, evaluating the safety and efficacy of cilta-cel in patients relapsed or refractory multiple myeloma who received one prior line of therapy including a PI and IMiD and had disease progression within 12 months of treatment with autologous stem cell transplant (ASCT) or within 12 months of the start of antimyeloma therapy for patients who have not had ASCT, were also presented (Abstract #8029).

At a median of 13 months follow-up, 19 patients treated in this cohort achieved an ORR of 100%, with 90% of patients achieving a CR or better, and 95% of patients achieving a VGPR or better. Median time to first response was one month (range, 0.9-9.7) and median time to best response was 5.1 months.5 The 12-month PFS rate was 90%. Of the 15 patients who were MRD-evaluable, 14 achieved MRD negativity at 10-5.