Cilta-Cel Demonstrates Durable Responses at 18 Months in Relapsed/Refractory Multiple Myeloma
Darlene Dobkowski, MA
Ciltacabtagene autoleucel, an investigational BCMA-directed CAR-T therapy, sustained efficacy and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma.
Ciltacabtagene autoleucel (cilta-cel), an investigational B-cell maturation antigen (BCMA)-directed CAR-T therapy, sustained efficacy and durable responses in heavily pretreated patients with relapsed/refractory multiple myeloma, according to updated findings of the phase 1b/2 CARTITUDE-1 trial (NCT03548207) slated to be presented during the 2021 ASCO Annual Meeting.1,2
Janssen, the developer of cilta-cel, released the data ahead of an oral presentation scheduled for Tuesday, June 8, 2021.
In new data from the phase 1b/2 CARTITUDE-1 study, cilta-cel induced an overall response rate (ORR) of 97.9% with an 80.4% rate of stringent complete response (sCR), at a median follow-up of 18 months (range, 1.5-30.5). The rate of sCR was 67% in findings presented at the 2020 ASH Annual Meeting, demonstrating a deepening response over time.3
These data include results from 97 patients (median age, 61 years; 58.8% men) who received a median of 6 prior treatment regimens (range, 3-18). All patients had been exposed to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody; 42.3% were penta-drug refractory, and 99% were refractory to their most recent line of therapy. All received a single infusion of cilta-cel (target dose: 0.75×106 CAR+ viable T cells/kg) 5 to 7 days following lymphodepletion.
“The efficacy results observed in heavily pretreated patients with multiple myeloma receiving cilta-cel are remarkable,” principal investigator Saad Z. Usmani, MD, said in a news release. He is Division Chief of Plasma Cell Disorders at Levine Cancer Institute, Atrium Health. “With the possibility of achieving the progression-free-survival reported and responses deepening as observed in the longer-term follow-up, I’m hopeful that cilta-cel will be part of the armamentarium in the future for patients in need of an additional treatment option.”
At 18 months, 66% of patients were alive and progression free (95% CI, 54.9-75.0) with an sCR of 75.9% (95% CI, 63.6-84.5). The rate of overall survival at 18 months was 80.9% (95% CI, 71.4-87.6). Investigators found that response rates were comparable across prespecified subgroups and lines of treatment (range, 95%-100%).
The rate of very good partial response was 14%. Three percent of patients had a partial response (PR). Median time to first response was 1 month (range, 0.9–10.7 months), and the median time to best response was 2.6 months (range, 0.9-15.2 months).Investigators found the results deepened over time, with a median duration of response of 21.8 months (95% CI, 21.8-NE). An estimated 73% of patients who responded to treatment have not progressed or died at 12 months. The median duration of response was not reached in patients with sCR.
Sixty-one patients were evaluable for minimal residual disease (MRD). Of those, 91.8% achieved MRD negativity status at 10-5 at a median of 1 month (range, 0.8-7.7 months) following infusion.
Investigators did not observe any new safety signals with the longer follow-up. The most common any-grade hematologic adverse events (AEs) were neutropenia (95.9%), anemia (81.4%), thrombocytopenia (79.4%), leukopenia (61.9%); and lymphopenia (52.6%).Most patients (n = 92) experienced any-grade cytokine release syndrome (CRS). The median duration of CRS was 4 days (range, 1-97) and 99% resolved within 14 days of onset. Most (95%) were grade 1/2 events.
“Cilta-cel has a manageable safety profile consistent with its mechanism of action,” Usmani said during the presentation.
Janssen filed a marketing authorization application to the European Medicines Agency in April 2021 based on these findings. Additionally, in May 2021, the FDA granted a priority review designation to a biologics license application for cilta-cel in this indication, based on data from CARTITUDE-1. The regulatory agency is expected to make a decision on the application by November 29, 2021, under the Prescription Drug User Fee Act.
Results from cohort A (n = 20) of the phase 2 CARTITUDE-2 study (NCT04133636) of patients with multiple myeloma who progressed following 1 to 3 prior lines of therapy and who were refractory to lenalidomide (Revlimid)
At the February 21 data cutoff, the ORR was 95% with 45% patients achieving a sCR and 30% with a CR. Ten percent of patients had a VGPR and 10% had a PR. The overall safety profile, including incidence of CRS and most common hematologic AEs, was consistent previous results.
References
- Usmani SZ, Berdeja JG, Madduri D, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell (CAR-T) therapy, in relapsed/refractory multiple myeloma (R/R MM): Updated results from CARTITUDE-1. J Clin Oncol. 2021,39(suppl 15; abstr 8005). doi:10.1200/JCO.2021.39.15_suppl.8005
- Janssen reports new data for BCMA CAR-T, cilta-cel, showing deep and durable responses in patients with relapsed or refractory multiple myeloma. News release. Janssen. June 1, 2021. Accessed June 2, 2021. bwnews.pr/3vLIDGW
- Madduri D, Berdeja JG, Usmani SZ, et al. Cartitude-1: phase 1b/2 study of ciltacabtagene autoleucel, a b-cell maturation antigen–directed chimeric antigen receptor t cell therapy, in relapsed/refractory multiple myeloma. Blood. 2020;136(suppl 1):22-25. doi:10.1182/blood-2020-136307
- Agha ME, Cohen AD, Madduri D, et al. CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy. J Clin Oncol. 2021,39(suppl 15; abstr 8013). doi:10.1200/JCO.2021.39.15_suppl.8013
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