The phase 1b/2 CARTIRUDE-1 study found deep and durable responses, along with a tolerable safety profile with the recommended phase 2 dose of ciltacabtagene autoleucel for patients with relapsed or refractory multiple myeloma.
Early, deep, and durable responses and a manageable safety profile were observed with a single infusion of ciltacabtagene autoleucel (JNJ-68284528; cilta-cel) at the recommended phase 2 dose for heavily pretreated patients with relapsed/refractory multiple myeloma, according to results from the phase 1b/2 CARTITUDE-1 study (NCT03548207) published in The Lancet.
Patients who received cilta-cel at the recommended phase 2 dose of 0.75×106 CAR-positive viable T cells per kg, the overall response rate (ORR) was 97% (95% CI, 91.2%-99.4%), with 67% of patients achieving a stringent complete response (CR) at a median follow-up of 12.4 months (interquartile range [IQR], 10.6-15.2). The median time to first response was 1.0 months (IQR 0.9-1.0).
“This analysis of the phase 1b/2 CARTITUDE-1 study establishes a positive risk–benefit profile for a single low-dose infusion of cilta-cel, yielding early, deep, and durable responses in heavily pretreated patients with multiple myeloma,” the investigators wrote. “Cilta-cel is under further investigation in other populations of patients with multiple myeloma in earlier line settings.”
Trial eligibility required patients to be aged 18 years or older with multiple myeloma as characterized by the International Myeloma Working Group (IMWG) diagnostic criteria. Patients also needed measurable disease at screening and an ECOG performance status of 0 or 1. Additionally, 3 or more prior lines of therapy and documented disease progression at 12 months or less following last line of therapy were required for enrollment.
The primary end points of the phase 1b portion of the study were safety and confirming the recommended phase 2 dose. ORR was the primary end point of the phase 2 portion. Phase 1b and 2 of this study occurred sequentially.
Lymphodepletion was undertaken with 300 mg/m2 of cyclophosphamide and 30 mg/m2 of fludarabine intravenously daily for 3 days. Five to 7 days after lymphodepletion, cilta-cel was given at the recommended dose of 0.75 × 106 CAR-positive viable T cells per kg.
A total of 113 patients enrolled on the study and underwent apheresis from July 16, 2018 to October 7, 2019, 97 of whom received the cilta-cel infusion. The median patient age was 61 years (IQR, 56.0-68.0) and 59% of patients were male. Seventy-five percent of patients received bridging therapy between apheresis and cilta-cel infusion.
Additional findings from the trial demonstrated a median time to best response of 2.6 months and a median time to complete response or better of 1.9 months. A total of 62% patients who achieved a CR or better responsed within 3.0 months of undergoing infusion. The median duration of response was not reached in this analysis (95% CI, 15.9–not estimable [NE]).
The median progression-free survival (PFS) was not met (95% CI, 16.8-NE) and the overall 12-month PFS rate was 77% (95% CI, 66.0%-84.3%). The 12-month PFS rates for patients achieving a CR or better and for those achieving a very good partial response (PR) or PR were 85% (95% CI, 72.0%-91.8%) and 62% (95% CI, 42.1%-76.9%), respectively. Additionally, the overall survival (OS) rate at 12 months was 89% (95% CI, 80.2%-93.5%).
Adverse effects (AEs) were reported in all 97 patients who underwent cilta-cel infusion. Common grade 3/4 hematological AEs included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Fifty-eight percent of patients experienced infections, 20% of which were grade 3/4 with common infections including pneumonia (8%) and sepsis (4%).
“Cilta-cel might be a viable treatment option for patients with relapsed or refractory multiple myeloma, with the highest overall response rate achieved to date in this heavily pretreated population who received a previous proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody, including those who are triple-class refractory or penta-drug refractory,” the investigators wrote.
Berdeja JG, Madduri D, Usmani SZ, et al. Ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in patients with relapsed or refractory multiple myeloma (CARTITUDE-1): a phase 1b/2 open-label study. Lancet. 2021;398(10297):314-324. doi:10.1016/S0140-6736(21)00933-8