Saad Usmani, FACP, MBA, MD from the Department of Hematologic Oncology and Blood Disorders, Atrium Health’s Levine Cancer Institute speaks about the ASCO 2021 Abstract – 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.
Link to Abstract:
https://meetings.asco.org/abstracts-presentations/195437
Background information:
CARTITUDE-1 (NCT03548207) is a phase 1b/2 trial in patients with R/R MM testing ciltacabtagene autoleucel (cilta-cel; JNJ-68284528), a CAR T-cell treatment with two BCMA–targeting single-domain antibodies. We present new findings in pts for a longer follow-up period (median 12.4 months).
Methodologies:
Patients with MM who had undergone three previous regimens or who were double refractory to a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and had received a PI, IMiD, and anti-CD38 antibody were qualified. Bridging therapy was allowed after apheresis. Pts obtained a single cilta-cel infusion 5–7 days (d) after lymphodepletion (300 mg/m2 cyclophosphamide, 30 mg/m2 fludarabine daily for 3 days) (target dose: 0.75106 CAR+ viable T cells/kg; range 0.5-1.0106). The study’s main goals were to determine the safety of cilta-cel, validate the prescribed phase 2 dosage (RP2D; phase 1b), and assess efficacy (phase 2). Lee et al (Blood 2014) graded cytokine release syndrome (CRS) and CTCAE, v5.0, graded neurotoxicity (in phase 1b). The ASTCT standards is used to rate CRS and ICANS (in phase 2). For CRS and ICANS, Lee et al and CTCAE v5.0 were mapped to ASTCT, respectively.
The below are the outcomes:
As of September 1, 2020, 97 points had earned cilta-cel, with a median of six prior lines. The overall response rate per independent review committee (primary endpoint) was 97 percent (95 percent confidence interval, 91–99), with 67 percent achieving strict full response (sCR). The median time to first answer was one month (range: one to nine months), and the median time to CR or best was two months (range: one to fifteen months). The depth of the responses deepened over time, and the median response period was not met. At 10-5, 93 percent of the 57 patients who were evaluable for minimal residual disease (MRD) were MRD-negative. The 12-month progression-free survival (PFS) and total survival (95 percent CI) rates were 77 percent (66–84) and 89 percent (80–94), respectively, with no median PFS. Neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (60%) were among the grade 3/4 hematologic AEs that occurred in 20% of patients (50 percent ). CRS struck 95 percent of patients (4 percent grade 3/4), with a median onset period of 7 days (range 1–12) and a median length of 4 days (range 1–14, except one patient with a 97-day duration). All except one of the patients with grade 5 CRS/haemophagocytic lymphohistiocytosis saw their CRS resolve. CAR T-cell neurotoxicity was observed in 21% of patients (grade 3, 10%). Fourteen people died after receiving cilta-cel infusions during the study: none within the first 30 days, two during the first 100 days, and 12 more than 100 days, with five deaths attributed to disease progression and four leading to treatment-related adverse events.
Final Thoughts:
In heavily pretreated pts with MM, a single infusion of cilta-cel generated early, deep, and durable responses, with a manageable safety profile at the RP2D. Cilta-cel is being studied in other MM communities as a first-line treatment and in outpatient environments. NCT03548207 is the number for the clinical trial.