In an analysis presented at the 2022 ASCO Annual Meeting (Abstract 8028) and simultaneously reported in the Journal of Clinical Oncology, Thomas Martin, MD, and colleagues provided data from the 2-year follow-up of the pivotal CARTITUDE-1 trial of the anti–B-cell maturation agent (BCMA) chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel in relapsed or refractory multiple myeloma.
Thomas Martin, MD
Study Details
Eligible patients had received three or more prior lines of therapy or were double-refractory to a proteasome inhibitor and immunomodulatory drug and had received a prior proteasome inhibitor, immunomodulatory drug, and anti-CD38 therapy. A total of 113 patients were enrolled and underwent apheresis and 111 underwent lymphodepletion; of these, 97 patients received a single dose of ciltacabtagene autoleucel in the target range of 0.5 to 1.0 x 106 CAR T cells/kg (median = 0.71 x 106 cells/kg). Treated patients had received a median of six (range = 3–18) prior lines of therapy. The current analysis occurred 2 years after treatment of the last treated patient enrolled.
Key Findings
Over a median follow-up of 27.7 months in 97 treated patients, the overall response rate was 97.9% (95% confidence interval [CI] = 92.7%–99.7%), including stringent complete response in 82.5% (95% CI = 73.4%–89.4%). No complete responses other then stringent complete response were observed; rates were 12.4% for very good partial response and 3.1% for partial response. Responses deepened over follow-up; for example, the stringent complete response rate improved from 67% at the primary publication at median follow-up of 12 months to 82.5% in the current analysis. Median duration of response was not estimable (95% confidence interval [CI] = 23.3 months–not estimable).
Overall response rates were high across subgroups examined (95.1%–100%), including patients receiving three prior lines of therapy (100%) and those with high-risk cytogenetics (100%), high tumor burden (≥ 60% bone marrow plasma cells; 95.2%), or plasmacytomas (100%).
Median durations of response were shorter among patients with high-risk cytogenetics (22.2 months), International Staging System (ISS) stage III disease (23.1 months), high tumor burden (23.1 months in those with ≥ 60% bone marrow plasma cells), or plasmacytomas (12.9 months).
Median progression-free survival was not reached (95% CI = 24.5 months–not estimable), with 27-month rates of 54.9% (95% CI = 44.0%–64.6%) among all patients and 64.2% (95% CI = 51.9%–74.1%) among those with stringent complete response. Median overall survival was not reached, with a 27-month rate of 70.4% (95% CI = 60.1%–78.6%). Patients with ISS stage III disease, high-risk cytogenetics, high tumor burden, and plasmacytomas had lower progression-free and overall survival rates.
Since the primary publication at a median follow-up of 12 months, no new cases of cytokine-release syndrome were observed. One new case of parkinsonism was reported at day 914 after infusion (bringing the total to six cases observed among treated patients).
The investigators concluded, “At approximately 28 months median follow-up, patients treated with ciltacabtagene autoleucel maintained deep and durable responses, observed in both standard and high-risk subgroups. The risk/benefit profile of ciltacabtagene autoleucel remained favorable with longer follow-up.”
Sundar Jagannath, MD, of Mount Sinai Medical Center, New York, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by Janssen Research & Development, LLC, and Legend Biotech, Inc. For full disclosures of the study authors, visit ascopubs.org.
