|The following article features coverage from the 2021 Annual Meeting of the Society of Hematologic Oncology (SOHO). Click here to read more of Hematology Advisor‘s conference coverage.|
A single dose of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) cell therapy, yielded early, deep, and durable responses in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM).
The findings were presented by Saad Usmani, MD, of Levine Cancer Institute-Atrium Health, Charlotte, NC, at the Annual Meeting of the Society of Hematologic Oncology (SOHO).
CARTITUDE-1 (ClinicalTrials.gov Identifier: NCT03548207) is an on-going phase 1b/2 study. The primary objectives are characterization of cilta-cel safety, including cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome, and confirmation of the recommended phase 2 dose and evaluation of efficacy. Dr Usmani presented updated results with a longer duration of follow-up (median 18 months) for the study.
Patients enrolled in the study had RRMM with measurable disease who had received ≥3 prior regimens (or double refractory to proteasome inhibitor and immunomodulatory drug) and anti-CD38. They received a single cilta-cel infusion, with a targeted dose of 0.75×106 (0.5-1.0×106) CAR+ viable T cells/kg, following lymphodepletion with cyclophosphamide/fludarabine. The median administered dose was 0.71×106 (0.51-0.95×106) CAR+ viable T cells/kg.
A total of 97 patients, with a median age of 61 years (range, 43-78 years; 58.8% male and 17.5% Black), who had a median of 6 prior lines of therapy (range, 3-18), received cilta-cel. Most (87.6%) patients were triple-class refractory and 42.3% were penta-drug refractory. All patients except 1 (99%) were refractory to their last line of therapy.
At a median follow up of 18-months, overall response rate was 97.9%, including 80.4% with stringent complete response (sCR), 14.4% with very good partial response, and 3.1% with partial response. The median time to first response was 1 month (range, 0.9–10.7 months). The median time to ≥CR was 2.6 months (range, 0.9–15.2 months). The median duration of response was 21.8 months (95% CI, 21.8-Non-estimable [NE]) and for patients with sCR had not been reached. Of 61 patients who were evaluable for minimal residual disease (MRD), 91.8% were MRD-negative at 10–5 (patients with ≥CR: 89.4%).
The 18-month progression-free survival (PFS) and overall survival rates were 66% (95% CI, 54.9-75.0) and 80.9% (95% CI, 71.4-87.6), respectively. The median PFS was 22.8 months (95% CI, 22.8-NE) and was not reached for those with sCR.
No new safety signals were detected with longer follow up. Grade 3/4 hematologic adverse events (AEs) included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred in 95% of patients (95% grade 1/2), resolving within 14 days of onset in most cases (99%); median time to onset of 7 days (range, 1-12 days). CAR-T cell neurotoxicity occurred in 21% patients, with 10% grade ≥3.
The investigators also reported the successful implementation of new patient management strategies to prevent and reduce the incidence of neurotoxicity.
“At a longer follow up of 18 months, a single dose of cilta-cel led to early, deep, and durable responses in heavily pretreated patients with multiple myeloma,” concluded Dr Usmani. “Cilta-cel is showing a safety profile that is consistent with its mechanism of action, without any new safety signals.”
Disclosure: This research was supported by Janssen Research & Development, LLC and Legend Biotech, Inc. Please see the original reference for a full list of disclosures.
Read more of Hematology Advisor’s coverage of SOHO 2021 by visiting the conference page.
Usmani SZ, Berdeja JG, Madduri D, et al. Updated results of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T (CAR-T) cell therapy in relapsed/refractory multiple myeloma (RRMM). Paper presented at: Annual Meeting of the Society of Hematologic Oncology (SOHO); September 8-11, 2021. Abstract MM-119.