Contributions
Abstract: EP964
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) is a chimeric antigen receptor T (CAR-T) cell therapy with two B-cell maturation antigen–targeting single-domain antibodies. CARTITUDE-1 (NCT03548207) is a phase 1b/2 study conducted to evaluate cilta-cel in patients with relapsed/refractory multiple myeloma (R/R MM).
Aims
We report updated CARTITUDE-1 results in patients with a longer duration (median 12.4 months) of follow-up.
Methods
All patients provided informed consent. Eligible patients had MM, had received ≥3 prior regimens or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), and had received a PI, IMiD, and anti-CD38 antibody. Bridging therapy was permitted after apheresis. Patients received a single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg; range 0.5–1.0×106) 5–7 days after lymphodepletion with 300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for 3 days. The primary objectives of the study were to characterize the safety of cilta-cel, confirm the recommended phase 2 dose (RP2D; phase 1b), and evaluate efficacy (phase 2). Cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by Common Terminology Criteria for Adverse Events (CTCAE), v5.0 (in phase 1b). CRS and immune effector cell‐associated neurotoxicity syndrome (ICANS) were graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria (in phase 2). In this analysis, Lee et al and CTCAE v5.0 were mapped to ASTCT for CRS and ICANS, respectively.
Results
As of Sept 1, 2020, a total of 97 patients with a median of 6 prior lines of therapy received cilta‑cel. The overall response rate per independent review committee (primary endpoint) was 97% (95% CI, 91–99), with 67% of patients achieving stringent complete response. The median time to first response was 1 month (range, 1–9), and median time to complete response or better was 2 months (range, 1–15). Responses deepened over time, and the median duration of response was not reached. Of 57 patients who were evaluable for minimal residual disease (MRD) assessment, 93% were MRD-negative at 10-5. The 12-month progression-free survival (PFS) and overall survival rates were 77% (95% CI, 66–84) and 89% (95% CI, 80–94), respectively; the median PFS was not reached. Grade 3/4 hematologic adverse events (AEs) that occurred in ≥20% of patients included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred in 95% of patients (4% were grade 3/4), with median time to onset of 7 days (range, 1–12) and median duration of 4 days (range, 1–14, excluding 1 patient with duration of 97 days). CRS resolved in all patients except one with grade 5 CRS/haemophagocytic lymphohistiocytosis. CAR-T cell neurotoxicity occurred in 21% of patients (10% were grade ≥3). A total of 14 patients died during the study after cilta-cel infusion: no deaths occurred within the first 30 days, 2 deaths occurred within 100 days; and 12 deaths occurred more than 100 days post infusion, of which 5 were from disease progression, and 4 from treatment-related AEs.
Conclusion
A single infusion of cilta-cel yielded early, deep, and durable responses in heavily pretreated patients with MM, with a manageable safety profile at the RP2D. Investigation of cilta‑cel in other MM populations in earlier lines of therapy and in outpatient settings is under investigation.
Keyword(s): B-cell maturation antigen, CAR-T, Multiple myeloma
Abstract: EP964
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Ciltacabtagene autoleucel (cilta-cel; JNJ-68284528) is a chimeric antigen receptor T (CAR-T) cell therapy with two B-cell maturation antigen–targeting single-domain antibodies. CARTITUDE-1 (NCT03548207) is a phase 1b/2 study conducted to evaluate cilta-cel in patients with relapsed/refractory multiple myeloma (R/R MM).
Aims
We report updated CARTITUDE-1 results in patients with a longer duration (median 12.4 months) of follow-up.
Methods
All patients provided informed consent. Eligible patients had MM, had received ≥3 prior regimens or were double refractory to a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), and had received a PI, IMiD, and anti-CD38 antibody. Bridging therapy was permitted after apheresis. Patients received a single cilta-cel infusion (target dose: 0.75×106 CAR+ viable T cells/kg; range 0.5–1.0×106) 5–7 days after lymphodepletion with 300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for 3 days. The primary objectives of the study were to characterize the safety of cilta-cel, confirm the recommended phase 2 dose (RP2D; phase 1b), and evaluate efficacy (phase 2). Cytokine release syndrome (CRS) was graded by Lee et al (Blood 2014) and neurotoxicity by Common Terminology Criteria for Adverse Events (CTCAE), v5.0 (in phase 1b). CRS and immune effector cell‐associated neurotoxicity syndrome (ICANS) were graded by American Society for Transplantation and Cellular Therapy (ASTCT) criteria (in phase 2). In this analysis, Lee et al and CTCAE v5.0 were mapped to ASTCT for CRS and ICANS, respectively.
Results
As of Sept 1, 2020, a total of 97 patients with a median of 6 prior lines of therapy received cilta‑cel. The overall response rate per independent review committee (primary endpoint) was 97% (95% CI, 91–99), with 67% of patients achieving stringent complete response. The median time to first response was 1 month (range, 1–9), and median time to complete response or better was 2 months (range, 1–15). Responses deepened over time, and the median duration of response was not reached. Of 57 patients who were evaluable for minimal residual disease (MRD) assessment, 93% were MRD-negative at 10-5. The 12-month progression-free survival (PFS) and overall survival rates were 77% (95% CI, 66–84) and 89% (95% CI, 80–94), respectively; the median PFS was not reached. Grade 3/4 hematologic adverse events (AEs) that occurred in ≥20% of patients included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred in 95% of patients (4% were grade 3/4), with median time to onset of 7 days (range, 1–12) and median duration of 4 days (range, 1–14, excluding 1 patient with duration of 97 days). CRS resolved in all patients except one with grade 5 CRS/haemophagocytic lymphohistiocytosis. CAR-T cell neurotoxicity occurred in 21% of patients (10% were grade ≥3). A total of 14 patients died during the study after cilta-cel infusion: no deaths occurred within the first 30 days, 2 deaths occurred within 100 days; and 12 deaths occurred more than 100 days post infusion, of which 5 were from disease progression, and 4 from treatment-related AEs.
Conclusion
A single infusion of cilta-cel yielded early, deep, and durable responses in heavily pretreated patients with MM, with a manageable safety profile at the RP2D. Investigation of cilta‑cel in other MM populations in earlier lines of therapy and in outpatient settings is under investigation.
Keyword(s): B-cell maturation antigen, CAR-T, Multiple myeloma