Contributions
Abstract: EP1003
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Ciltacabtagene autoleucel (Cilta-cel or JNJ-68284528) is a chimeric antigen receptor T (CAR-T) cell therapy with two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer high avidity binding. In the phase 2, multicohort, open-label CARTITUDE-2 (NCT04133636) study, the efficacy and safety of cilta-cel in patients with multiple myeloma (MM) were assessed in various clinical settings.
Aims
To describe the mitigation and management strategies implemented in order to identify and reduce the risk for neurologic adverse events (AEs) in Cohort A patients (progressive MM after 1−3 prior lines of therapy).
Methods
Eligible patients (≥18 years of age) had MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, progressive MM after 1−3 prior lines of therapy (including a proteasome inhibitor and immunomodulatory drug), and were lenalidomide refractory (no prior BCMA-targeting agent). All patients provided informed consent prior to enrollment in the study. Patients received cilta-cel (0.75×106 [range: 0.5–1.0×106] CAR+ viable T cells/kg) as a single infusion 5–7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). Monitoring and mitigation strategies for neurologic AEs included providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T-related immune effector cell-associated neurotoxicity syndrome (ICANS) using the immune effector cell-associated encephalopathy tool, regular handwriting assessments to detect micrographia, and neuroimaging (brain MRI) and EEG for patients with prior neurologic disease. Management strategies included evaluation of infectious and paraneoplastic etiologies upon observation of ICANS ≥ grade 1, administration of tocilizumab (if concurrent cytokine release syndrome [CRS], all grade of ICANS) and/or dexamethasone (grade 2/3) or methylprednisolone (grade 4). ICANS and CRS were graded by American Society for Transplantation and Cellular Therapy criteria; neurotoxicities not classified as ICANS were graded per Common Terminology Criteria for Adverse Events version 5.0.
Results
As of 15 Jan 2021 (median follow-up: 5.8 months [range: 2.5–9.8 months]), 20 patients in Cohort A received cilta-cel. The median age was 60 years (range: 38–75) and 65% of patients were male. Neurotoxicities occurred in 4 patients (20%). Three patients had ICANS (grade 1/2); the median time to onset of symptoms was 8 days (range: 7–11), and the median duration was 2 days (range: 1–2). Two of the 3 patients received supportive measures to treat ICANS, including levetiracetam and steroids; all 3 had concurrent CRS and all recovered. One patient developed isolated grade 2 facial paralysis on Day 29 after cilta-cel infusion and recovered 51 days after the onset of event following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported.
Conclusion
Neurologic AEs were generally manageable in patients with MM following treatment with cilta-cel. With a median follow-up of 5.8 months, there were no movement or neurocognitive disorders in patients with progressive MM who had received 1−3 prior lines of therapy (Cohort A). These results suggest that early detection and management of neurologic AEs can lead to better treatment outcomes.
Keyword(s): B-cell maturation antigen, CAR-T, Multiple myeloma, Safety
Abstract: EP1003
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
Ciltacabtagene autoleucel (Cilta-cel or JNJ-68284528) is a chimeric antigen receptor T (CAR-T) cell therapy with two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer high avidity binding. In the phase 2, multicohort, open-label CARTITUDE-2 (NCT04133636) study, the efficacy and safety of cilta-cel in patients with multiple myeloma (MM) were assessed in various clinical settings.
Aims
To describe the mitigation and management strategies implemented in order to identify and reduce the risk for neurologic adverse events (AEs) in Cohort A patients (progressive MM after 1−3 prior lines of therapy).
Methods
Eligible patients (≥18 years of age) had MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, progressive MM after 1−3 prior lines of therapy (including a proteasome inhibitor and immunomodulatory drug), and were lenalidomide refractory (no prior BCMA-targeting agent). All patients provided informed consent prior to enrollment in the study. Patients received cilta-cel (0.75×106 [range: 0.5–1.0×106] CAR+ viable T cells/kg) as a single infusion 5–7 days after start of lymphodepletion (cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 daily for 3 days). Monitoring and mitigation strategies for neurologic AEs included providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T-related immune effector cell-associated neurotoxicity syndrome (ICANS) using the immune effector cell-associated encephalopathy tool, regular handwriting assessments to detect micrographia, and neuroimaging (brain MRI) and EEG for patients with prior neurologic disease. Management strategies included evaluation of infectious and paraneoplastic etiologies upon observation of ICANS ≥ grade 1, administration of tocilizumab (if concurrent cytokine release syndrome [CRS], all grade of ICANS) and/or dexamethasone (grade 2/3) or methylprednisolone (grade 4). ICANS and CRS were graded by American Society for Transplantation and Cellular Therapy criteria; neurotoxicities not classified as ICANS were graded per Common Terminology Criteria for Adverse Events version 5.0.
Results
As of 15 Jan 2021 (median follow-up: 5.8 months [range: 2.5–9.8 months]), 20 patients in Cohort A received cilta-cel. The median age was 60 years (range: 38–75) and 65% of patients were male. Neurotoxicities occurred in 4 patients (20%). Three patients had ICANS (grade 1/2); the median time to onset of symptoms was 8 days (range: 7–11), and the median duration was 2 days (range: 1–2). Two of the 3 patients received supportive measures to treat ICANS, including levetiracetam and steroids; all 3 had concurrent CRS and all recovered. One patient developed isolated grade 2 facial paralysis on Day 29 after cilta-cel infusion and recovered 51 days after the onset of event following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported.
Conclusion
Neurologic AEs were generally manageable in patients with MM following treatment with cilta-cel. With a median follow-up of 5.8 months, there were no movement or neurocognitive disorders in patients with progressive MM who had received 1−3 prior lines of therapy (Cohort A). These results suggest that early detection and management of neurologic AEs can lead to better treatment outcomes.
Keyword(s): B-cell maturation antigen, CAR-T, Multiple myeloma, Safety