INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2
Objective: Cilta-cel (JNJ-68284528) is a chimeric antigen receptor T cell (CAR-T) therapy with two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer high avidity binding. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort, open-label study assessing the efficac...
| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2021-10-01
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| Series: | Hematology, Transfusion and Cell Therapy |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2531137921005940 |
| _version_ | 1830431492523687936 |
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| author | H Einsele S Parekh D Madduri B Santomasso JG Pérez-Larraya NWV Donk B Arnulf M Mateos KC Braganca H Varsos MJ Carrasco-Alfonso M Akram N Lendvai CC Jackson Y Olyslager E Zudaire C Li D Geng A Jakubowiak A Cohen |
| author_facet | H Einsele S Parekh D Madduri B Santomasso JG Pérez-Larraya NWV Donk B Arnulf M Mateos KC Braganca H Varsos MJ Carrasco-Alfonso M Akram N Lendvai CC Jackson Y Olyslager E Zudaire C Li D Geng A Jakubowiak A Cohen |
| author_sort | H Einsele |
| collection | DOAJ |
| description | Objective: Cilta-cel (JNJ-68284528) is a chimeric antigen receptor T cell (CAR-T) therapy with two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer high avidity binding. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort, open-label study assessing the efficacy and safety of cilta-cel in patients with multiple myeloma (MM) in various clinical settings. We describe the mitigation and management strategies implemented to identify and reduce the risk for neurologic adverse events in patients enrolled in Cohort A (progressive MM after 1-3 prior lines of therapy). Method and materials: Eligible patients (≥18 years of age) had MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, progressive disease after 1-3 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory drug), were lenalidomide refractory, and had not received BCMA-targeting agents. Cilta-cel (0.75 × 106 [range 0.5– 1.0 × 106] CAR+ viable T cells/kg) was given 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 adverse events include providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T related immune effector cellassociated neurotoxicity syndrome (ICANS) using the immune effector cellassociated encephalopathy tool, regular handwriting assessments to detect micrographia, and neuroimaging (brain MRI) and electroencephalogram for patients with prior neurologic disease. Management strategies include evaluating infectious and paraneoplastic etiologies upon observation of ICANS ≥grade 1, administration of tocilizumab (if concurrent with 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, v5.0. Results: As of 15 Jan 2021 (median follow-up: 5.8 months [range: 2.5–9.8]), 20 patients in Cohort A received cilta-cel. Median age was 60 years (range: 38–75) and 65% were male. Neurotoxicities occurred in 4 patients (20%). Three patients had ICANS (grade 1/2); median time to onset of symptoms was 8 days (range: 7–11) and 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 facial paralysis (grade 2) on Day 29 after cilta-cel infusion and recovered 51 days after onset following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported. Discussion: Early detection and management of neurologic adverse events can lead to better treatment outcomes. Conclusion: Neurologic adverse events were generally manageable in patients with MM following treatment with cilta-cel. With a median of 5.8 months of follow-up, there were no movement or neurocognitive disorders in patients from Cohort A. |
| first_indexed | 2024-12-21T02:08:46Z |
| format | Article |
| id | doaj.art-970c727b96e8414794c118943459ebf6 |
| institution | Directory Open Access Journal |
| issn | 2531-1379 |
| language | English |
| last_indexed | 2024-12-21T02:08:46Z |
| publishDate | 2021-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Hematology, Transfusion and Cell Therapy |
| spelling | doaj.art-970c727b96e8414794c118943459ebf62022-12-21T19:19:26ZengElsevierHematology, Transfusion and Cell Therapy2531-13792021-10-0143S263S264INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2H Einsele0S Parekh1D Madduri2B Santomasso3JG Pérez-Larraya4NWV Donk5B Arnulf6M Mateos7KC Braganca8H Varsos9MJ Carrasco-Alfonso10M Akram11N Lendvai12CC Jackson13Y Olyslager14E Zudaire15C Li16D Geng17A Jakubowiak18A Cohen19Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, GermanyMount Sinai Medical Center, New York, United StatesMount Sinai Medical Center, New York, United StatesMemorial Sloan Kettering Cancer Center, New York, United StatesClínica Universidad de Navarra, Pamplona, SpainDepartment of Hematology, Cancer Center Amsterdam, Amsterdam UMC, Vrije Universiteit Amsterdam, Amsterdam, NetherlandsSaint-Louis University Hospital AP-HP, Paris, FranceInstitute of Cancer Molecular and Cellular Biology, University Hospital of Salamanca, Salamanca, SpainJanssen R&D, Raritan, New Jersey, United StatesJanssen R&D, Raritan, New Jersey, United StatesLegend Biotech USA, Inc., Piscataway, United StatesLegend Biotech USA, Inc., Piscataway, United StatesJanssen R&D, Raritan, New Jersey, United StatesJanssen R&D, Raritan, New Jersey, United StatesJanssen R&D, Beerse, BelgiumJanssen R&D, Spring House, United StatesJanssen R&D, Spring House, United StatesLegend Biotech USA, Inc., Piscataway, United StatesUniversity of Chicago, Chicago, United StatesAbramson Cancer Center, University of Pennsylvania, Philadelphia, United StatesObjective: Cilta-cel (JNJ-68284528) is a chimeric antigen receptor T cell (CAR-T) therapy with two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies designed to confer high avidity binding. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort, open-label study assessing the efficacy and safety of cilta-cel in patients with multiple myeloma (MM) in various clinical settings. We describe the mitigation and management strategies implemented to identify and reduce the risk for neurologic adverse events in patients enrolled in Cohort A (progressive MM after 1-3 prior lines of therapy). Method and materials: Eligible patients (≥18 years of age) had MM per International Myeloma Working Group criteria, measurable disease, Eastern Cooperative Oncology Group performance status ≤1, progressive disease after 1-3 prior lines of therapy (including a proteasome inhibitor and an immunomodulatory drug), were lenalidomide refractory, and had not received BCMA-targeting agents. Cilta-cel (0.75 × 106 [range 0.5– 1.0 × 106] CAR+ viable T cells/kg) was given 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 adverse events include providing more effective bridging therapy to reduce tumor burden prior to lymphodepletion, frequent assessment of CAR-T related immune effector cellassociated neurotoxicity syndrome (ICANS) using the immune effector cellassociated encephalopathy tool, regular handwriting assessments to detect micrographia, and neuroimaging (brain MRI) and electroencephalogram for patients with prior neurologic disease. Management strategies include evaluating infectious and paraneoplastic etiologies upon observation of ICANS ≥grade 1, administration of tocilizumab (if concurrent with 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, v5.0. Results: As of 15 Jan 2021 (median follow-up: 5.8 months [range: 2.5–9.8]), 20 patients in Cohort A received cilta-cel. Median age was 60 years (range: 38–75) and 65% were male. Neurotoxicities occurred in 4 patients (20%). Three patients had ICANS (grade 1/2); median time to onset of symptoms was 8 days (range: 7–11) and 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 facial paralysis (grade 2) on Day 29 after cilta-cel infusion and recovered 51 days after onset following treatment with dexamethasone for 28 days. No movement or neurocognitive disorders were reported. Discussion: Early detection and management of neurologic adverse events can lead to better treatment outcomes. Conclusion: Neurologic adverse events were generally manageable in patients with MM following treatment with cilta-cel. With a median of 5.8 months of follow-up, there were no movement or neurocognitive disorders in patients from Cohort A.http://www.sciencedirect.com/science/article/pii/S2531137921005940 |
| spellingShingle | H Einsele S Parekh D Madduri B Santomasso JG Pérez-Larraya NWV Donk B Arnulf M Mateos KC Braganca H Varsos MJ Carrasco-Alfonso M Akram N Lendvai CC Jackson Y Olyslager E Zudaire C Li D Geng A Jakubowiak A Cohen INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2 Hematology, Transfusion and Cell Therapy |
| title | INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2 |
| title_full | INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2 |
| title_fullStr | INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2 |
| title_full_unstemmed | INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2 |
| title_short | INCIDENCE, MITIGATION, AND MANAGEMENT OF NEUROLOGIC ADVERSE EVENTS IN PATIENTS WITH MULTIPLE MYELOMA TREATED WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) IN CARTITUDE-2 |
| title_sort | incidence mitigation and management of neurologic adverse events in patients with multiple myeloma treated with ciltacabtagene autoleucel cilta cel in cartitude 2 |
| url | http://www.sciencedirect.com/science/article/pii/S2531137921005940 |
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