Clinical Lymphoma, Myeloma & Leukemia, Vol.21, Suppl.1 - September 2021

Abstracts Clinical Lymphoma, Myeloma & Leukemia September 2021 S422 Amsterdam, Amsterdam, Netherlands, 6 Saint-Louis University Hospital AP-HP, Paris, France, 7 Institute of Cancer Molecular and Cellular Biology, University Hospital of Salamanca, Salamanca, Spain, 8 Janssen R&D, Raritan, NJ, USA, 9 Legend Biotech USA, Inc., Piscataway, NJ, USA, 10 Janssen R&D, Beerse, Belgium, 11 Janssen R&D, Spring House, PA, USA, 12 Universitätsklinikum Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany, 13 Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA Co n text: Cilta-cel, a chimeric antigen receptor T (CAR-T) cell therapywith twoB-cell maturation antigen (BCMA)-targeting single- domain antibodies demonstrated efficacy in relapsed/refractory multiple myeloma (MM). Objecti v es: To describe mitigation and management strategies to identify and reduce the risk for neurologic adverse events (AEs). D esig n : CARTITUDE-2 (NCT04133636) is an ongoing phase 2, multi-cohort, open-label study. Patie n ts a n d Other Participa n ts: Patients had progressive MM per IMWG criteria, measurable disease, ECOG  1, received 1−3 prior lines of therapy (including PI and IMiD), and were lenalidomide refractory (no prior BCMA-targeting agent). I n ter v e n tio n s: Cilta-cel (target dose: 0. 7 5×10 6 [0.5–1.0×10 6 ] CAR+ viable T cells/kg) was given as a single infusion after lymphodepletion (cyclophosphamide 300 mg/m 2 + fludarabine 30 mg/m 2 ). Monitoring and mitigation of neurologic AEs included effective bridging therapy to reduce tumor burden prior to lymphodepletion, assessment of CAR-T-related immune effector cell-associated neurotoxicity syndrome (ICANS) using an ICE tool, handwriting assessments, and neuroimaging and electroencephalogram for prior neurologic disease patients. Management of neurologic AEs included evaluating infectious and paraneoplastic etiologies with ICANS  grade 1, administration of tocilizumab (if concurrent CRS, all grades of ICANS), and/or dexamethasone (grade 2/3) or methylprednisolone (grade 4). Mai n Outco m es Measures: ICANS and CRS were graded by ASTCT criteria; non-ICANS neurotoxicities were graded per CTCAE v5.0. Results: As of 15 Jan 2021 (median follow-up: 5.8 months), 20 patients in Cohort A (median age: 60 years; 65% males) received cilta-cel. Four patients (20%) had neurotoxicities. Three patients had ICANS (grade 1/2); median time to onset of symptoms: 8 days ( 7 –11) and median duration: 2 days (1–2). Supportive measures, including levetiracetam and steroids, were received by 2/3 patients; all 3 had concurrent CRS and all recovered. One patient developed isolated facial paralysis (grade 2; onset: Day 29 after cilta-cel infusion; recovery: 51 days after the onset; treatment: dexamethasone for 28 days). Co n clusio n s: Neurologic AEs were generally manageable in patients with MM following cilta-cel treatment. No movement or neurocognitive disorders were observed in patients from Cohort A. Early detection and management of neurologic AEs can lead to better treatment outcomes. Ack n owledge m e n ts: The study was funded by Janssen Research & Development, LLC and Legend Biotech, Inc. Keywords: MM, CAR-T, ciltacabtagene autoleucel, multiple myeloma, neurotoxicity MM-119 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) Saad Z. Usmani 1 *, Jesus G. Berdeja 2 , Deepu Madduri 3 , Andrzej Jakubowiak 4 , Mounzer Agha 5 , Adam D. Cohen 6 , Parameswaran Hari 7 , Tzu-Min Yeh 8 , Yunsi Olyslager 9 , Arnob Banerjee 10 , Carolyn C Jackson 8 , Alicia Allred 10 , Enrique Zudaire 10 , William Deraedt 9 , Xiaoling Wu 11 , Marlene J. Carrasco-Alfonso 11 , Muhammad Akram 11 , Yi Lin 12 , Thomas Martin 13 , Sundar Jagannath 3 1 Levine Cancer Institute-Atrium Health, Charlotte, NC, USA, 2 Sarah Cannon Research Institute, Nashville, TN, USA, 3 Mount Sinai Medical Center, New York, NY, USA, 4 University of Chicago, Chicago, IL, USA, 5 UPMC Hillman Cancer Center, Pittsburgh, PA, USA, 6 Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA, 7 Medical College of Wisconsin, Milwaukee, WI, USA, 8 Janssen R&D, Raritan, NJ, USA, 9 Janssen R&D, Beerse, Belgium, 10 Janssen R&D, Spring House, PA, USA, 11 Legend Biotech USA, Inc, Piscataway, NJ, USA, 12 Mayo Clinic, Rochester, MN, USA, 13 UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA Co n text: Cilta-cel, a CAR-T cell therapy containing 2 BCMA- targeting single domain antibodies designed to confer high avidity binding, is being evaluated in the CARTITUDE-1 phase 1b/2 study. Objecti v es: Provide updated results with a longer duration (median 12.4 months) of follow-up . Patie n ts or Other Participa n ts: Patients had RRMM, measurable disease,  3 prior regimens (or double refractory to proteasome inhibitor and immunomodulatory drug) and received anti-CD38. I n ter v e n tio n s: A single cilta-cel infusion at the targeted dose of 0. 7 5×10 6 (0.5–1.0×10 6 ) CAR+ viable T cells/kg was infused after cyclophosphamide/fludarabine lymphodepletion. Mai n Outco m es Measures: The primary objectives were characterization of cilta-cel safety and confirmation of recommended phase 2 dose (phase 1b) and evaluation of efficacy (phase 2). Cytokine release syndrome (CRS) was graded by Lee 2014 and neurotoxicity by CTCAE in phase 1b; both were graded by ASTCT criteria in phase 2. Lee 2014 and CTCAE grading were mapped to ASTCT criteria for CRS and ICANS, respectively. Response was assessed per IMWG criteria. Results: At 12.4-month median follow-up, 9 7 patients (median of 6 prior lines) received cilta-cel. Overall response rate was 9 7 % (95% CI, 91–99), and 6 7 % had stringent complete response (sCR). Median time to first response was 1 month (range, 1–9), median time to  CR was 2 months (range, 1–15), and median duration of response was not reached. Of 5 7 minimal residual disease (MRD)-evaluable patients, 93% were MRD-negative at 10 –5 . The 12-month progression-free survival (PFS) and overall survival rates (95% CI) were 77 % (66–84) and 89% (80–94), respectively; median PFS was not reached. Grade 3/4 hematologic AEs included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred