TREATMENT OF RELAPSED/REFRACTORY MULTIPLE MYELOMA WITH JNJ-4528, A B-CELL MATURATION ANTIGEN (BCMA)-DIRECTED CHIMERIC ANTIGEN RECEPTOR (CAR)-T CELL THERAPY: UPDATE OF PHASE 1B RESULTS FROM CARTITUDE-1
Author(s): ,
Saad Z. Usmani
Affiliations:
Levine Cancer Institute - Atrium Health,Charlotte,United States
,
Deepu Madduri
Affiliations:
Mount Sinai Medical Center,New York,United States
,
Jesus G. Berdeja
Affiliations:
Sarah Cannon Research Institute,Nashville,United States
,
Indrajeet Singh
Affiliations:
Janssen R&D,Spring House,United States
,
Enrique Zudaire
Affiliations:
Janssen R&D,Spring House,United States
,
Tzu-Min Yeh
Affiliations:
Janssen R&D,Raritan,United States
,
Alicia J. Allred
Affiliations:
Janssen R&D,Spring House,United States
,
Yunsi Olyslager
Affiliations:
Janssen R&D,Beerse,Belgium
,
Arnob Banerjee
Affiliations:
Janssen R&D,Spring House,United States
,
Jenna D. Goldberg
Affiliations:
Janssen R&D,Raritan,United States
,
Jordan M. Schecter
Affiliations:
Janssen R&D,Raritan,United States
,
Dong Geng
Affiliations:
Legend Biotech USA Inc.,Piscataway,United States
,
Xiaoling Wu
Affiliations:
Legend Biotech USA Inc.,Piscataway,United States
,
Marlene J. Carrasco-Alfonso
Affiliations:
Legend Biotech USA Inc.,Piscataway,United States
,
Syed Rizvi
Affiliations:
Legend Biotech USA Inc.,Piscataway,United States
,
Frank Fan
Affiliations:
Nanjing Legend Biotech,Nanjing,China
,
Andrzej Jakubowiak
Affiliations:
University of Chicago,Chicago,United States
Sundar Jagannath
Affiliations:
Mount Sinai Medical Center,New York,United States
EHA Library. Usmani S. 06/12/20; 294843; EP926
Prof. Dr. Saad Usmani
Prof. Dr. Saad Usmani
Contributions
Abstract

Abstract: EP926

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
JNJ-68284528 (JNJ-4528) is a CAR-T cell therapy containing two BCMA-targeting single-domain antibodies designed to confer avidity. CARTITUDE-1 (NCT03548207) is a phase 1b/2 study of JNJ-4528 in patients with relapsed and/or refractory multiple myeloma.

Aims
To present updated safety and efficacy results from the phase 1b portion of CARTITUDE-1 with longer follow-up.

Methods
Patients were diagnosed with multiple myeloma per International Myeloma Working Group (IMWG) criteria, had measurable disease, received ≥3 prior regimens (or were double refractory to a proteasome inhibitor and an immunomodulatory drug), and received an anti-CD38 antibody. All patients provided informed consent. Bridging therapy was allowed after apheresis. Patients were administered a lymphodepleting regimen of cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 over 3 days. JNJ-4528 was administered as a single infusion (median dose of 0.73x106 CAR+ viable T cells/kg [range, 0.5–0.9]). Cytokine release syndrome (CRS) was graded using Lee et al. criteria (Blood 2014;124:188), and neurotoxicity was graded per Common Terminology Criteria for Adverse Events (v5.0) and American Society for Transplantation and Cellular Therapy criteria (Lee et al. Biol Blood Marrow Transplant 2019 25(4):625). Response was assessed by an independent review committee per IMWG criteria.

Results
As of January 17, 2020, median duration of follow-up was 9 months (range, 3–17). Phase 1b enrollment is complete (N=29 treated; median 5 [range, 3–18] prior lines, 76% penta-exposed, 86% triple-refractory, 31% penta-refractory, 97% refractory to last line of therapy). Most frequent adverse events (AEs) of any grade were neutropenia (100%), CRS (93%), and thrombocytopenia (93%). Grade ≥3 hematologic AEs were neutropenia (100%), thrombocytopenia (69%), and leukopenia (59%). Among 27 (93%) patients with CRS, most had low grade events; one grade 3 event and one grade 5 event (on day 99 subsequent to dose-limiting toxicity of prolonged grade 4 CRS) were also reported. Median time to onset of CRS was 7 days (range, 2–12). Four patients had treatment-related neurotoxicity: three grade 1–2 and one grade 3.

The overall response rate was 100%, with 22 (76%) stringent complete responses (sCRs), six (21%) very good partial responses (VGPRs), and one (3%) partial response. Median time to complete response was 2 months (range, 1–9). At data cut-off, 26 (90%) of 29 patients were progression-free, with 6-month progression-free survival rate of 93% and longest response ongoing at 15 months. Two patients died during the study: one due to CRS and one due to acute myeloid leukemia (not treatment-related). All 16 patients (14 sCR, 2 VGPR) evaluable at 6 months were minimal residual disease negative at 10-5 or 10-6 level of sensitivity.

JNJ-4528 CAR+ T cell expansion peaked between day 10–14. At 6-month individual follow-up, JNJ-4528 CAR+ T cells in peripheral blood were below the level of quantification (2 cells/µL) in 22/28 patients, suggesting that CAR-T persistence did not seem to correlate with deepening of response. At peak CAR-T cell expansion, preferential expansion of CD8+ CAR-T cells with a central memory phenotype was observed in peripheral blood.

Conclusion
All patients treated with JNJ-4528 had responses. The responses were early, deep, and durable at a low dose of CAR-T cells, with 26/29 (90%) patients progression free at median 9-month follow-up. In most patients, CRS was manageable, with the relatively late median day 7 onset supporting outpatient dosing.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Multiple myeloma

Abstract: EP926

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
JNJ-68284528 (JNJ-4528) is a CAR-T cell therapy containing two BCMA-targeting single-domain antibodies designed to confer avidity. CARTITUDE-1 (NCT03548207) is a phase 1b/2 study of JNJ-4528 in patients with relapsed and/or refractory multiple myeloma.

Aims
To present updated safety and efficacy results from the phase 1b portion of CARTITUDE-1 with longer follow-up.

Methods
Patients were diagnosed with multiple myeloma per International Myeloma Working Group (IMWG) criteria, had measurable disease, received ≥3 prior regimens (or were double refractory to a proteasome inhibitor and an immunomodulatory drug), and received an anti-CD38 antibody. All patients provided informed consent. Bridging therapy was allowed after apheresis. Patients were administered a lymphodepleting regimen of cyclophosphamide 300 mg/m2 + fludarabine 30 mg/m2 over 3 days. JNJ-4528 was administered as a single infusion (median dose of 0.73x106 CAR+ viable T cells/kg [range, 0.5–0.9]). Cytokine release syndrome (CRS) was graded using Lee et al. criteria (Blood 2014;124:188), and neurotoxicity was graded per Common Terminology Criteria for Adverse Events (v5.0) and American Society for Transplantation and Cellular Therapy criteria (Lee et al. Biol Blood Marrow Transplant 2019 25(4):625). Response was assessed by an independent review committee per IMWG criteria.

Results
As of January 17, 2020, median duration of follow-up was 9 months (range, 3–17). Phase 1b enrollment is complete (N=29 treated; median 5 [range, 3–18] prior lines, 76% penta-exposed, 86% triple-refractory, 31% penta-refractory, 97% refractory to last line of therapy). Most frequent adverse events (AEs) of any grade were neutropenia (100%), CRS (93%), and thrombocytopenia (93%). Grade ≥3 hematologic AEs were neutropenia (100%), thrombocytopenia (69%), and leukopenia (59%). Among 27 (93%) patients with CRS, most had low grade events; one grade 3 event and one grade 5 event (on day 99 subsequent to dose-limiting toxicity of prolonged grade 4 CRS) were also reported. Median time to onset of CRS was 7 days (range, 2–12). Four patients had treatment-related neurotoxicity: three grade 1–2 and one grade 3.

The overall response rate was 100%, with 22 (76%) stringent complete responses (sCRs), six (21%) very good partial responses (VGPRs), and one (3%) partial response. Median time to complete response was 2 months (range, 1–9). At data cut-off, 26 (90%) of 29 patients were progression-free, with 6-month progression-free survival rate of 93% and longest response ongoing at 15 months. Two patients died during the study: one due to CRS and one due to acute myeloid leukemia (not treatment-related). All 16 patients (14 sCR, 2 VGPR) evaluable at 6 months were minimal residual disease negative at 10-5 or 10-6 level of sensitivity.

JNJ-4528 CAR+ T cell expansion peaked between day 10–14. At 6-month individual follow-up, JNJ-4528 CAR+ T cells in peripheral blood were below the level of quantification (2 cells/µL) in 22/28 patients, suggesting that CAR-T persistence did not seem to correlate with deepening of response. At peak CAR-T cell expansion, preferential expansion of CD8+ CAR-T cells with a central memory phenotype was observed in peripheral blood.

Conclusion
All patients treated with JNJ-4528 had responses. The responses were early, deep, and durable at a low dose of CAR-T cells, with 26/29 (90%) patients progression free at median 9-month follow-up. In most patients, CRS was manageable, with the relatively late median day 7 onset supporting outpatient dosing.

Session topic: 14. Myeloma and other monoclonal gammopathies - Clinical

Keyword(s): Multiple myeloma

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