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1973 In Vivo Anti-BCMA CAR T-Cell Expansion Kinetics Correlate with Early IMWG Response in RRMM: A Single Institution Study with Comparative Analysis of Idecabtagene Vicleucel and Ciltacabtagene Autoleucel

Program: Oral and Poster Abstracts
Session: 652. Multiple Myeloma: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Research, Fundamental Science, Translational Research, Clinical Research, real-world evidence
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Mehmet H. Kocoglu, MD1,2, Aaron P. Rapoport, MD3, Tim Luetkens, MD3,4*, Etse Gebru, BS3*, Destiny Omili3*, Jean A. Yared, MD5, Nancy M. Hardy, MD6,7, Soren M Bentzen, PhD8*, Ashraf Z. Badros, MD9,10 and Djordje Atanackovic, MD3

1University of Maryland Marlene and Stewart Greenebaum Comprehensive Cancer Center, Baltimore, MD
2Marlene and Stewart Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD
3University of Maryland Greenebaum Comprehensive Cancer Center, Baltimore, MD
4Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD
5University of Maryland Marlene and Stewart Comprehensive Cancer Center, Baltimore, MD
6University of Maryland Medical Center, Baltimore, MD
7University of Maryland School of Medicine, Baltimore, MD
8Division of Biostatistics and Bioinformatics, Baltimore, USA, University of Maryland School of Medicine, Baltimore, MD
9University of Maryland Greenebaum Cancer Center, Baltimore, MD
10Greenebaum Comprehensive Cancer Center, University of Maryland School of Medicine, Baltimore, MD

Introduction: The most recent breakthrough in the treatment of relapsed/refractory MM (RRMM) is chimeric antigen receptor (CAR) T-cell (CAR T) therapy which led to high overall response rates with acceptable toxicity. Here we present our single-institution experience with MM-specific CAR T performing a comparative analysis of clinical data and expansion kinetics after infusion of two commercially available myeloma CAR-T products.

Methods: Out of 76 RRMM patients treated with CAR T, 23 patients provided consent, enrolled, apheresed and treated with commercial CAR-T between 6/20/2022 and 4/24/2023. Majority of patients had relapsed and multi-refractory MM. 11 patients received idecabtagene (idecel) and 12 received ciltacabtagene (ciltacel). Manufacturing slot availability was the primary deterministic factor for CAR T-type assignment. Study was IRB approved and informed consent was obtained to collect blood and clinical data. Blood samples were obtained at apheresis, pre-lymphodepleting (LD) chemotherapy, and on days 0, +7, +14, +21, +28 and +3 months post CAR T-cell infusion. PBMCs were generated from whole blood using density gradient centrifugation and were stained using BCMA or control CAR detection reagents and monoclonal antibodies against T-cell surface antigens. Samples were analyzed using MacsQuant-10 flow cytometer, gating on CD3+ and CAR+ cells. Fisher’s Exact Test and Pearson Chi-Square tests were used for assessment of categorical variables whereas Independent-Samples Median Test was employed for non-categorical variables. Mann-Whitney U test was used for CAR T cell expansion analyses at individual timepoints.

Results: As of July 10, 2023, 23 commercial patients were enrolled. Baseline clinical characteristics were comparable between the idecel and ciltacel cohorts with regard to age (median 66, p=0.827), prior lines of treatment, ASCT history (Table 1). Two patients in each cohort were penta-refractory. Three patients in each cohort had EMD (27.3%). There was balanced distribution of del 17p and t(4;14) across cohorts (p=1.000, p=0.175). Each cohort had 1 RISS-3 patient (p=0.476). Seven patients (30.4%) were previously treated with belantamab. Pre-apheresis and pre-LD absolute lymphocyte count (ALC) were comparable across cohorts. (Table 1). There were no G3 CRS events whereas G1/2 CRS events were not statistically significant between cohorts (p=0.256). Three G3 ICANS were observed, 2 in idecel and 1 in ciltacel cohorts (18.2% and 8.3%). Distribution of all-grade ICANS across cohorts were not statistically significant (p=0.676). Post-CAR T ferritin max correlated with the baseline b2m (p<0.001) and tocilizumab dose number (p=0.009) but none correlated with peak CAR T expansion (p=0.315). Responses were assessed by IMWG criteria at months 1,3,6,9 for efficacy-evaluable patients at that timepoint (n=19,14,8 and 2 in grand cohort (82.6%, 60.9%, 34.8% and 8.7%)). Global cohort ORR was 78.3% (n=18) and 60.9% (n=14) at days 30 and 90 respectively. +1 month IMWG responses were comparable with 72.7% (8/11) in idecel and 83.3% (10/12) in ciltacel cohort (p=0.625). Similarly, there was no statistically significant ORR difference between cohorts at 3, 6, and 9 months. Two-way ANOVA revealed a trend towards an effect of treatment type on CAR-T expansion (p=0.0595) (Figure 1A). Time-to-peak analysis reached statistical significance (p=0.0127) between two products (Figure 1B). Despite its delayed peak, ciltacel had significantly higher magnitude of expansion (p=0.043) (Figure 1C). Peak CAR-T expansion was associated with clinical responses across cohorts at +1 (p=0.034) and +3 months (p=0.050) but not at +6 months (p=0.449). Day +30 responses were indicative of Day +90 and Day +180 responses (p<0.001, p=0.011).

Conclusions: In our single-center study of comparative analysis of commercial BCMA targeting CAR T-cell treatments, peak CAR T-cell expansion showed a positive correlation with +1 and +3 month post-CAR-T clinical responses. Despite the delayed peak expansion with ciltacel, the expansion was more robust with a higher level of circulating CAR T-cells. Baseline ALC or fludarabine dose reduction did not have an impact on overall CAR T expansion in combined cohort. Studies are underway at our institution investigating anti-BCMA CAR T cell responses in more detail and larger numbers of patients and functional studies will be further presented.

Disclosures: Yared: University of Maryland: Current Employment; Sanofi, Incyte, Kadmon, Omeros: Consultancy; Institution research funding as a PI on pharma- sponsored clinical trials opened at the University of Maryland: Research Funding; AAACTT (Board of Directors), NHLBI DSMB (Board member): Membership on an entity's Board of Directors or advisory committees. Hardy: Kite/Gilead: Membership on an entity's Board of Directors or advisory committees; InCyte Corporation: Membership on an entity's Board of Directors or advisory committees; American Gene Technologies: Other: Member DSMB. Badros: BMS: Research Funding; Janssen: Research Funding; GSK: Research Funding.

*signifies non-member of ASH