P19: BASELINE CORRELATES OF COMPLETE RESPONSE TO IDECABTAGENE VICLEUCEL (IDE-CEL, BB2121), A BCMA-DIRECTED CAR T CELL THERAPY IN PATIENTS WITH RELAPSED AND REFRACTORY MULTIPLE MYELOMA: SUBANALYSIS OF THE KARMMA TRIAL
Authors: P Rodríguez-Otero, N Shah, N Munshi, J Berdeja, S Jagannath, O Finney, N Martin, A Agarwal, E Rowe, T Campbell, J San-Miguel
Journal: HemaSphere (2022)

Introduction: In the pivotal phase 2 KarMMa trial (NCT03361748), in heavily pretreated RRMM, 33% of patients (pts) who received ide-cel, a B-cell maturation antigen (BCMA)-directed CAR T cell therapy, had complete response (CR) or stringent CR (sCR), with a median duration of response of 21.5 months (Anderson et al. ASCO 2021. Poster 8016). This subanalysis aimed to identify baseline correlates of pts attaining CR/sCR in KarMMa. Methods: Pts with ≥3 prior lines of therapy (including an immunomodulatory agent, proteasome inhibitor, and anti-CD38 antibody), and MM refractory to last regimen per IMWG criteria received ide-cel infusion (target doses 150–450 x 106 CAR+ T cells) after lymphodepletion. Bridging therapy was optional. Endpoints included overall response rate (primary) and CR/sCR rate (key secondary). Baseline characteristics were collected prior to lymphodepletion and for select biomarkers on day of infusion. Univariate and multivariate logistic regression models were used to identify baseline characteristics correlating with the likelihood of achieving CR/sCR. Results: Of 128 pts who received ide-cel (data cutoff Dec 21, 2020), 42 pts achieved CR/sCR and 86 had non-CR/sCR (very good partial response, partial response, or no response). In pts with CR/sCR, 32 (76%) were negative for minimal residual disease (MRD) (sensitivity level of <10-5) and 19 maintained MRD negativity at 12-mo follow-up. Baseline characteristics were generally balanced between pts with CR/sCR and non-CR/sCR; notable exceptions included revised International Staging System (ISS) stage III disease, IgG chain type, CD138+ plasma cell percentage, and β-2-microglobulin levels (Table). Univariate analysis of CR/sCR by baseline characteristics showed that IgG heavy chain versus other heavy chain types (odds ratio [OR]: 0.162, P<0.0001), high sBCMA (OR: 0.646, P=0.0007), β-2-microglobulin (≥5.5 vs <3.5 mg/L; OR: 0.201, P=0.0072), and presence of extramedullary disease (OR: 0.428, P=0.0394) were negatively associated with CR/sCR, whereas high vector copy number in drug product was positively associated with CR/sCR (OR: 1.290, P=0.0287). Multivariate analysis of CR/sCR identified IgG heavy chain versus other heavy chain types (OR: 0.100, P<0.0001), high sBCMA (OR: 0.637, P=0.0110), and elevated prothrombin time-international normalized test (PT-INR) (OR: 0.005, P=0.0365) as negative correlates of CR/sCR, and high vector copy number in drug product (OR: 1.486, P=0.0168) as a positive correlate of CR/sCR. Descriptive analysis demonstrated lower median (range) sBCMA levels at baseline in pts with CR/sCR (191 ng/mL [11–909]) versus non-CR/sCR (340 ng/mL [19–2735]); across both groups, sBCMA levels had increased from screening (CR/sCR, 161 ng/mL [27–689]; non-CR/sCR, 302 ng/mL [24–1490]). Conclusions: In this subanalysis of KarMMa, multivariate analysis identified IgG, sBCMA, and PT-INR as negative correlates of CR/sCR, and vector copy number in drug product a positive correlate. As sBCMA is a tumor burden indicator and can affect BCMA-targeted therapies (Cowan et al. ASH 2019. Abstract 204), selecting pts with lower tumor burden and controlling tumor burden during manufacturing or bridging therapy may aid in achieving CR/sCR with ide-cel. Previously presented and published: Shah N, et al. ASH 2021, Blood 2021; 138:1739. Study support: 2seventy bio, formerly bluebird bio, and Celgene, a Bristol-Myers Squibb Company.