B- Cell Maturation Antigen (BCMA) Re-Emergence and Relapse Patterns Post-BCMA-Chimeric Antigen Receptor T Cell (CAR-T ) Therapy for Multiple Myeloma

INTRODUCTION:

The outcomes of patients (pts) with triple and Penta-class relapsed refractory multiple myeloma (RRMM) are poor. The first B- cell maturation antigen (BCMA) chimeric antigen receptor T cell (CAR-T) therapy in RRMM was FDA approved in March 2021. The overall response rate (ORR) was 73%, with median progression-free survival (PFS) and median overall survival (OS) of 8.8 and 19.4 months, respectively. Undetectable soluble sBCMA levels correlated with the depth of responses, and re-emergence of sBCMA level indicates relapse. Our goal is to evaluate BCMA re-emergence on plasma cells in bone marrow samples using multiparameter flow cytometry (MFC) and correlation with outcome.

METHODS:

19 pts who received BCMA CAR-T therapy for RRMM at the University of Kansas Health System between May 2021 and June 2022 were included in the study. Those with less than 3 months of follow-up were excluded from the analysis. Only patients with established negative BCMA on BMBx at day 30 were included. All patients had standard restaging BMBx at 1 mo., 3 mo., 6 mo., and 1 yr. Eight-color MFC was performed on the BMBx specimens. BCMA antibody was purchased from R & D Systems (Minneapolis, MN). Data analysis was performed using FCS Express 5 software (De Novo Software, Los Angeles, CA). 500,000 to up to 2,000,000 events were acquired in all the cases. Responses were evaluated using the International Myeloma Working Group (IMWG) criteria. Kaplan-Meier analyses were used to estimate PFS. Time to BCMA re-emergence was defined as the time from CAR-T cell infusion to positive BCMA on BM PC.

RESULTS: Demographic data for 19 RRMM BCMA CAR-T recipients is shown (Table 1). The groups were similar except for higher non-osseous extramedullary disease in the relapsed group. The median follow-up was 9 mo. (3-12 mo.). Nine patients (47.3%) relapsed and ten (52.6%) did not. The median time to relapse was 5 mo. (2 to 12 mo.). BCMA re-emergence was demonstrated in a total of 10 patients (52.6%). Of these, 7 (70%) clinically relapsed and 3 (30%) did not. The median time to BCMA re-emergence was 3 mo. (2-12 mo.). Amongst the nine patients who relapsed, 7 patients (77.7%) demonstrated BCMA re-emergence, of which 5 patients (55.5%) had BCMA re-emergence prior to clinical relapse (Figure1). The median time from BCMA re-emergence to clinical relapse in those 5 patients was 2 mo. (0-7 mo.) Amongst the 10 patients with no relapse, only 3 (30%) demonstrated BCMA re-emergence.

CONCLUSIONS:

Re-emergence of BCMA after BCMA-directed CAR-T therapy as detected by MFC on BMBx may be a prognostic marker and correlate with responses. Although there was a higher incidence of BCMA re-emergence in the relapsed group, no significant differences were observed due to the small sample size. This warrants further investigation. Prospective studies are needed to evaluate the correlation between BCMA re-emergence with prognosis and prediction of relapse.

Hoffmann:Kite: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria; AstraZeneca: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Novartis: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria. Abhyankar:Therakos: Consultancy, Research Funding, Speakers Bureau; Incyte: Consultancy, Research Funding, Speakers Bureau. McGuirk:BMS: Consultancy, Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria; Nextar: Consultancy, Honoraria; Orca Bio: Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau; Juno Therapeutics: Consultancy, Honoraria, Research Funding; Allovir: Consultancy, Honoraria, Research Funding, Speakers Bureau; Magenta Therapeutics: Consultancy, Honoraria, Research Funding; Sana: Honoraria; CRISPR Therapeutics: Consultancy; In8bio, Inc.: Other: IIT Clinical Trial.