Validation and refinement of the new Consensus Genomic Staging (CGS) of high-risk multiple myeloma (HRMM) in relapsed and refractory patients treated with BCMA CAR-T.

The new Consensus Genomic Staging (CGS) of high-risk multiple myeloma (MM) was recently updated by the International Myeloma Society and International Myeloma Working Group. We performed a retrospective study to validate the revised HRMM criteria in relapsed and refractory MM patients treated with BCMA CAR-T. A total of 158 patients were included, of whom 75 (47%) met criteria for HRMM. The median follow-up was 24.8 months (95% CI 22.5-30.3). On multivariable analysis, patients with HRMM had significantly shorter PFS (HR 1.89, p = 0.003) and OS (HR 3.06, p < 0.001) compared to standard-risk MM (SRMM) following BCMA CAR-T. LDH > 210 U/L and EMD were also identified as independent adverse risk factors. Based on survival analyses, we constructed a reclassified staging system incorporating LDH and EMD into the CGS-HRMM criteria. Patients were divided into four discrete risk groups: low risk (SRMM with normal LDH and no EMD; n = 42, 26%), intermediate-low risk (HRMM with normal LDH and no EMD; n = 31, 20%), intermediate-high risk (SRMM with high LDH, EMD, or both; n = 41, 26%), and high risk (HRMM with high LDH, EMD, or both; n = 44, 28%). Patients with low, intermediate-low, intermediate-high, and high-risk disease had a median PFS of 35.0, 19.6, 10.4, and 6.6 months, respectively (p < 0.0001), and an estimated 24-month OS of 90%, 69%, 66%, and 26%, respectively (p < 0.0001). In summary, we validated the new CGS-HRMM criteria in relapsed and refractory MM patients treated with BCMA CAR-T. We also propose a reclassified staging system to further improve risk stratification in MM patients treated with BCMA CAR-T.