Development and validation of a prediction model of outcomes with BCMA-directed CAR-T for relapsed or refractory multiple myeloma

Although CAR-T cells are an established therapy for relapsed or refractory multiple myeloma (RRMM), there are no established models predicting outcomes to identify patients who may benefit the most from CAR-T. A retrospective observational study included 136 European BCMA-directed CAR-T treated RRMM patients in a training cohort and 133 US patients in a validation cohort. The overall response rate was 87% and comparable between Europe and the US. Median time to relapse was 5 months, and early relapse (< 5 months from infusion) was associated with poor 12-month survival (30% in Europe and 14% in the US). Presence of extramedullary disease or plasma cell leukemia, lenalidomide-refractoriness, high-risk cytogenetics, and increased ferritin at the time of lymphodepletion were independent predictors of early relapse or progression. In the MyCARe model, each of these factors received one point, with low-risk at scores 0-1, intermediate risk at scores 2-3, and high-risk at score 4. The 5-month incidence of relapse or progression in Europe was 7% in the low-risk group, 27% in the intermediate-risk group, and 53% in the high-risk group (p<0.001). The model was validated in the US cohort. The authors conclude that MyCARe could identify patients who benefit the most from CAR-T.