Novel Predictive Model May Provide Strategic Insights for CAR T-Cell Therapy for Patients With R/R MM

The myeloma CAR T Relapse (MyCARe) model, a novel prognostic model, may be useful in strategizing optimal timing of chimeric antigen receptor (CAR) T-cell therapy among certain subgroups of patients with relapsed/refractory (R/R) multiple myeloma (MM), according to an international, retrospective, observational study, which also observed that outcomes after CAR T-cell therapy are comparable between Europe and the United States.

Eligibility for this study included patients with R/R MM who were treated with currently available commercial or academically produced anti–B-cell maturation antigen (BCMA) CAR T-cell therapy. Investigators evaluated 136 patients from Europe and 133 patients from the United States. This simple prediction model, titled the Myeloma CAR T Relapse (MyCARe)] model was built in the European training cohort and externally validated in the US cohort. The model was then tested within patient- and treatment-specific subgroups. The MyCARe model has the possibility to predict early relapse, response, and survival. The main end points of this study were relapse and overall efficacy.

Concluding data demonstrated that the overall response rate (ORR) was 87% and comparable between both cohorts, and complete responses (CR) were seen in 48% (Europe) and 49% (United States). The median time to relapse was 5 months, and early relapse <5 months from infusion exhibited poor survival across cohorts, with the 12-month OS of 30% (Europe) and 14% (United States). It was determined that the 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.

Each of these factors received 1 point, which formed the 3-tiered MyCARe model: scores 0-1 measured at low risk, scores 2-3 at intermediate risk, and a score of 4 at high risk. The MyCARe model was notably associated with a distinct 5-month incidence of relapse/progression (P < .001): 7% for low-risk, 27% for intermediate-risk, and 53% for high-risk groups. This model was validated in the US cohort and maintained prognostic utility for response, survival, and outcomes across subgroups.

Safety evaluations measured that grades >2 of cytokine release syndrome (CRS) were similar and occurred in 7% (10 patients) in the European cohort and 5% (7 patients) in the United States cohort. 

No CRS was observed in 8% and 23% of patients, respectively. It was noted that severe immune effector cell-associated neurotoxicity syndrome (ICANS) of grade >2 occurred in 1% (1 patient) in the European cohort and 7% (10 patients) in the United States cohort. The use of tocilizumab was similar between cohorts (56% Europe vs 61% the United States; P = .59). Additionally, the rates of CRS and ICANS were significantly different between both cohorts (P < .001, respectively), which was influenced by the type of CAR T-cell product (P < .001, respectively). Investigators noted that despite growing advancements in R/R MM treatment, most patients will experience relapse, even after CAR T-cell therapy.

Nico Gagelmann, MD, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, and colleagues concluded, “We observed comparable efficacy and toxicity between Europe and US cohorts. Early relapse within 5 months from infusion was significantly associated with very poor outcomes.”

“The MyCARe model may facilitate optimal timing of CAR-T cells in patient-specific subgroups,” they explained.

Source:

Gagelmann N, Dima D, Merz M, et al. Development and validation of a prediction model of outcome after B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy in relapsed/refractory multiple myeloma. JCO, JCO.23.02232. doi:10.1200/JCO.23.02232